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Science Article

February 3, 2005

From basic discovery to breakthrough drug

'Determination and persistence' carries a controversial theory to development of drug that prevents inflammation, reduces MS relapse

By BARBARA BERG

There are few more satisfying experiences for scientists than to see their work benefit others. For Dr. Elizabeth Wayner, that gratification came last fall, when the U.S. Food and Drug Administration granted approval for a breakthrough drug to treat multiple sclerosis that is based on a discovery she made more than 15 years ago.

The drug, known as Tysabri®, was created with a method Wayner developed that uses an antibody to prevent the inflammation associated with multiple sclerosis (MS), a sometimes disabling autoimmune disease that strikes the central nervous system.

Tysabri® also may prove beneficial for patients with other autoimmune diseases such lupus, Crohn's disease and rheumatoid arthritis, as well as melanoma, a serious form of skin cancer. The drug is being marketed by Biogen Idec Inc. and Elan Corp.

"I'm thrilled that my research can help prevent suffering," said Wayner, staff scientist and manager of the Antibody Development shared resource. An estimated 400,000 Americans are afflicted with MS, a disease with symptoms ranging from fatigue and numbness to an inability to walk.

The center holds patents for use of antibodies like Tysabri®, and Fred Hutchinson will receive a percentage of the royalties from the sale of the drug, a portion of which will be shared with Wayner. As with any other royalties generated from center inventions, the money will go directly back into the center's research and clinical programs — where it will support other potentially lifesaving discoveries, said Spencer Lemons, vice president for Industry Relations and Technology Transfer.

"The most rewarding thing for us is to see how our research can directly benefit people," he said. "It can take a long time to see the ancillary benefits of a basic research discovery like this one. Our goal is to make it possible for as many discoveries as we can to succeed commercially."

The drug's roots go back to 1988, when Wayner, then a postdoc in Dr. Bill Carter's Basic Sciences Division laboratory, proposed a controversial idea that could explain how immune cells cause the dangerous inflammation behind many incurable autoimmune diseases. Carter's lab studies what is known as the extracellular matrix — the glue that holds the body's cells together. "It's the reason we don't dissolve when we jump into a swimming pool," Wayner explained.

Carter's lab had been studying catcher's mitt-like proteins called integrins found on the surface of cells. Integrins enable cells to adhere to proteins in the extracellular matrix. This adhesion is critical for wound healing, blood clotting and the ability of cells to migrate to places where they are needed as well as to relay important signals to neighboring cells.

Prior to Wayner's joining the Carter lab, it had been known that skin cells or other cells that line the body's organs had these adhesive properties. But Wayner became curious about whether or not blood cells also could adhere to extracellular matrix proteins. In particular she became interested in the surface proteins called receptors that are produced by T cells, a class of white blood cells that help the body defend against infection.

"I had come from a lab that was studying T cells, and I wondered whether they had receptors that would allow them to bind to endothelial cells (cells that line blood vessels) and the extracellular matrix that supports these cells. This would allow them to adhere to and pass through the lining of blood vessels," she said.

The idea was somewhat heretical, Wayner said, because T cells are supposed to stay in circulation in the blood and were traditionally thought to be non-adherent. If T cells could bind to blood-vessel linings, that would give them the foothold needed to migrate out into and adhere to extracellular matrix components present in tissue — the exact definition of inflammation.

"People didn't believe me when I presented the work at meetings," she said. "But it turned out I was right."

Wayner quickly realized the potential value of her finding — for the first time, it might be possible to develop a way to specifically interfere with this process to prevent the inflammation that occurs in many types of diseases. In particular, inflammation is a hallmark of autoimmne diseases — a collection of disorders in which the body's own immune system attacks itself. In the case of MS, T cells inappropriately react against myelin, a protein that coats nervous tissue.

Wayner developed an antibody — a type of immune-system protein that binds exclusively to another protein — that was specific for the T cell-endothelial cell receptor, also known as the alpha 4/beta 1 integrin receptor. This antibody interferes with the T cell's ability to bind to blood-vessel linings.

