The MS Relapse is Not So Inexpensive

Friends, you may recall in March that I found myself in the mist of a multiple sclerosis relapse, no matter how hard I tried to wish it away. The time had come to Join the MS Party. You know the routine.

First, you call your MS nurse (or doctor's liaison) to explain your symptoms.

"Ok, tell me. What's going on?" Well, my left arm, fingers to upper back, has gone numb again and is getting weaker. My legs are weak and shake when I've been standing, like while rinsing dishes. And I've been having trouble getting up from a chair or the couch, so I've been pulling on the coffee table to help get up.

"How long has this been going on?" I've been having problems with my legs since about January. I thought it had something to do with the Rheumatoid Arthritis. The shaking just got really noticeable about two weeks ago. Oh, and I'm lilting to the left.

"Any falls?" No, but I'm bumping into things and not really walking in a straight line. And kinda hugging the wall on my stairs.

"How's your bladder?" No problems. I don't think there's a UTI.

"How are your eyes?" They seem fine actually. Colors look equal. But my ears have been ringing loudly again and are sensitive to sound.

"I think you need to come in." Yeah, I knew you'd say that.

Second, the doctor's visit during which you explain all of the above and go through the standard neurological dog tricks, er, I mean exam.

"Yep, you are experiencing a relapse. We'll start you on a 5-day round (IV Solumedrol which is intravenously-delivered, mega-doses of steroids) today. Do you have to be anywhere right now?" No, I knew I'd be getting hooked up today. I even brought a book to read.

"Oh, good. You came prepared." That's me, always prepared.

So I have finally received all the EOBs related to this visit, the 5-day IVSM, and the two follow-up visits which occurred in April and May. Here's the overview.

• Original charges billed to Insurance: $4535.40


• Charges disallowed by Insurance: $3551.91


• Amount paid by Insurance: $ 784.24


• Amount paid by Patient (OOP): $ 199.25

In April it was time to Surf the Magnetic Tube, ie. get MRIs conducted of brain and cervical spine. It had been 15 months since my last run through the machine and we needed a good picture to know if a change in Disease Modifying Drug was needed.

• Original charges billed to Insurance: $6017.00


• Charges disallowed by Insurance: $1002.85


• Amount paid by Insurance: $ 4513.04


• Amount paid by Patient (OOP): $ 501.41

In a follow-up visit, we discussed the results of the MRIs. A pretty picture of the new 3cm lesion in my cervical spine can be found in Sometimes Going with the Flow Isn't Easy. The good news is that with the addition of Baclofen, I have regained some freedom of movement. Yippee.

Now keep in mind that while my out-of-pocket was $700.66, I also missed two weeks of work without the possibility of paid leave. As a self-employed person, with somewhat seasonal fluctuations in work opportunity, that makes a huge dent in my income while normal expenses continue to accrue.

Fortunately years ago, I chose an insurance policy with a small 10% coinsurance level. If I had chosen to go with a lower premium but larger 20% coinsurance, my cost would have been $1226.32. With a 30% coinsurance, my cost would have been $1751.98. If I had had a high-deductible policy, the kind which President Bush and others have been encouraging, my out-of-pocket cost would have been a whopping $5997.94 for the treatment of one exacerbation and one trip through the MRI machine.

Who ever said MS was inexpensive? Nobody I know.

Carnival Submissions Due

This week's theme is Independence. Please interpret the word any way you wish in relationship to some aspect of your life.

Just a reminder that submissions for this week's Carnival of MS Bloggers are due Tuesday morning, July 1, 2008!! You may submit a recent post from your blog via blogcarnival or email.

I look forward to seeing what great stuff you wish to share. Thank you.

Cranky Baby and Yamaha meet at the Bench

Shauna sent this great photo of Cranky Baby at the Grandfolks' house. I don't know about you, but I think that Cranky Baby doesn't look so cranky here. It must be the thrill of accomplishment from sitting at such a beautiful musical instrument. Everybody KNOWS that music has the power to calm the wild beast.

I'm so proud. Makes me feel like a Cranky Auntie.

The Bioentrepreneur and Fampridine

What is a bioentrepreneur?

The term, when used loosely, describes the scientist who boldly decides to take his research from the lab, patent his findings, and commercialize a product. Often a bioentrepreneur starts with identifying a need and then creates a specialized niche market to satisfy that need. To be successful, the entrepreneur must become skilled at bringing together the science, research and funding to make it happen. Of course, it doesn't hurt to have the business know-how and convincing bravado to pull it off successfully.

In 1998 Ron Cohen, founder of Acorda Therapeutics, Inc., wrote with the confident voice of a presumedly successful bioentrepreneur. The following are excerpts from Alternative Careers in Science: Leaving the Ivory Tower edited by Cynthia Robbins-Roth (Academic Press, 1998; 2nd edition, Academic Press, 2005). Dr. Cohen contributed Chapter 9 - "Entrepreneur and Company Founder: Starting Your Own Company and Surviving".

During my internal medicine residency at the University of Virginia, I saw my first patient with SCI. That experience stayed with me even after I went back to New York City and practiced medicine while pursuing the other love of my life – the theater. For a while, I lived a dual life as medical director of a clinic in the Wall Street area and as an ER physician, while also taking acting classes, auditioning and working in commercials, starring in off-off Broadway plays, and appearing as a contestant on Jeopardy. I was having a wonderful time, living with one foot in each of two very different worlds.

But then in May 1986, friends from my medical school class at Columbia called and told me about a scientist friend of theirs, Dr. Gail Naughton, who was starting a company that would focus on her work in tissue proliferation. She needed a scientist with an M.D. who was good at making presentations to help build the company. An “acting” M.D. seemed like the perfect solution. My friends had shown Dr. Naughton tapes of me being interviewed for the local news and as a contestant on Jeopardy, and she decided that she had found what she was looking for.

I had never considered going into the business world – but this made no difference to Gail. At my first meeting with her, her husband, and her two kids, she pulled out a piece of paper with three lines of writing that essentially said, “I, Ron Cohen, will work for Marrow-Tech for $X,” and she said, “Sign here!” While I wanted to think about it, Gail said, “You don’t understand. I want you to sign here!” So I did, and that is how I got into biotech – it was an impulse based on the way Gail and I clicked; it just seemed to be the right thing to do.

Brief Bio of Ron Cohen, M.D., President, CEO, and Founder of Acorda Therapeutics., Inc.:

Dr. Cohen previously was a principal in the startup team of Advanced Tissue Sciences (ATS), a public biotechnology company in La Jolla, California engaged in growing human tissues in the laboratory — including skin, cartilage, liver and bone marrow — for use in transplantation. Dr. Cohen served as Vice President, Officer and Director of the Company from 1986 through 1992. He established and headed the Company's clinical, regulatory, quality assurance, and investor & public relations departments, also sharing responsibilities for business development, patent prosecution, public stock offerings and preclinical research and development. Dr. Cohen received his B.A. degree in Psychology from Princeton University, and his M.D. from the Columbia College of Physicians & Surgeons. He completed a residency in Internal Medicine at the University of Virginia Medical Center, and is Board Certified in Internal Medicine. Dr. Cohen also serves as a member of the Health Sciences Advisory Council at Columbia.

According to the record found at American Board of Internal Medicine (ABIM), Dr. Cohen was certified in Internal Medicine on September 12, 1984 and that certification will be valid indefinitely. "Certificates awarded in Internal Medicine prior to 1990 do not require renewal. However, ABIM encourages all diplomates voluntarily to renew certificates relevant to their practice." That can be rather useful to maintain that doctorly persona.

I founded Acorda from scratch and on my own dime. This meant several years of deciding which area I wanted the company to pursue; plowing through the technical literature and attending scientific and clinical conferences to find out the current status of SCI research and therapeutic development; identifying the top scientists in the field and persuading them to work with me; figuring out what the other biopharmaceutical companies were doing in the area; and getting the various not-for-profit foundations that fund SCI research to cooperate with us rather than compete. Then I had to write a business plan that made scientific, clinical, commercial, and financial sense. Hardest of all, I had to round up sufficient investment dollars to fund the company. This last task never ends, but you won’t have a company without the first infusion of dollars.

[...] At some point, however, experience is crucial. My Acorda experience is very challenging – huge amounts of work and stress, but at least I knew what was coming. I strongly urge budding entrepreneurs to ally themselves with people who do have that experience, to balance out their ignorance. Scientists need to align themselves with people with management and people skills, those who have been through it before. This requires swallowing your ego. It is hard to share control with others, but often it is a fatal mistake for entrepreneurs to try and go at it alone. Strong scientific skills do not translate directly into excellence in other areas. A Nobel laureate does not necessarily make a good CEO.

When examining the history of Fampridine-SR (4-aminopyridine in a patented sustained-release formulation) in use to treat spinal cord injury, it becomes apparent that Dr. Andrew Blight was key in the preclinical research. So it is no surprise that Dr. Cohen convinced him to join the team. In fact, it was Dr. Blight who was left to represent Acorda in front of a disgruntled FDA panel in 2000 after Dr. Cohen had given bold ultimatums to the same panel in 1999. The topic of the discussion centered around the develop of 4-aminopyridine in the treatment of multiple sclerosis and patient access to compounded formulations.