A short time after she developed the antibody, Wayner left the center to work in the biotechnology industry. She first worked at a local company called Oncogen and at several other places, always discussing the merits of her new technology. In 1994, Wayner returned to the center as a staff scientist.

"Since the work was started here, I always felt that the center should benefit from it," she said.

Fred Hutchinson initially licensed the technology to Cytel, which subsequently sublicensed and eventually assigned the license to Elan in 2000. Later that year, Elan and Biogen entered into an exclusive collaboration to develop, manufacture and commercialize Tysabri®.

Tysabri® reduced the relapse rate in MS patients by more than 65 percent compared with patients who received a placebo. In contrast, the best selling MS drug, Avonex, reduces the relapse rate about half as often.

In patients already taking Avonex, the relapse rate was halved among patients who also were given Tysabri®. Based on these results, the drug manufacturers believe that Tysabri® could soon become the bestselling MS drug.

Wayner said she feels that her experience can be best summed up by the moral of the fable about the tortoise and the hare: Determination and persistence wins the race.

But mostly, she said, "I'm just very happy that this work can be used to benefit the public."

http://www.fhcrc.org/pubs/center_news/2 ... sart1.html

These results seem to show that T only had a positive effect after the first treatment, and has NO effect on EDSS scores.

So what's the point of taking it if it's not going to delay progression?


Expert Opin Pharmacother. 2003 Jun;4(6):999-1001. Related Articles, Links


Is natalizumab a breakthrough in the treatment of multiple sclerosis?

Doggrell SA.

School of Biomedical Sciences, The University of Queensland, QLD 4072, Australia. s_doggrell@yahoo.com

In patients with either relapsing-remitting or secondary-progressive multiple sclerosis, there were fewer new lesions/patient with natalizumab (0.7 and 1.1 with natalizumab 3 and 6 mg/kg every 28 days, respectively) than in the placebo group (9.6 new lesions/patient) over 6 months. There were also fewer relapses in the natalizumab groups than the placebo group. However, there were no changes in the Expanded Disability Status Scale scores in any of the groups. Natalizumab was well-tolerated. Thus, the initial results with natalizumab treatment over 6 months in multiple sclerosis are encouraging.



Neurology. 1999 Aug 11;53(3):466-72. Related Articles, Links


Comment in:
Neurology. 1999 Aug 11;53(3):444-5.

The effect of anti-alpha4 integrin antibody on brain lesion activity in MS. The UK Antegren Study Group.

Tubridy N, Behan PO, Capildeo R, Chaudhuri A, Forbes R, Hawkins CP, Hughes RA, Palace J, Sharrack B, Swingler R, Young C, Moseley IF, MacManus DG, Donoghue S, Miller DH.

Institute of Neurology, London, UK.

OBJECTIVE: To determine the effect of humanized monoclonal antibody against alpha4 integrin (reactive with alpha4beta1 integrin or very-late antigen-4) on MRI lesion activity in MS. METHODS: A randomized, double-blind, placebo-controlled trial in 72 patients with active relapsing-remitting and secondary progressive MS was performed. Each patient received two IV infusions of anti-alpha4 integrin antibody (natalizumab; Antegren) or placebo 4 weeks apart and was followed up for 24 weeks with serial MRI and clinical assessment. RESULTS: The treated group exhibited significantly fewer new active lesions (mean 1.8 versus 3.6 per patient) and new enhancing lesions (mean 1.6 versus 3.3 per patient) than the placebo group over the first 12 weeks. There was no significant difference in the number of new active or new enhancing lesions in the second 12 weeks of the study. The number of baseline-enhancing lesions (i.e., lesions that enhanced on the baseline scan) that continued to enhance 4 weeks following the first treatment was not significantly different between the two groups. The number of patients with acute MS exacerbations was not significantly different in the two groups during the first 12 weeks (9 in the treated group versus 10 in placebo) but was higher in the treatment group in the second 12 weeks (14 versus 3; p = 0.005). The study was not, however, designed to look definitively at the effect of treatment on relapse rate. Treatment was well tolerated. CONCLUSIONS: Short-term treatment with monoclonal antibody against alpha4 integrin results in a significant reduction in the number of new active lesions on MRI. Further studies will be required to determine the longer term effect of this treatment on MRI and clinical outcomes.