Until April 2004 when Acorda announced disappointing results from two Phase III trials of Fampridine-SR in the treatment of incomplete SCI, Acorda had committed more of its resources to studying spinal cord injury. It was then that Acorda turned to focus primarily on multiple sclerosis which had been on the backburner. It's even apparent in reading the early filing materials for the unsuccessful 2003 S-1 Initial Public Offering launch that MS was almost an afterthought.

More from Alternative Careers in Science, 2nd edition (2005) -

In 2003 to 2004, Acorda weathered two significant setbacks, one a decision by some of its investors not to accept a $45 million initial public offering and the other a disappointing result in two pivotal trials of its lead drug candidate for SCI. We promptly set out to acquire a commercial product for our therapeutic area and succeeded in bringing in Zanaflex, an approved drug for spasticity due to SCI, multiple sclerosis (MS), stroke, and other central nervous system injuries. We are now generating revenue from this drug, and we have built our initial sales and marketing organization. In 2005, Acorda has 59 employees and, in addition to Zanaflex, a drug product that is about to enter Phase 3 of a pivotal trial for restoration of function in MS. We have additional, exciting pipeline products that have been shown to repair nerve pathways in the spinal cord and brain of animal models. The company has raised more than $140 million since inception, mostly from venture capital groups. Biotechnology companies underscore (perhaps more than most) the need to have management teams that are creative and opportunistic at every turn, allowing the companies to come through the inevitable setbacks successfully.

Acorda Therapeutics, Inc., was successful in launching its IPO in 2006 shortly after which Ron Cohen rang the bell on Wall Street, on April 7,2006 to be exact. So if Acorda does become a profitable pharmaceutical company, it will be due to the needs and hopeful spirit of multiple sclerosis patients worldwide. We are often looking for ways to improve our symptoms. Just look at the results of the recent survey commissioned by Acorda and the National MS Society which discussed the effect of Mobility on the Quality of Life of MS Patients. I know that some fellow bloggers were just thrilled to read that press release and even more elated to know that Acorda thinks they have the product to help. Yet to be FDA approved and anticipated to cost $5000-10,000 each year.

Finally, to those of you who may be unconvinced that a former actor-physician could become a multi-millionaire before his fledgling drug company launches its lead product, think again. In 1998, the board of directors may have voted to pay Ron Cohen a salary of $120,000. But in the years since, his salary and bonuses have increased substantially, not to mention the stock he has cashed in during the past two years and the substantial stock awards and options he continues to receive.

• 2003 Salary $290,000 Bonus $ 60,000 = $350,000
• 2004 Salary $305,000 Bonus $120,000 = $425,000
• 2005 Salary $305,000 Bonus $145,000 = $450,000
• 2006 Salary $370,000 Bonus $225,000 = $595,000
• 2007 Salary $440,000 Bonus $190,000 = $630,000
• 2008 Salary $460,000 Bonus TBD
• Stock Profits realized since Oct 2006 - more than $6,000,000
  

For tips on financing, read Ron Cohen's article from one year ago, "Six Steps to Successful Financing," published online by Bioentrepreneur.

Happy Birthday!!

Hi Sweetie - Happy Birthday!!

For 75 days we are the same age.

Our kittens are 14 weeks old today as well.

Pippin and Musette

Wo ist Beethoven?

[Begin reading with Eyes in the Back of My Head]

Early in the summer of 2002, I received a phone call from the orchestra manager for the AIMS festival in Graz, Austria. AIMS stands for American Institute of Musical Studies which is a 6-week intensive program for opera singers and pianists. The orchestra members range from seasoned professionals to college students, some choosing to return year after year. One of the returning horn players that year unexpectedly could not attend due to having won a spot with the U.S. Navy Band in Washington, D.C.

Besides playing lots of great music, we had a little time to travel on free days/weekends. A fabulous advantage the European countries have for easy travel is found in their extensive train system. Some of the popular destinations for the orchestra musicians were Vienna, Salzburg, Budapest, Prague, and Venice. A couple of guys even hopped on a plane and flew to Dublin for the weekend once, thanks to Ryanair.

My first trip out of town was to Vienna, Austria. Home of the former Hapsburg Monarchy in addition to generations of famous musicians. Haydn, Mozart, Beethoven, Czerny, Schubert, Johann Strauss I & II, Brahms, Bruckner, Mahler, Schoenberg, Berg, Webern, Ligeti, and others.

While in Vienna, two other girls from the orchestra and I wanted to visit Zentralfriedhof, the second largest cemetery in Europe, where a number of these famous composers are buried. Using high school Deutschgesprachen skills, I searched for Beethoven's gravesite.

Können Sie mir helfen? Weißen Sie wo Beethoven ist? Danke.

After encountering some women who were tending to the gardens throughout the cemetery, we finally found the Musiker. If we had only walked straight down the central lane towards Karl Lueger Kirche, we would have found the Musician's Corner on the left.

On another long weekend, we traveled to Prague where a bit more walking was required. This particular weekend it became apparent that I had become a nuisance for my travel companions. It seemed that at every opportunity I needed to rest on a bench.

Whew!!

Even the pregnant percussionist who was 5-months along had more energy than I did. Sometimes it took a great amount of effort just to keep up. My calves were knotted and my legs felt slow and heavy. I chaulked it up to being a little out of shape and having developed stiff, swollen ankles.

Although walking became difficult, I was very glad to have taken part of a tour of the Jewish Museum in Prague.

"Founded in 1906, the original intent of the Jewish Museum was to preserve artifacts from the synagogues of Prague that were being liquidated at the turn of the century due to reconstruction of the Jewish town. The museum was closed to the public after Nazi occupation in 1939. The Nazis decided not to destroy the Museum, but instead use it as a "Museum of an Extinct Race"; the Germans hired Dr. Stein, historian and founder of the Museum, to catalogue tens of thousands of confiscated items from more than 153 destroyed Jewish communities throughout Bohemia and Moravia."

We left Prague on August 11th just a day and a half before low-lying areas of the city were evacuated in anticipation of tremendous flooding. We were fortunate to have left a day early due to the rain as this was determined to be the worst flood to hit the capital city in 200 years.

After returning to the States and during a routine doctor's appointment (gyn), I mentioned the experience I had with swollen, stiff (and painful) ankles and the heaviness of my legs during my travels. She flippantly stated that the swelling was due to lack of muscle tone which was due to being out of shape.

What I didn't know at the time is that the lymph system relies upon muscle relaxation/contraction to help move lymphatic fluid out of our limbs and toward the heart. But if your muscles fail to relax sufficiently, then fluid gets trapped in your extremities. Too bad I didn't know enough to perform the appropriate yoga poses to maximize lymph drainage and induce muscle relaxation. I've learned a lot since then.

Next: Watch It, Smartie Pants

“sharing what I love with other people sometimes is more satisfying than playing” - Alana Vegter

This morning I read the following NYT article which strummed some familiar heart strings. The life of a musician comes in many forms.

And the Band Honked On
By DANIEL J. WAKIN
Published: June 22, 2008

THE classroom filled with the sounds of a band struggling to be born, a cacophony of squealing and buzzing. Middle school students in a working-class Brooklyn neighborhood were trying to produce the note F.

It was early in the school year. A young professional French horn player named Alana Vegter, a thoroughbred musician trained by elite teachers, took a handful of trumpet and trombone players into an equipment supply room. Speaking in the flat tones of the Chicago suburb where she grew up, Ms. Vegter tried to coax notes out of each player. A tall sixth-grade trumpeter named Kenny Ocean, his pants sagging around his hips, played too high, then too low. A smile spread across his face when he hit it right.

“You see, every time you do it, it gets easier,” Ms. Vegter said. On her cue they all bleated together. “I’m starting to hear everybody making nice, healthy sounds,” she said, half in praise, half in hope.

So began Ms. Vegter’s year in Ditmas Junior High School, Intermediate School 62, in the Kensington section of Brooklyn. It was a year that would teach her the satisfaction of tiny victories in a place where homelessness means that some kids cannot take their instruments home to practice, where chronic asthma forces some to switch from wind instruments to percussion, where the roar of a lunchroom leaves a newcomer stunned.

Ms. Vegter, 25, was there as part of a well-financed experiment by some of the nation’s most powerful musical institutions. The experiment is called, clumsily, the Academy — a Program of Carnegie Hall, the Juilliard School and the Weill Music Institute (the institute being an arm of Carnegie).

In its second season, which ended this month, the academy extended fellowships to 34 graduates of leading music schools to receive high-level coaching and lessons in a two-year program. They play concerts on Carnegie’s stages and participate in master classes. Part of the deal is a commitment to teach one and a half days a week at a New York public school, which pays the academy $13,200 for the service.

The idea is ambitious: Mold a new kind of musician in a time of declining audiences and — seemingly — dwindling relevance for classical music. Performers focused intently on artistic development are being asked to step outside themselves and spend time away from their instruments.

“We are working to equip musicians who will continue to grow,” said Clive Gillinson, the executive and artistic director of Carnegie Hall. “We’re looking at the life of the musician of the future, what it could be and what it will be. If we can enable musicians to become utterly fulfilled, they will end up contributing far more to society and to music.”