Eric, my thoughts:

Tysabri, at least at this point, is not being marketed as improving EDSS scores. Furthermore, that first study merely shows that NEITHER the placebo group nor the treatment group had changes in EDSS scores in that short time frame.

As for the second study, the one year data released by Elan/Biogen should be considered more conclusive since it covers a longer duration. Certainly this study doesn't show that it stops working, just that the second half of this short study showed no difference (e.g., what is to say that differences did not resume the week after the study concluded?)

Thanks Aaron,

I guess I'm just suspicious why they haven't released any results on impact on disease progression or EDSS (or have they and I missed it?), well, whatever they said they're withholding until the 2 year data is released. I don't expect T to improve EDSS scores, but I'd like to see a difference in EDSS scores between the T group and the placebo group over time, i.e., T prevented a worsening in EDSS next to placebo scores. I just found this info and wondered about it and how it fit into the T "picture" I'm trying to build for myself. I guess the other thing I wondered was if T did all of the "work" that it was ever going to do in the first 12 weeks, and at the end of a year, it was the difference in the first 12 weeks that remained as the only difference between the T group and placebo group.

those are all great questions... remember with RRMS studies, even the control group doesn't necessarily drop in EDSS over a short time frame.

As you noted, we're all waiting for EDSS information in the year 2 data to be released sometime in the first half of this year.

On a related aside, tomorrow Biogen has their investor call and will likely update on Tysabri's rollout.

MANAGED CARE January 2005.

TOMORROW'S MEDICINE

Natalizumab has received FDA approval. But as with all approved treatments, questions remain about efficacy and clinical importance compared to existing therapies.

A New Approach for MS

Thomas Morrow, MD


Since the mid-1990s, there has been revolutionary advancement in the understanding of the pathophysiology and treatment of multiple sclerosis. On November 23, the FDA issued an approval letter to Biogen Idec for natalizumab, a totally new approach to the treatment of MS. There are now three immunomodulation classifications available for the routine treatment of MS, including the three interferons, glatiramer acetate, and now a monoclonal antibody.

All of the classes have fundamentally different mechanisms of action. The interferons basically work by shoring up the blood brain barrier, preventing the migration of activated T cells into the central nervous system. Glatiramer acetate works by confusing the immune system into not attacking the CNS and activating protector T cells to actually decrease the inflammatory response within the CNS.

This new product, natalizumab, acts differently.

Managed care implications
It has a WAC price of $1,808 for a 28-day dose. The daily WAC price is nearly $65, compared to approximately $39 for Avenox, Betaseron, and copaxone, and $48 for Rebif when you take into account the 12 versus 13 dispensing units per year.

Natalizumab is also associated with considerable administrative costs, as it is expected to be administered primarily in physician offices and outpatient infusion sites. With Johns Hopkins University, Biogen has been providing educational programs (as is usual with physician-administered drugs) to neurology offices on the intricacies of office-based infusion, including benefit verification, prior authorization procedures, payer coverage policies, and appeal processes. There is instruction on coding and on setting up an infusion suite, and there is a special section devoted to revenue collection and opportunities for the practice. There is no specific HCPCS code for natalizumab, so the nonspecific codes J3490 "Unclassified Drug" or J3590 "Unclassified Biologic" are recommended.

We now have a new development and, in fact, the first entrant from a whole new class of medications available for the prevention of relapses for MS. But managing the patient who is living with MS is still difficult.

If neutralizing antibodies are present, the efficacy of natalizumab will be minimized. There is no test for the antibodies expected in the near future.

There is also the cost associated with natalizumab treatment, especially when administrative costs are considered.

Also, the safety problems of other monoclonal antibodies are well known. Natalizumab has a slight increase in infections and no current evidence of malignancies, but the worldwide experience is limited to a minuscule percentage of the population with MS. In addition, the long term efficacy is unproven in a population that now has open label trial results available for as long as nine years. Finally, there is the real possibility that providers will request combined therapy.