It is a noble goal, and maybe a tall order, given the glut of musicians who continue to pour out of music schools to face a life that has always been tough psychically and economically — whether for a Mozart groveling before royalty or a modern-day conservatory grad struggling through orchestra auditions in the provinces.

The academy is also intended to give a concrete boost to music education, which is held to be in serious decline: both a cause and an effect of the diminishing stature of classical music.

The program had its growing pains. One fellow was asked to leave for blowing off his teaching commitment. Others scoffed at the mushiness of teacher-training sessions. And a year spent following Ms. Vegter at Ditmas showed how high-minded concepts can run smack into reality.

At the same time the year demonstrated how one talented musician could be made wiser as a player and person, and how a little personal attention from an emissary of high culture could improve the lives of children.

MS. VEGTER, WITH HER AUBURN HAIR pulled back in a ponytail, has the carriage of a jock and the looks of a prom queen, which she once was. But her jock world was band, and her town of 13,000 people, Lemont, Ill., is band country. It is a community where music education works.

The majority of middle schoolers are in band. Competitions begin in the sixth grade. Band boosters pay for travel, instruments and uniforms. Band alumni come back for homecoming. The Lemont High School band won the state championship in its division from 1998 to 2005, including three of Ms. Vegter’s years there. Four of her classmates are professional musicians. “People respected it,” she said.

She was held in awe by fellow students in high school. “She was probably one of our top one or two or three all-time that we’ve had,” said David Nommensen, her band director.

Ms. Vegter’s father owns a carpet-cleaning company. Her mother died when she was 16. Inspired by a French horn-playing baby sitter, she began the instrument at 10 and showed immediate talent.

At DePaul University in Chicago she studied with Jon Boen, the principal of the Lyric Opera of Chicago. She played in the school band and orchestra and in the respected Civic Orchestra of Chicago, a training ground of the Chicago Symphony Orchestra. She went off to Juilliard for her master’s degree, one of two horn players admitted as graduate students that year, and studied with the exacting Julie Landsman, a co-principal of the Metropolitan Opera Orchestra.

On the cusp of a career Ms. Vegter displays the idealism of the young. “I am a musician simply because music is what makes me most happy in life,” she wrote this spring in an e-mail message distilling her feelings. “Nothing else measures up. Not a steady paycheck, not social status.”

Her instrument is fickle. Yet “when everything lines up and playing the horn feels easy,” she said, “I feel so incredibly alive.”

Ms. Vegter is realistic about her prospects. She wants to play in a major orchestra but knows how hard it is to win a spot. Yet she remains sunny. “People who work hard and mean well tend to have things work out,” she said. Whatever happens, music will remain a large part of her life, she said.

Read the rest of And the Band Honked On.

The Purple Jumper

[Begin reading with Eyes in the Back of My Head]

After the episode of optic neuritis in 2000, I kept my fingers crossed regarding health issues. The neuro-opthamologist explained that the current theory was that I would be at increased risk of developing multiple sclerosis within five years following a Clinically Isolated Syndrome (ICS), after which time my risk would return to that of the general public.

In the years that followed, I learned that my Primary Care Physician (PCP) was rather conservative in treatment plans. So I carefully decided when it was necessary to seek treatment. In 2002, I finally made an appointment to discuss the insomnia I had been experiencing for about three months. My sleep patterns had deteriorated to the point that I hadn't gotten more than four hours of shut-eye, the kind that actually takes you deep into REM sleep, in several weeks. When I became so weak that taking the stairs caused enormous shaking, I finally admitted that I needed medical intervention, ie help.

In addition to discussing the insomnia, I asked for a referral to a dermatologist to have some warts frozen off my left hand. My home treatments were serving to be rarely ineffectual. Instead, the doc had recently acquired a new toy, a wart-freezing device, which worked a little like a spray can. "We can do that here." Ok, sure.

First went the large wart over the big knuckle of my index finger. No reaction from me. Then the wart near the nailbed on the middle finger, followed by the one on my pinkie. A little ouchie there. Back to the big one. "That doesn't hurt?" Not really. More freezing to get it really good. The skin looks angry now. Hopefully that does the job. The doc leaves the room and I'm sitting in the chair next to the computer. Oh boy, it's starting to get a little hot in here. Sweaty. The room is beginning to look darker, gray.....sweating....dark gray....

At some point later the nurse comes back into the room. "ms. emrich, ms. emrich." Huh? "ms. emrich." Whaat? smelling salts, blood pressure cuff. I was still perfectly balanced with only my head bent over my lap and hands placed on the arms of the chair. I had passed-out cold. "here, drink this" 7-Up. Apparently the pain finally DID register causing a dramatic drop in blood pressure which caused me to faint. Classic vasovagal syncope reaction.

The doctor insisted that I sit a while to make sure I was okay to drive. She also stated, "let's get you some sleep." That was the first time I was prescribed Ambien as a sleep aid (which came in rather handy when I spent two months performing in Austria later that summer). I almost thought that I would be sent home to try less aggressive, behavior-modification therapy first. But I guess passing out unexpectedly has it's perks.

Sure fainting in the doctor's office was a little embarrasing. But not as embarrasing as what I discovered that night as I was preparing to go to bed. I reached to place something in the pocket of my purple jumper to take it upstairs. Where's my pocket? What?! My front-facing pockets were hiding on the back-facing portion of my body.

I had managed to get dressed that morning with my clothes on backwards. Nobody had said a single word about it all day long. Not the nurse who made me stand on the scale. Not my students who probably just wondered. Not even my Mom with whom I had eaten supper. I had been out in public wearing my purple jumper with the pockets in the back and the tag in the front.

What a rare sight that must have been. But at least, I would finally get a full nights sleep for the first time in months. I don't think I've ever made that particular clothing mishap again. I think.

Next: Wo ist Beethoven?

Carnival of MS Bloggers #13

Welcome to the Carnival of MS Bloggers, a bi-weekly compendium of thoughts and experiences shared by those living with multiple sclerosis.

“If a person who indulges in gluttony is a glutton, and a person who commits a felony is a felon, then God is an iron.”- Spider Robinson

God is THE Master of Irony 

by Shauna

Many many years ago, a friend (George) at university introduced me to the writings of Spider Robinson. The man is very funny and insightful and punny. Makes for a very good combination. So I enjoyed everything he wrote. Then I read Mindkiller. The second chapter of Mindkiller had actually been included in an anthology of short stories. The story was called God is an Iron.

When I first saw this title I thought "iron:anvil". Then I thought "iron:something to remove wrinkles". But God is an anvil or God removes wrinkles didn't make a lot of sense to me. So I decided to read the story to find out what it meant. And boy, was Spider right. God is THE master of irony.

All this is to simply set up how I found out I had MS.
In January, 1998, my (ex)husband and I went on vacation to Quebec City. During the height of the big ice storm, no less. I wanted to go to St. Ann de Beaupre to send my grandmother a postcard from there. If you are Catholic you probably know about the place. It is a shrine to Saint Anne, the mother of Mary, grandmother of Jesus. People have been going there on pilgrimages for ages to seek relief from physical ailments and afflictions. My grandmother had been there in 1939 (she had polio as a child that left her lame). I knew she'd appreciate that we had made a stop there.

The church that is there is really a gorgeous piece of work. We went into the church and were the only ones. We walked around, admiring the structure, the tiles, and amazed at the number of crutches, canes, and orthotics that were tacked to the front pillars, left behind by people who had been "miraculously" cured.

The next day, as I was brushing my hair, my right arm felt kind of weak. And I was tripping over my right foot.; I was having trouble holding my toothbrush and even writing. We returned to Halifax and I went back to work, but went to see my family doc about the increasing weakness. She told me to come back if it got any worse and she would try to get me in to see someone. Two days later I was back in her office and she was on the phone to a colleague who saw me at the hospital that afternoon. At 5:45 that evening the neurologist was telling me I had MS. A couple of hours later, I was telling my parents that it was a little ironic that my symptoms began the day after I had visited St. Anne de Beaupre. And that's when it hit me.: God really IS an iron.

My grandmother received the postcard and just loved it. But the entire family was sworn to keep from her my diagnosis. She passed away a year and a half later and I like to think she passed into heaven dancing a Sottish jig and then, upon discovering I had MS, giving God a piece of her mind about that. My grandmother had a wonderful sense of humour, but I doubt she would have appreciated the irony.
"I went to St. Anne de Beaupre and got afflicted." - Shauna

Sometimes the MS journey is smooth, other times bumpy. Sometimes it is scary. Sometimes it is frustrating. Sometimes it is humbling. Many times observations of how an individual handles the bumps along the way, mentally and physically, can become inspirations for others. What follows comes from one such moment.

While having a moment...., Linda of BRAIN CHEESE penned the following poem. I thank her for giving me permission to shed a few tears of my own.

Barbie & The Milk Proverb
Let me cry
Over my spilled milk.
It is not the milk
I grieve,
But loss of
The simple act of
Pouring
Liquid into cup.
How I take for granted
What used to be
Mindless tasks
Of rote memory.
My flesh no longer
Feeling the smoothness
Of the cup
Beneath fingers
Weakened by disease.
These foreign appendages,
Stiffly positioned
Like arms
Hanging from a
Plastic doll,
Serving no purpose.
Barbie has no brain
To bring these
Hands
Back to life.

At BARBARA'S TCHATZKAHS, one can find important topics and articles highlighted by Barbara who often adds a personal touch. Here is one of those posts in which she asks the question - "Why Doesn't My Doctor Know This?" and finds a possible answer an article by Dr. Holtorf which she republishes on her blog. Go there to read the answers.

I found this out 12 years ago when trying to get a diagnosis other than "its all in your head" for the reason I was: paralyzed at the time on the left side, unable to eat, in excruciating pain that defied words, unable to walk more than 2 feet without falling over, and running a fever that would not go away.
When a doctor who knew what she was talking about looked at the already done CAT scan and blood work? My diagnosis jumped out at her. She was appalled that it was missed but not surprised.

Other doctors? Dismissed it as nothing simply because they didn't understand it or were uninformed.Because they were uninformed? stupid? unwilling to deal with a chronically ill patient? pressured by the insurance companies to get rid of chronically ill patients? or all of the prior?

Top Ten Things to Do Right After Being Diagnosed with Multiple Sclerosis 

by Diane J Standiford

The following suggestions are from a person (me - Diane) diagnosed with MS in 1990. They got me through the first days and continue to help me thrive while under the influence of this chronic, progressive disease with no cure. The rare cases of MS will be benign or rapidly progress downward; but the chances of YOU having either of those cases is as likely as winning the lottery. The following suggestions are for all the rest of us. Together we will make it through and just maybe find beauty where we never dreamed it might be.

• Do not PANIC. Life is full of bumps. This will just be another one and you will land safely on the other side.
• Rejoice. You do not have a brain tumor. MS will not kill you.
• Grab some MS brochures on your way out of the neurologist’s office.
• Call your friends, and loved ones and explain what you found out. They will follow your lead from here on out.
• Start learning about multiple sclerosis. Learn to spell it. If you have a computer, begin looking for MS information sites like the National MS Association and your local MS Society. Search MS Blogs for personal stories from people just like you.
• Reach out to people for help dealing with this new part of your life. There are social workers, occupational and physical therapists, naturopaths, all waiting for your call.
• Talk to you. What is your biggest concern? Make a list. Prioritize and begin to take action. There is no concern that others with MS haven’t had, and know that all can be handled without the world stopping from spinning.
• Write in large print on a large poster board: “I will be flexible.” (This will be necessary both physically and mentally) and “I can be certain that nothing is certain.” That is especially important for type-A personality types. You can still feel certain (of uncertainty) and you can stay in control. (Of your knowledge that you no longer have control of your body.)
• Prepare. Prepare yourself by accepting all your new physical, emotional, and mental changes---women, recall when you got your first period; men, recall when your facial hair first needed shaving---you got used to the new you. You accepted the changes because they were not going way anytime soon. Prepare your family, friends, and co-workers; educate them. I know this is controversial; but sooner or later you will need their help. This leads to…
• Become an opportunity for others to become more loving and giving.

Thank you Diane for such great advice. And while navigating the bumps, I hope that you are also out there living life. On a recent Saturday I enjoyed living despite my fulltime companion, Multiple Sclerosis.

To combat fatigue, I used my handicapped placard and took a long nap between events. My Sweetie and I arrived at the second event of the day more than an hour after it had begun, but that was fine. Sure I got so fatigued in the evening that I could hardly stand steadily, but that was not a problem (although I was winning that 2nd game of pool after having won the first one too - darn MS). We left the party early, but so did those who followed right behind us.

Flag Day, Graduation, Ethiopia 

- A Day in the Life of Lisa Emrich

The “Stars and Stripes”, the official National symbol of the United States of America was authorized by congress on that Saturday of June 14, 1777 in the fifth item of the days agenda. The entry in the journal of the Continental Congress 1774-1789 Vol. Vlll 1777 reads “Resolved that the flag of the thirteen United States be Thirteen stripes alternate red and white: that the union be thirteen stars, white in a blue field, representing a new constellation.”

[from The National Flag Day Foundation]

This morning I attended the graduation ceremonies for one of my high school horn students. She had received an award and each year the recipient of that award is invited to perform at graduation. So a brave hornplayer, Leslie, followed the valedictorian's speech and the commencement speaker by performing Eugene Bozza's Chant Lointain for Horn and Piano. I played the piano part. She rocked!!

One interesting thing that I noted occurred near the beginning of the proceedings as the choir sang the National Anthem. All heads were directed at the humongous flag hung on the gymnasium wall, but maybe only a third of the attendees had hand over heart. Not even all of the faculty members made this small gesture. Perhaps observing whether someone places his right hand across his chest has become less a symbol of patriotism and more one of cultural indoctrination. I think that it has less to do with respect than it does outward signs of conformity.

A second interesting tidbit came during the invocation. First an official school invocation was read; it was also printed in the program. Then three students read verses from three texts. One young man chose a verse from Joshua in the Old Testament of the Bible. The verse chosen by a second young man was recited in the original Sanskrit before he provided the translation. Then a young woman recited a Hebrew verse and it's translation. An inclusive collection of faiths and beliefs represented.


Then the kicker. As the Head Master, this is a private school, was sharing bits about the graduating class he mentioned all of the college applications, all of the acceptances, all of the honors and scholarships. But the one he saved for last was the announcement of a senior who had been presented her commission to attend the United States Military Academy at West Point.

That honorable graduate is none other than my horn student, Leslie. Way to go girl!!

In the afternoon, my Sweetie and I attended a graduation party for the son of one of his co-workers. What a party that was! Wonderful bounty of Ethiopian cuisine, including a traditional honey 'beer' made fresh by the host. Did I mention food? Lots and lots of food.

Later in the evening - I believe many guests were staying the night - we shot some pool and enjoyed music of which neither of us understood a word. The father of the graduate played some music videos in the background which showed copious examples of traditional Ethiopian-style dance. Well, can you see where this is leading?

A drink (coke) was taken out of my hand while I sat in a cozy armchair and I was recruited to join the dancing. OK. I don't dance. Never have really. But many, many, many eyes were on us in that grand basement. So I did my best at replicating the shoulder-shrug/shake and arms bowed just so of a native Ethiopian woman. Out came the video cameras I'm embarrassed to say and much laughter bounced around the room. I even grabbed my Sweetie to share in the embarrassment. I'm afraid their friends and family will be talking about the party during which the only non-Africans joined the dance.

Now tell me honestly. Does it matter that in one day I celebrated American patriotism, Christian scripture, original Hindi Sanskrit, Hebrew Torah, and the fellowship of a mix of Muslims and Christians? Such is life near the Nation's Capital.
T

oto. We are definitely not in Kansas, I mean Oklahoma, any more.

This concludes the 13th edition of the Carnival.
The next Carnival of MS Bloggers will be hosted here on July 3, 2008. Please remember to submit a post (via email) from your blog of which you are particularly proud, or which you simply want to share, by noon on Tuesday, July 1, 2008.

Thank you.
Comments for this post.

Secret Worlds

Thank you for sharing your worlds with me.

4-AP, Fampridine-SR, and Multiple Sclerosis

If you are just joining the conversation, first read What is 4-Aminopyridine? and 4-AP, Fampridine-SR, and Spinal Cord Injury.

In 1990, Elan Corporation, plc licensed from Rush-Presbyterian Hospital in Chicago the Know-How related to fampridine (4-aminopyridine) for symptomatic treatment of multiple sclerosis. By 1997, Elan Corporation, plc had obtained three U.S. patents related to the sustained-released technology for Fampridine-SR (slow-release fampridine/4-aminopyridine).

Clinical Research at University of Maryland, Baltimore (1990-97):

Bever, Leslie, Panitch, et al. Studies sponsored by Elan.

• Ann Neurol, April 1990 - Preliminary trial of 3,4-diaminopyridine in patients with multiple sclerosis. 10 patients. Bever Jr, Leslie, Camenga, Panitch, Johnson. University of Maryland School of Medicine, Baltimore.
• Ann Neurol, 1994 - The current status of studies of aminopyridines in patients with multiple sclerosis. Bever Jr. University of Maryland School of Medicine, Baltimore.
• Neurology, Jun 1994 - The effects of 4-aminopyridine in multiple sclerosis patients: results of a randomized, placebo-controlled, double-blind, concentration-controlled, crossover trial. 8 patients. Bever Jr, Young, Anderson, Krumholz, Conway, Leslie, Eddington, Plaisance, Panitch, Dhib-Jalbut, et al. University of Maryland Hospital, Baltimore.
• Neurology, Dec 1996 - Treatment with oral 3,4 diaminopyridine improves leg strength in multiple sclerosis patients: results of a randomized, double-blind, placebo-controlled, crossover trial. 36 patients. Bever Jr, Anderson, Leslie, Panitch, Dhib-Jalbut, Khan, Milo, Hebel, Conway, Katz, Johnson. University of Maryland School of Medicine, Baltimore.

First Clinical Trials of Fampridine-SR in MS (1997):

Schwid, Goodman, Bever, et al. Studies sponsored by Elan.