Management possibilities
What can managed care do? There are a number of management possibilities available for this new entrant. The choices are to:

Develop a stepped care approach with one of the interferons and glatiramer acetate as preferred,
Set up a prior-authorization system to validate lack of efficacy with standard therapeutic options before approving this new, more expensive, therapy,
Contract with a specialty pharmacy company (SPC) to avoid giving physicians an incentive to capitalize on the revenue stream,
Implement edits to an AWP discounted reimbursement, similar to what you would pay an SPC,
Screen data sources for dual therapy and challenge them as off label,
Establish a tracking system for relapses and subsequent progression of disability, the true endpoint of this devastating disease,
Contract for or develop a disease management process to maximize the outcome of patients with MS, focusing on preventing the progression of disability and on preventing or managing the comorbid conditions to avoid unnecessary hospitalizations for issues such as uro-sepsis, and
Demand head-to-head trials with existing therapies.
Tysabri's mechanism of action
Natalizumab is being marketed under the name of Tysabri. In early news releases, the company had proposed the name of Antegren, but changed the name before launch.

This compound is the first of several antibodies in the pipeline targeting different steps in the immune dysfunction that leads to the clinical condition we call MS.

The exact mechanism of action by which natalizumab exerts its effects in multiple sclerosis is not fully defined. MS is believed to develop when activated inflammatory cells, including T cells, cross the blood brain barrier. No one is sure how the inflammatory cells are activated, but the result is the presence of highly active inflammatory cells within the CNS causing destruction of the "insulating" myelin sheath around nerves. Once damaged, the nerves cease functioning normally and the neurologic effects become the symptoms of MS.

Before the inflammatory cells can cross into the CNS, they must bind to the lining of the blood vessels, the endothelium. Natalizumab is thought to work by preventing this binding and hence stopping the migration of the damaging cells.

Structurally, natalizumab is a recombinant humanized IgG4κ monoclonal antibody produced in murine myeloma cells. It binds to the α4-subunit of α4β1 and α4β7 integrins expressed on the surface of all leukocytes (except neutrophils) and inhibits the α4-mediated adhesion of leukocytes to their corresponding receptor. These α4 integrins are a family of integrins that include vascular adhesion molecule-1 (VCAM-1), which is expressed on activated vascular endothelium, and mucosal addressin cell adhesion molecule-1 (MadCAM-1), present on the vascular cells of the gastrointestinal tract.

This binding basically disrupts the attachment of leukocytes to the blood vessels and prevents the migration of these activated leukocytes into the inflamed area; in the case of MS this is the central nervous system. Simply put, if the T cells establish a foothold on the endothelium, leukocytes cannot migrate through. Natalizumab prevents the foothold from occurring.

Infusion
The new treatment consists of a dose of 300 mg of natalizumab mixed with 100 mL of 0.9 percent sodium chloride injection, USP, administered during a one-hour infusion every 28 days. As with all proteins, mixing should be done gently to prevent damage to the large protein molecule. The mixed solution must be administered within eight hours. The product has a labeled shelf life of 15 months when unmixed and stored.

There are no dose adjustments for weight. Natalizumab is classified as pregnancy category C and has not been studied in nursing mothers. There were insufficient numbers of patients over 65 to make a recommendation, and the drug has not been studied in patients under age 18.

The most frequently reported serious adverse reactions with natalizumab were infections. According to the package insert the worldwide experience with natalizumab in both controlled and uncontrolled studies is limited to 1,617 total patients with a medium exposure of 20 months.

As is true of virtually all biologics, there are no head-to-head studies against the standard therapies. No meta-analysis published, but from this writer's uneducated observation, it appears that the actual relapse rate reduction is about the same as has been seen with the more proven therapies. Obviously there are no long term efficacy or safety data available.

Neutralizing antibodies
One very bothersome finding is the development of neutralizing antibodies that were, according to the prescribing information, detected in approximately 10 percent of patients receiving natalizumab. This became persistent in 6 percent of patients receiving the medication, so much so that it led to a "substantial decrease in the effectiveness."