• Neurology, Apr 1997 - Quantitative assessment of sustained-release 4-aminopyridine (EL-970) for symptomatic treatment of multiple sclerosis. 10 patients. Schwid, Petrie, McDermott, Tierney, Mason, Goodman. University of Rochester Medical Center, Rochester, New York.
• Long-term study abruptly termindated, thus incomplete and unpublished - Bever Jr, et al. University of Maryland School of Medicine, Baltimore, Maryland.

In April 1998, Acorda Therapeutics, Inc. and Elan EIS entered a joint venture and formed the MS Research & Development Corp (MSRD). MSRD turned around and licensed research and development technology from Elan to develop Elan's proprietary oral sustained release formulation of fampridine for the treatment of multiple sclerosis. MSRD was permanently terminated in September 2003. [*see explanation below]

Regarding Compounding Pharmacies and Bulk Drug Lists

Prior to the Food and Drug Administration Modernization Act of 1997, 4-aminopyridine was available from compounding pharmacies in the U.S. This new legislation specified that "a drug product may be compounded under subsection (a) if the licensed pharmacist or licensed physician-- '(A) compounds the drug product using bulk drug substances,..."

A letter dated June 4, 1998 submitted by a board member of the South Carolina Board of Pharmacy nominated 21 bulk drug substances as candidates for the bulk drug list, including 4-aminopyridine. The package submitted includes a review of safety and efficacy data, including peer reviewed medical literatureune of 4-AP (see pages 1-61).

During a May 1999 FDA meeting (read transcript beginning p.40) discussing candidates for the national bulk drug list, Dr. Bever was questioned extensively regarding the long-term trial he was conducting for Elan which was abruptly terminated. A panelist for the FDA asked a representative of Elan, "compounded products have significant risk for adverse effects, but, yet, your company took a group of patients who was on your product and hung them out to dry. Why did that happen?" (see page 72)

Later during the meeting, Dr. Cohen summed up his objection to including Aminopyridine on the Bulk Drug List.

"If pharmacy compounded fampridine continues to be made available, we would not be able to justify the significant additional investment of time and resources that an expanded access study would require. Moreover, we would have to seriously review whether it would be economically feasible for us to continue clinical development of this compound. We believe that such an outcome would poorly serve the long-term interest of the patients and their healthcare providers, who deserve to have a therapy that can be prescribed with assurance of reliable dosing, appropriate indications for use and overall safety and efficacy. Such assurance can only be obtained for this drug if it is developed under INDs and approved by FDA under an NDA." - Dr. Cohen

During a June 13, 2000 FDA meeting (read transcript beginning p.20) discussing updates to the Acorda's promised Expanded Access Study of Fampridine which never happened. A question from the panel was "Are you more interested in patients with MS or spinal cord injuries?"

"Well, as a company, we were founded primarily to develop therapies for spinal cord injury, but because of our interest in demyelination in spinal cord injury, we have broadened that to include MS. So, we are now equally interested in both conditions, although our roots are in the spinal cord injury side of this." - Dr. Blight (p.28)

Phase II Clinical Trials (2000-04):

In December 2000, Accorda announced they would Initiate Phase II Trial of Fampridine-SR in MS (MS-F201). Results of that trial were presented at the Sept 2002 ECTRIMS meeting but weren't published until 2007.

• Mult Scler, April 2007 - Fampridine-SR in multiple sclerosis: a randomized, double-blind, placebo-controlled, dose-ranging study. 36 patients. Goodman, Cohen, Cross, Vollmer, Rizzo, Cohen, Marinucci, Blight. University of Rochester Medical School, Rochester, New York. (MS-F201)
• Nat. SPI Assoc, April 14, 2004 - Acorda Therapeutics Reports Results of Fampridine-SR Clinical Trials. 200 patients. Goodman, et al. University of Rochester Medical School, Rochester, New York. (MS-F202)

Phase III Clinical Trials (2005-08):

May 30, 2005 - Announce Special Protocol Assessment (SPA) for Phase III
Sep 26, 2006 - Announce Positive Phase III Results in MS ; results presented at AAN meeting on May 2, 2007 (MS-F203)

Jan 28, 2008 - Announce Successful QT Safety Study
Mar 25, 2008 - Announce Survey Results Mobility Quality of Life
Jun 2, 2008 - Announce Positive 2nd Phase III Results in MS (MS-F204)

Studies designed to develop and improve quantitative functional measures for use in determining disease progression or symptomatic improvement (1997-2002): Schwid, Goodman, et al. Rochester.

• Neurology, Nov 1997 - The measurement of ambulatory impairment in multiple sclerosis. Schwid, Goodman, Mattson, Mihai, Donohoe, Petrie, Scheid, Dudman, McDermott. University of Rochester Medical Center, Rochester, New York.
• Neurology, Sep 1999 - Quantitative assessment of motor fatigue and strength in MS. Schwid, Thornton, Pandya, Manzur, Sanjak, Petrie, McDermott, Goodman. University of Rochester Medical Center, Rochester, New York.
• Neurology, Dec 2000 - Are quantitative functional measures more sensitive to worsening MS than traditional measures? Schwid, Goodman, Apatoff, Coyle, Jacobs, Krupp, Miller, Wende, Brownscheidle. University of Rochester Medical Center, Rochester, New York.
• Arch Neurol, Jun 2001 - Use of the multiple sclerosis functional composite as an outcome measure in a phase 3 clinical trial. Cohen, Cutter, Fischer, Goodman, Heidenreich, Jak, Kniker, Kooijmans, Lull, Sandrock, Simon, Simonian, Whitaker. The Mellen Center, The Cleveland Clinic Foundation, Cleveland, Ohio.
• Neurology, April 2002 - Quantitative functional measures in MS: what is a reliable change? 20% change can be considered a reliable threshold to indicate true change in function for an individual. Schwid, Goodman, McDermott, Bever, Cook. University of Rochester Medical Center, Rochester, New York. Sponsored by NMSS. Presented at Sept 2002 ECTRIMS meeting.

Review of Potassium Channel Blockers in MS (2002-07):
Hayes, Judge, Bever Jr, et al.

• Curr Opin Investig Drugs, Nov 2000 - Fampridine Acorda Therapeutics. Darlington. University of Otago, Dunedin, New Zealand.
• Mol Pharmacol, April 2002 - Determinants of 4-aminopyridine sensitivity in a human brain kv1.4 k(+) channel: phenylalanine substitutions in leucine heptad repeat region stabilize channel closed state. Judge, Yeh, Goolsby, Monteiro, Bever Jr. VA Maryland Health Care System, Baltimore.
• CNS Drug Rev, Winter 2004 - The use of 4-aminopyridine (fampridine) in demyelinating disorders. Hayes. University of Western Ontario, London, Ontario, Canada.
• Pharmacol Ther, July 2006 - Potassium channel blockers in multiple sclerosis: neuronal Kv channels and effects of symptomatic treatment. Review to Date. Judge, Bever JR. VA Maryland Health Care System, Baltimore.
• J Rehabil Res Dev, Jan-Feb 2006 - Voltage-gated potassium channels in multiple sclerosis: Overview and new implications for treatment of central nervous system inflammation and degeneration. Judge, Lee, Bever Jr, Hoffman. VA Maryland Health Care System, Baltimore.
• Expert Rev Neurother, May 2007 - Fampridine-SR for multiple sclerosis and spinal cord injury. Hayes. University of Western Ontario, London, Ontario, Canada.
• Recent Patents in CNS Drug Discov, Nov 2007 - Potassium channel blockers and openers as CNS neurologic therapeutic agents. Judge, Smith, Stewart, Bever Jr. University of Maryland School of Medicine, Baltimore.

*In April 1998, the Company [Acorda] issued to Elan 2,300,000 shares of Series F, at a per share price of approximately $5.22, for aggregate proceeds of approximately $12 million. Also, in April 1998, the Company entered into a joint venture agreement with Elan. The $12 million proceeds from the sale of the Series F was then transferred to MS Research and Development Corp. (MSRD), a joint venture company of which the Company owned approximately 80% and Elan owned 20%, approximately. To purchase its approximate 20% interest, Elan invested an additional $3 million into MSRD. The combined $15 million was subsequently used to license research and development technology from Elan to develop Elan's proprietary oral sustained release formulation of fampridine for the treatment of multiple sclerosis. This purchase is recorded as a license payment expense in the consolidated financial statements for the fiscal year ended June 30, 1998. For the years ended June 30, 2001, 2002 and 2003, and the period from March 17, 1995 (inception) to June 30, 2003, MSRD incurred approximately $2.2 million, $2.9 million, $3.2 million, and $24.6 million, respectively, in research and development expenses, which is included as research and development expense in the accompanying statements of operations, of which Acorda funded 80% and Elan funded 20% until June 30, 2002, in accordance with the terms of the original development agreement. Elan's ownership interest in MSRD is reflected as minority interest in the accompanying statement of operations. The minority interest share of the MSRD losses were being funded by Elan, and through June 30, 2002 the Company received $1,279,361 as a reimbursement of this funding. In fiscal 2003, Elan ceased funding its approximately 20% share of its minority interest in MSRD and the Company ceased recognizing the related minority interest benefit resulting in an increase in the Company's ownership interest to 83% pursuant to the original agreement. [from 2003 S-1 IPO application]

The Carnival Wants YOU!

It's time, it's time. The deadline is quickly approaching.

Please enter your submission for the upcoming Carnival of MS Bloggers.

The Carnival of MS Bloggers is for MSers by MSers and encourages participation from all MS Bloggers. That means YOU!

The next Carnival will be hosted here on June 19, 2008. Please submit a post (via blogcarnival or email) from your blog of which you are particularly proud, or which you simply want to share, by noon on Tuesday, June 17, 2008.

Be sure to include a link to your chosen post. Thanks.

4-AP, Fampridine-SR, and Spinal Cord Injury

Previously I asked the question - What is 4-Aminopyridine?
Now I'd like to highlight some research which was conducted regarding it's possible use in Spinal Cord Injury(SCI).

Please note that I am not a science professional. I am merely an individual who likes to conduct research and analyze material.

Early Animal Investigation of 4-Aminopyridine (1987-1990):
Andrew Blight*

• J Neurol Sci, Dec 1987 - Augmentation by 4-aminopyridine of vestibulospinal free fall responses in chronic spinal-injured cats. Blight, Gruner. New York University Medical Center, New York.
• Brain Res Bull, Jan 1989 - Effect of 4-aminopyridine on axonal conduction-block in chronic spinal cord injury. Blight. New York University Medical Center, New York.
• J Neurotrauma, Summer 1991 - The effects of 4-aminopyridine on neurological deficits in chronic cases of traumatic spinal cord injury in dogs: a phase I clinical trial. Blight, Toombs, Bauer, Widmer. Purdue University School of Veterinary Medicine, Indiana.

First Human Clinical Studies supported by CSRO (1990-1992):

Hayes, Blight, Hansebout, et al.

• Paraplegia, Apr 1993 - Preclinical trial of 4-aminopyridine in patients with chronic spinal cord injury. Hayes, Blight, Potter, Allatt, Hsieh, Wolfe, Lam, Hamilton. Parkwood Hospital, University of Western Ontario, London, Ontario, Canada.
• J Neurotrauma, Spring 1993 - 4-Aminopyridine in chronic spinal cord injury: a controlled, double-blind, crossover study in eight patients. Hansebout, Blight, Fawcett, Reddy. McMaster University, Hamilton, Ontario, Canada.
• J Neurotrauma, Aug 1994 - 4-Aminopyridine-sensitive neurologic deficits in patients with spinal cord injury. Hayes, Potter, Wolfe, Hsieh, Delaney, Blight. Parkwood Hospital, University of Western Ontario, London, Ontario, Canada.

In March 1995, Dr. Ron Cohen founded Acorda Therapeutics, Inc. to develop therapeutic products for spinal cord injury and other central nervous system disorders. In 1995, The Canadian Spinal Research Organization (CSRO) entered into a licensing agreement with Acorda Therapeutics whereby Acorda obtained the rights from CSRO (patent originally obtained by Hansebout and Blight) to develop fampridine for therapeutic use in SCI. To start the more rigorous and official FDA approval process and preclinical development, Acorda also submitted an Investigational New Drug application (IND) in 1995.

• J Neurotrauma, Mar 1997 - Effects of 4-aminopyridine on motor evoked potentials in patients with spinal cord injury. Qiao, Hayes, Hsieh, Potter, Delaney. University of Western Ontario, London, Canada.
• Neuroscience, Mar 1997 - Differential effects of low and high concentrations of 4-aminopyridine on axonal conduction in normal and injured spinal cord. Shi, Blight. University of North Carolina at Chapel Hill.
• Exp Neurol, Dec 1997 - Conduction block in acute and chronic spinal cord injury: different dose-response characteristics for reversal by 4-aminopyridine. Shi, Kelly, Blight. University of North Carolina at Chapel Hill.
• Spinal Cord, Mar 1998 - Sustained improvements in neurological function in spinal cord injured patients treated with oral 4-aminopyridine: three cases. Potter, Hayes, Hsieh, Delaney, Segal. Parkwood Hospital, London, Ontario, Canada.

Between 1993-1995, Joseph G Masterson of London, UK and Michael Myers of Athlone, IE applied for U.S. Patents related to the sustained-released technology for Fampridine-SR (slow-release fampridine/4-aminopyridine). These patents were assigned to Elan Corporation, plc. The three patents were awarded on December 6, 1994, July 30, 1996, and December 3, 1996.

In January 1997, Acorda entered into another licensing agreement with Elan Corporation plc of Athlone, Ireland, to develop Fampridine-SR for treatment of Spinal Cord Injury. Elan will continue to manufacture and then supply Fampridine-SR to Acorda.

From the February 20, 1997 Announcement:

Dr. Cohen [President and CEO of Acorda] added: "We are delighted to be working with Elan on the development of fampridine for SCI. Elan is a world-leader in drug formulation technology, and we believe that their unique sustained-release formulation of fampridine is a significant advance in administering this compound in chronic SCI. In addition, Elan has superb expertise in leading-edge neurological drug development through their Athena Neurosciences division, which complements Acorda’s teams of world-leading scientists and clinicians in the areas of spinal cord repair and regeneration. Elan’s patented formulation of fampridine also is complementary to Acorda’s patents, which relate to uses of 4-AP in spinal cord injury."

Michael Sember, Vice President of Planning, Investments and Development at Elan, said: "Elan is most pleased to be collaborating with Acorda. We believe that this collaboration offers great potential to accelerate the clinical development of fampridine, as Elan continues to focus on its target markets such as MS, and Acorda carries the product forward for SCI." Mr. Sember has been elected to Acorda’s board of directors as part of the announced deal.

On June 2, 1997, Fampridine-SR was awarded Orphan Drug Designation for treatment of Spinal Cord Injury. In October 1997, Acorda Therapeutics was awarded $2M Advanced Technology Program (ATP) for Spinal Cord Regeneration Project.

Phase II Trials and Pharmacokinetics Studies (1997-2001):
Hayes, Potter, Hansebout, Blight, et al.

• J Neurotrauma, Oct 1998 - Randomized double-blind crossover trial of fampridine-SR (sustained release 4-aminopyridine) in patients with incomplete spinal cord injury. Potter, Hayes, Segal, Hsieh, Brunnemann, Delaney, Tierney, Mason. Parkwood Hospital, University of Western Ontario, London, Canada.
• Spinal Cord, Jan 2000 - Intravenous infusion of 4-AP in chronic spinal cord injured subjects. Donovan, Halter, Graves, Blight, Calvillo, McCann, Sherwood, Castillo, Parsons, Strayer. The University of Texas Houston Medical School, Houston, Texas.
• J Clin Pharmacol, Apr 2000 - Absorption characteristics of sustained-release 4-aminopyridine (fampridine SR) in patients with chronic spinal cord injury. Segal, Hayes, Brunnemann, Hsieh, Potter, Pathak, Tierney, Mason. Department of Veterans Affairs Medical Center, Long Beach, California.
• Spinal Cord, Dec 2000 - Intrathecal administration of 4-aminopyridine in chronic spinal injured patients. Halter, Blight, Donovan, Calvillo. Baylor College of Medicine, Houston, Texas.
• J Neurotrauma, Aug 2001 - Effects of 4-aminopyridine on motor evoked potentials in patients with spinal cord injury: a double-blinded, placebo-controlled crossover trial. 26 patients. Wolfe, Hayes, Hsieh, Potter. University of Western Ontario, London, Canada.
• J Clin Pharmacol, Apr 2003 - Pharmacokinetics of an immediate-release oral formulation of Fampridine (4-aminopyridine) in normal subjects and patients with spinal cord injury. Hayes, Katz, Devane, Hsieh, Wolfe, Potter, Blight. University of Western Ontario and Lawson Health Research Institute, London, Ontario, Canada.
• Clin Neuropharmacol, Jul-Aug 2003 - Pharmacokinetic studies of single and multiple oral doses of fampridine-SR (sustained-release 4-aminopyridine) in patients with chronic spinal cord injury. Hayes, Potter, Hansebout, Bugaresti, Hsieh, Nicosia, Katz, Blight, Cohen. University of Western Ontario and Lawson Health Research Institute, London, Ontario, Canada.
• Arch Phys Med Rehabil, Jan 2004 - Pharmacokinetics and safety of multiple oral doses of sustained-release 4-aminopyridine (Fampridine-SR) in subjects with chronic, incomplete spinal cord injury. Hayes, Potter, Hsieh, Katz, Blight, Cohen. University of Western Ontario and Parkwood Hospital, London, Canada.
• Spinal Cord, Feb 2007 (epub Jun 2006) - Phase 2 trial of sustained-release fampridine in chronic spinal cord injury. Cardenas, Ditunno, Graziani, Jackson, Lammertse, Potter, Sipski, Cohen, Blight. University of Washington, Seattle.

In August 2003, Acorda entered an Amended & Reinstated License Agreement with Canadian Spinal Research Organization (CSRO) for SCI.