In fact, the annualized relapse rate of persistently antibody-positive patients was similar to the annualized relapse rate in patients who received placebo. The assay used during the study was unable to detect low to moderate levels of antibody to natalizumab. The effects of low to moderate levels of antibody are unknown.

Accelerated approval
There is no commercially available neutralizing antibody test available, and the PI does not require its use in clinical practice. This issue appears to be very important to the FDA, as there were numerous requirements in the approval letter, including the development of a screening immunogenicity assay that will detect anti-natalizumab specific antibodies. The requirement is for the developments in the screening assay to be reported to the FDA by March 31, 2007.

This product was approved under the "accelerated approval of biological products" regulations 21 CFR 601.40-46, which allow the use of surrogate endpoints or an effect on a clinical endpoint other than survival or irreversible morbidity as the basis of approval. Other approved therapies have demonstrated improvement in the delay of disability as measured by the Expanded Disability Status Scale (EDSS).

Because of this, the FDA is requiring Biogen to perform adequate and well-controlled studies to verify and describe the clinical benefit attributable to this product. In particular, the FDA is requiring that Biogen verify that the clinical benefit of reduction in exacerbations is sustained with continued administration.

These studies are due September 2005. The FDA is also requiring that Biogen perform a study of the pharmacokinetics of chronically dosed natalizumab in the presence of glatiramer acetate — a portent of possible combination therapy.

This is the first generation of this class of drug. Time and experience with this antibody will demonstrate whether this class is as safe as the existing immunomodulators or if it is worth the premium pricing. That will be the topic of future essays on Tomorrow's Medicine.



Thomas Morrow, MD, is president of the National Association of Managed Care Physicians and vice president and medical director of Matria Health Care. He has 20 years of managed care experience at the payer or health plan level.

http://www.managedcaremag.com/archives/ ... otech.html

New Drug Has MS Sufferers Filled With Hope

Feb 8, 2005 3:48 pm US/Mountain

DENVER (CBS4) Those battling multiple sclerosis know what the illness is both frustrating and unpredictable.

There's now a new treatment available, though, that has many in Colorado afflicted with M.S. filled with optimism.

M.S. is a disease of the central nervous system. One of the many people affected by it is Quentin Rose, who once fancied himself a weekend warrior.

"I can't play hockey anymore, I can't play golf anymore," he said. Except for playing with his dog, his athletic endeavors were brought to a screeching halt one day two years ago.

"I got up that morning to go to work (and) my right leg was dragging a little bit," he said. "(I had) a little weakness in my right arm."

Neurologist Dr. John Corboy with the University of Colorado Health Sciences Center said that brain lesions appear in patients such as Rose who have multiple sclerosis.

"The more lesions you have, (and) more importantly where the lesions are, will lead to various types of disabilities," Corboy said.

Colorado has one of the highest rates of M.S. in the world. Doctors and patients here have often been frustrated by the treatments, CBS4 News reports.

Some treatments come with miserable side effects, and many others are just not very effective. In the past 3 months, however, a new drug, Tysabri (formerly known as Antegren), has hit the market that attacks the disease in an entirely different way.

"This drug will stop white blood cells from entering the brain and spinal cord and (will stop) causing new lesions," Corboy said.

Rose is among the first three patients at the Health Sciences Center to receive this new treatment.

"What is hoped with new therapies is, nothing new will happen, you won't have problems with [your] left leg, you won't have new effects on your arms or other organs," Corboy said.

The slow drip of a new medication is not a cure, but for Rose and others, it is an infusion of hope.

"It's something that will turn the M.S. world upside down on its head," Rose said.

http://news4colorado.com/health/local_s ... 61159.html

Eric,

I certainly share your concern about just how much Tysabri will benefit MS patients.

When I spoke to my wife's neurologist back in December, ( he has been involved in the Tysabri trials here at the MS Clinic for a number of years) he told me that they did not find any improvement in the EDSS scores. He also advised me that it looked like Tysabri would be OK for newly diagnosed, mild MS cases and not for anything beyond that.