Discussion of Clinical Trials and use of Fampridine in SCI & MS

• Curr Opin Investig Drugs, Nov 2000 - Fampridine Acorda Therapeutics. Darlington. University of Otago, Dunedin, New Zealand.
• Curr Opin Investig Drug, Jun 2001 - Acute spinal cord injury: pharmacotherapy and drug development perspectives. Blight, Zimber. Acorda Therapeutics Inc., Hawthorne, New York.
• CNS Drug Rev, Winter 2004 - The use of 4-aminopyridine (fampridine) in demyelinating disorders. Hayes. University of Western Ontario, London, Ontario, Canada.
• J Neurotrauma, Mar-Apr 2006 - Clinical trials in spinal cord injury. Blight, Tuszynski. Acorda Therapeutics, Hawthorne, New York.
• Mult Scler, Apr 2007 - Fampridine-SR in multiple sclerosis: a randomized, double-blind, placebo-controlled, dose-ranging study. Goodman, Cohen, Cross, Vollmer, Rizzo, Cohen, Marinucci, Blight. University of Rochester, Rochester, New York.
• Expert Rev Neurother, May 2007 - Fampridine-SR for multiple sclerosis and spinal cord injury. Hayes. University of Western Ontario, London, Ontario, Canada.

Phase III Clinical Trials of Fampridine-SR in Treatment of SPI:

• June 28, 2002 - Acorda Therapeutics announced today that it has begun two Phase 3 clinical studies of its lead product, Fampridine-SR, in chronic spinal cord injury.
• April 14, 2004 - Acorda Therapeutics announced today initial results of both a Phase 2 clinical trial of its lead product candidate, Fampridine-SR, in people with multiple sclerosis (MS), and two Phase 3 trials in people with chronic spinal cord injury (SCI). Data from the MS trial showed a strong positive trend in improvement of walking speed and a significant improvement in leg muscle strength, the trial’s primary and secondary endpoints. Data from one of the two SCI trials showed a strong positive trend in a primary endpoint of reducing muscle spasticity, but neither SCI trial achieved statistical significance in its primary endpoints. Acorda plans to meet with the U.S. Food and Drug Administration (FDA) to discuss a potential Phase 3 trial of Fampridine-SR in MS and further development for SCI.

After the disappointing results of the Phase III SCI trials, Acorda put their Fampridine-SR and SCI project on hold to focus more resources on the Fampridine-SR and MS project.

*Brief Bio of Andrew Blight:

Andrew R. Blight, Ph.D., has been our Chief Scientific Officer since January 2004 and previously served as our Executive Vice President, Research and Development from 2000 to 2004, and Vice President, Research and Development, from 1998 to 2000. Prior to joining Acorda, Dr. Blight spent approximately six years as Professor and Director of the Neurosurgery Research Laboratory at the University of North Carolina at Chapel Hill. Dr. Blight held prior academic positions at Purdue University and New York University. Dr. Blight is a leader in SCI pathophysiology research and has made several important contributions to the field, particularly on the role of demyelination in SCI. He also pioneered the therapeutic application of 4-AP in SCI animal models and in human clinical trials. Dr. Blight is a member of the editorial board of the Journal of Neurotrauma and has served as a member of the NIH NSDA review committee. He was previously Secretary, Treasurer and Vice President of the National Neurotrauma Society. Dr. Blight received his B.S. in Zoology and his Ph.D. in Zoology/Neurobiology from the University of Bristol, U.K.

Next time, I'll discuss more on the research regarding Fampridine-SR and MS.

Flag Day, Graduation, Ethiopia

The “Stars and Stripes”, the official National symbol of the United States of America was authorized by congress on that Saturday of June 14, 1777 in the fifth item of the days agenda. The entry in the journal of the Continental Congress 1774-1789 Vol. Vlll 1777 reads “Resolved that the flag of the thirteen United States be Thirteen stripes alternate red and white: that the union be thirteen stars, white in a blue field, representing a new constellation.”

[from The National Flag Day Foundation]

This morning I attended the graduation ceremonies for one of my high school horn students. She had received an award and each year the recipient of that award is invited to perform at graduation. So a brave hornplayer, Leslie, followed the valedictorian's speech and the commencement speaker by performing Eugene Bozza's Chant Lointain for Horn and Piano. I played the piano part. She rocked!!

One interesting thing that I noted occurred near the beginning of the proceedings as the choir sang the National Anthem. All heads were directed at the humongous flag hung on the gymnasium wall, but maybe only a third of the attendees had hand over heart. Not even all of the faculty members made this small gesture. Perhaps observing whether someone places his right hand across his chest has become less a symbol of patriotism and more one of cultural indoctrination. I think that it has less to do with respect than it does outward signs of conformity.

A second interesting tidbit came during the invocation. First an official school invocation was read; it was also printed in the program. Then three students read verses from three texts. One young man chose a verse from Joshua in the Old Testament of the Bible. The verse chosen by a second young man was recited in the original Sanskrit before he provided the translation. Then a young woman recited a Hebrew verse and it's translation. An inclusive collection of faiths and beliefs represented.

Then the kicker. As the Head Master, this is a private school, was sharing bits about the graduating class he mentioned all of the college applications, all of the acceptances, all of the honors and scholarships. But the one he saved for last was the announcement of a senior who had been presented her commission to attend the United States Military Academy at West Point.

That honorable graduate is none other than my horn student, Leslie. Way to go girl!!

In the afternoon, my Sweetie and I attended a graduation party for the son of one of his co-workers. What a party that was! Wonderful bounty of Ethiopian cuisine, including a traditional honey 'beer' made fresh by the host. Did I mention food? Lots and lots of food.

Later in the evening - I believe many guests were staying the night - we shot some pool and enjoyed music of which neither of us understood a word. The father of the graduate played some music videos in the background which showed copious examples of traditional Ethiopian-style dance. Well, can you see where this is leading?

A drink (coke) was taken out of my hand while I sat in a cozy armchair and I was recruited to join the dancing. OK. I don't dance. Never have really. But many, many, many eyes were on us in that grand basement. So I did my best at replicating the shoulder-shrug/shake and arms bowed just so of a native Ethiopian woman. Out came the video cameras I'm embarrased to say and much laughter bounced around the room. I even grabbed my Sweetie to share in the embarrassment. I'm afraid their friends and family will be talking about the party during which the only non-Africans joined the dance.

Now tell me honestly. Does it matter that in one day I celebrated American patriotism, Christian scripture, original Hindi Sanskrit, Hebrew Torah, and the fellowship of a mix of Muslims and Christians? Such is life near the Nation's Capital.

Toto. We are definitely not in Kansas, I mean Oklahoma, any more.

What is 4-Aminopyridine?

According to Wikipedia:

4-Aminopyridine is an organic compound with the formula H2NC5H4N. The molecule is one of the three isomeric amines of pyridine. It is used primarily as a research tool and is helpful in characterizing subtypes of potassium channel. 4-Aminopyridine is prepared by the decarbonylation of pyridine-4-carboxyamide.

According to Extoxnet PIP (dated June 1996):

4-Aminopyridine, a pyridine compound, is an extremely effective bird poison. It is one of the most prominent avicides. It is registered with the EPA for use against red-winged blackbirds, blackbirds in agricultural fields, grackles, pigeons, and sparrows around public buildings, and various birds around livestock feeding pens. Avitrol repels birds by poisoning a few members of a flock, causing them to become hyperactive. Their distress calls signal other birds to leave the site. Only a small number of birds need to be affected to cause alarm in the rest of the flock. After one alarming exposure, birds will usually not return to treated areas. Avitrol is available as grain baits or as a powder concentrate.

According to Multiple Sclerosis Encylopaedia:

4-aminopyridine (also known as 4-AP and Fampridine) is a drug that blocks the potassium channels in neurons. This effectively improves the transmission of nerve impulses down damaged axons. It does not replace damaged myelin but users of 4-aminopyridine report dramatic improvement in a number of symptoms especially paraesthesia. It should be born in mind that this is an experimental drug and the side-effects are uncertain. Dosages should be carefully regulated as potassium is a chemical that is used extensively in other parts of the body including heart functions.

Agriculturally, 4-AP is used as an extremely effective bird poison sold under the brand name Avitrol. It is highly toxic to all mammals including humans if dosages are exceeded, and, as an experimental drug, recommended dose data is unavailable.

A slow release formulation of 4-aminopyridine is supplied by the Irish drug company, Elan Corporation, and is currently being tested by Acorda in two phase II trials in the US. It is currently awaiting authorisation by the US Federal Drug Agency (FDA).

Actually, Acorda Therapeutics recently announced Positive Data from their Second Phase III Trial of Fampridine-SR on Walking Ability in People with Multiple Sclerosis. Fampridine-SR is a proprietary slow-release formula of 4-aminopyridine. I'll be taking a closer look at how Acorda is aiming to bring this drug as an FDA-approved option to MS patients worldwide.

Researchers have been looking into the effects of demyelination on nerve conduction for many decades. Here is a sampling of earlier published papers related to conduction, demyelination, ion channels, 4-AP and MS.

Early Research in London, UK (1969-1983):
Bostick, McDonald, Rasminsky, Sears, Sheratt.

• Nature, Jan 1969 - Effect of demyelination on conduction in the central nervous system. McDonald, Sears.
• J Physiol, Apr 1970 - Effect of a demyelinating lesion on conduction in the central nervous system studied in single nerve fibres. McDonald, Sears.
• J Physiol, Aug 1971 - Internodal conduction in normal and demyelinated mammalian single nerve fibres. Rasminsky, Sears.
• Br Med J, Dec 1972 - Temperature change and multiple sclerosis. McDonald, Sears.
• Arch Neurol, May 1973 - The effects of temperature on conduction in demyelinated single nerve fibers. Rasminsky.
• Nature, Oct 1976 - Continuous conduction in demyelinated mammalian nerve fibers. Bostock, Sears.
• Nature, July 1978 - Overcoming conduction failure in demyelinated nerve fibres by prolonging action potentials. Bostock, Sheratt, Sears.
• Neurology, Sep 1978 - The pathophysiology of demyelination and its implications for the symptomatic treatment of multiple sclerosis. Sears, Bostock, Sheratt.
• Nature, Feb 1980 - Effects of 4-aminopyridine on normal and demyelinated mammalian nerve fibres. Sheratt, Bostock, Sears
• J Physiol, 1981 - The effects of 4-aminopyridine and tetraethylammonium ions on normal and demyelinated mammalian nerve fibres. Bostock, Sears, Sherratt.
• J Physiol, July 1983 - Potassium channel distribution in spinal root axons of dystrophic mice. Bostock, Rasminsky.
• J Physiol, Oct 1989 - Functional consequences of demyelination. Rasminsky, Sears.

1983: First clinical study of 4-AP in MS, effects on visual function

• J Neurol Sci, Aug-Sep 1983 - Effects of 4-aminopyridine in patients with multiple sclerosis. 10 patients. Jones, Heron, Foster, Snelgar, Mason. University of Keele, Staffordshire, England.

Early Research in New England, USA (1977-1994):
Bowe, Kocsis, Targ, Waxman, et al.

• Arch Neurol, Oct 1977 - Conduction in myelinated, unmyelinated, and demyelinated fibers. Waxman.
• Brain Res, Aug 1980 - Effects of 4-aminopyridine on the frequency following properties of the parallel fibers of the cerebellar cortex. Kocsis, Malenka, Waxman.
• Exp Neurol, Mar 1983 - Effects of 4-aminopyridine on rapidly and slowly conducting axons of rat corpus callosum. Preston, Waxman, Kocsis.
• J Neurophysiol, Aug 1983 - Maturation of mammalian myelinated fibers: changes in action-potential characteristics following 4-aminopyridine application. Kocsis, Ruiz, Waxman.
• Nature, Aug 1983 - Long-term regenerated nerve fibres retain sensitivity to potassium channel blocking agents. Kocsis, Waxman.
• Exp Brain Res, 1985 - Aminopyridine-sensitivity of spinal cord white matter studied in vitro. Kocsis.
• Brain Res, Mar 1985 - 4-Aminopyridine leads to restoration of conduction in demyelinated rat sciatic nerve. Targ, Kocsis.
• Neurology, Jan 1986 - Different effects of 4-aminopyridine on sensory and motor fibers: pathogenesis of paresthesias. Kocsis, Bowe, Waxman.
• Neurosci Lett, Mar 1987 - Functional differences between 4-aminopyridine and tetraethylammonium-sensitive potassium channels in myelinated axons. Kocsis, Eng, Gordon, Waxman.
• Ann Neurol, Aug 1987 - Physiological effects of 4-aminopyridine on demyelinated mammalian motor and sensory fibers. Bowe, Kocsis, Targ, Waxman. Brown University, Providence.
• J Neurophysiol, Dec 1988 - Development of 4-AP and TEA sensitivities in mammalian myelinated nerve fibers. Eng, Gordon, Kocsis, Waxman. Yale University School of Medicine, New Haven.
• J Neurol Sci, June 1989 - Demyelination in spinal cord injury. Waxman. Yale University School of Medicine, New Haven.
• J Neurotrauma, Mar 1992 - Demyelination in spinal cord injury and multiple sclerosis: what can we do to enhance functional recovery? Waxman. Yale University School of Medicine, New Haven.
• J Neurotrauma, Spring 1993 - Aminopyridines and the treatment of spinal cord injury. Waxman. Yale University School of Medicine, New Haven.
• Res Publ Assoc Res Nerv Ment Dis, 1993 - Pharmacological modification of axon membrane molecules and cell transplantation as approaches to the restoration of conduction in demyelinated axons. Kocsis, Black, Waxman. Yale University School of Medicine, New Haven.
• Prog Brain Res, 1994 - Enhancement of action potential conduction following demyelination: experimental approaches to restoration of function in multiple sclerosis and spinal cord injury. Waxman, Utzschneider, Kocsis. Yale University School of Medicine, New Haven.

Early Research in Chicago, USA (1974-1991):

Schauf, Davis, Stefoski, et al.

• J Neurol Neurosurg Psychiatry, Feb 1974 - Impulse conduction in multiple sclerosis: a theoretical basis for modification by temperature and pharmacological agents. Schauf, Davis.
• J Pharmacol Exp Ther, 1976 - Aminopyridines and sparteine as inhibitors of membrane potassium conductance: effects on Myxicola giant axons and the lobster neuromuscular junction. Schauf, Colton, Colton, Davis.
• Adv Neurol, 1981 - Approaches to the development of pharmacological interventions in multiple sclerosis. Davis, Schauf.
• Experientia, Feb 1987 - Selective blockade of components of potassium activation in Myxicola axons. Chauman, Schauf, Davis, Stefoski. Rush Multiple Sclerosis Center, Chicago.

1987-1991: Series of Clinical Studies of 4-AP in MS, effects on motor function

• Ann Neurol, Jan 1987 - 4-Aminopyridine improves clinical signs in multiple sclerosis. 12 male heat-sensitive patients. IV treatment. Stefoski, Davis, Faut, Schauf. Rush Multiple Sclerosis Center, Chicago.
• Ann Neurol, Feb 1990 - Orally administered 4-aminopyridine improves clinical signs in multiple sclerosis. 20 heat-sensitive male patients. Davis, Stefoski, Rush. Rush Multiple Sclerosis Center, Chicago.
• Neurology, Sep 1991 - 4-Aminopyridine in multiple sclerosis: prolonged administration. 17 heat-sensitive male patients. Stefoski, Davis, Fitzsimmons, Luskin, Rush, Parkhurst. Rush Multiple Sclerosis Center, Chicago.

In 1990, Elan licensed from Rush-Presbyterian Hospital in Chicago the Know-How related to fampridine (4-aminopyridine) for treatment of multiple sclerosis.

Research in Amsterdam, The Netherlands (1990-1996):

First large study of 4-AP in MS, broad effects on disability (EDSS) dose and serum level related to efficacy and safety plasma levels variable and difficult to control with Immediate Release form

van Diemen, Polman, Bertelsmann, et al.

• Ann Neurol, Oct 1990 - 4-Aminopyridine in multiple sclerosis.
  Polman, van Diemen, van Dongen, Koetsier, van Loenen, van Walbeek.
• J Chromatogr, Feb 1992 - Determination of 4-aminopyridine in serum by solid-phase extraction and high-performance liquid chromatography. van der Horst, de Goede, van Diemen, Polman, Martens. Free University Hospital, Amsterdam.
• Ann Neurol, Aug 1992 - The effect of 4-aminopyridine on clinical signs in multiple sclerosis: a randomized, placebo-controlled, double-blind, cross-over study. 70 patients. van Diemen, Polman, van Dongen, van Loenen, Nauta, Taphoorn, van Walbeek, Koetsier. Free University Hospital, Amsterdam.
• J Neurol Sci, Jun 1993 - 4-Aminopyridine induces functional improvement in multiple sclerosis patients: a neurophysiological study. 70 patients. van Diemen, Polman, van Dongen, Nauta, Strijers, van Loenen, Bertelsmann, Koetsier. Free University Hospital, Amsterdam.
• Clin Neuropharmacol, Jun 1993 - 4-Aminopyridine in patients with multiple sclerosis: dosage and serum level related to efficacy and safety. 70 patients. van Diemen, Polman, Koetsier, Van Loenen, Nauta, Bertelsmann. Free University Hospital, Amsterdam.
• Arch Neurol, Mar 1994 - 4-aminopyridine in the treatment of patients with multiple sclerosis. Long-term efficacy and safety. 31 patients. Polman, Bertelsmann, van Loenen, Koetsier. Free University Hospital, Amsterdam.
• Neurology, Sep 1994 - The effects of 4-aminopyridine on cognitive function in patients with multiple sclerosis: a pilot study. 20 patients. Smits, Emmen, Bertelsmann, Kulig, van Loenen, Polman. Free University Hospital, Amsterdam.
• Arch Neurol, Nov 1994 - 4-Aminopyridine is superior to 3,4-diaminopyridine in the treatment of patients with multiple sclerosis. 24 patients. Polman, Bertelsmann, de Waal, van Diemen, Uitdehaag, van Loenen, Koetsier. Free University Hospital, Amsterdam.
• Mult Scler, Feb 1996 - Magnetic resonance imaging of epilepsy in multiple sclerosis: a case control study. Implications for treatment trials with 4-aminopyridine. Truyen, Barkhof, Frequin, Polman, Tobi, Hommes, Valk. Free University Hospital, Amsterdam.

Later in September 2003, Acorda Therapeutics entered into agreements with Rush and Elan terminating the Rush license to Elan with mutual releases. In the process Rush granted Acorda worldwide license to the Know-How and Orphan Drug Designation to fampridine for treatment in MS.

More to come...