There have been a number of Biogen press releases posted here and they of course are used to promote Tysabri. I still have difficulty understanding how this drug got approved so quickly on one year data from 2 of 99 Phase III two year world-wide clinical trials. Based on this initial information, the number of MS patients being switched over to Tysabri is huge, much to the delight of Biogen/Elan. As Arron has stated, there are numerous unanswered questions about this drug and they will remain this way until the two year data is released and patients outside of the clinical trial setting begin to use the medication.

Harry

Interesting comments from a MS-patient.

Tysabri cannibilization of MS ABCRs


"Aggressive cannibilization will occur in the older MS drugs based on their PAST KNOWN poorer efficacy, lessor safety profile, and lacking patient comfort. An informed MSer will USUALLY have the final say over their neuro's recommendation in selecting an MS treatment.

Steroids have only been shown to be a quick temporary form of relief prescribed occasionally for the MSer sufferring an exacerbation or relapse.

Novantrone, as a lower dose cancer chemo infusion has an undesirable safety profile and is occassionally prescribed to worsening progressive MSers. This drug will most likely remain as a bottom tier MS drug and used less often as a last ditch treatment for the progressive MSer in the event Tysabri provides no relief for the advancing MS.

As an MSer who was been prescribed both Betaseron and Avonex during the past 10 years of the entire post-approval history for ALL ABCR MS drugs, I biased each drug's clinical efficacy over KNOWN safety and patient comfort level as well as its actual effectiveness for my MS. BUT, Efficacy wasn't always a major consideration in deciding which of the ABCRs I was to continue therapy on. Why do I mention this? Because the NARROW lower range clinical efficacy of all the existing ABCRS! If any two drugs with a similar mechanism of action had a clinical efficacy difference of 5% or less, I more than likely WOULD chose BETTER COMFORT over very small EFFICACY benefit.

The added edge of higher efficacy in any of the available drugs that SIMILARILLY offered NO further clinical benefit in actually halting or drastically slowing down the disease offered little to override my desire to at least be more comfortable if I was JUST AS LIKELY to suffer relapses anyway. My personal theory here was that if I WAS to be MORE miserable by taking an injectable ABCR MS treatment, I PREFERRED to be MORE comfortable as often as possible while still being stuck feeling miserable with R/R MS.

The ABCRs in order of theoretical fastest to slowest cannibilization by Tysabri:

1. A-vonex>worst patient comfort profile for the R/R MSer as a painful weekly IM injection among all existing ABCRS

2. B-etaseron>slightly less efficacious than most of the leading existing ABCRs with a better comfort profile than Avonex as an SC injectable

3. C-opaxone>different mechanism of action with SC injection, average comfort and similar efficacy to existing ABCRs

4. R-ebif>slightly more efficacious at a higher dosage and better patient comfort than Avonex in self administration for an SC injectable

Not only did Tysabri offer me a greater renewed hope in slowing my advancing MS than any of the current ABCRs, I have regained a much better COMFORT level and higher QUALITY of living by NOT BEING FORCED to suffer ANY more additional discomfort of the past ABCR treatments.

I base my opinion on what I have observed and experienced as an active MSer over the past ten long years. There is no doubt in my mind that any R/R MSer having the least amount of consideration for a much greater chance at a healthier well-being, better quality of life, increased comfort, AND if fairly informed, will ENCOURAGE their physician or specialist to prescribe them Tysabri for MS. "

I am new and a caregiver for my husand who has had a wicked fight w/ MS for over 25 years. He walks, barely, with a cane, has total blindness in r eye and near blindness in l eye. His attacks have been, as one Dr. put it, "doosys". I've been reading where some people saw some difference in there abilities with first treatment. Could it be that someone like my husband, who is barely getting around, may see a more noticable difference compared to some one who is newly diagnosised or just drags a leg occasionally. Could that be the difference that is not being addressed? Granted, if EDSS did not improve, there are worlds of studies going on now with good results on myelin repair. Tysabri may not be the answer, yet. But it may start something new. Betaseron sure opened the door for treatments.

Amelia,

I'm going to presume that your husband has SPMS since he has been fighting this disease for over 25 years. With the symptoms that he is showing, it appears that he has suffered some permanent damage to his myelin/neurons but with MS, this can be something that is very difficult to determine. It varies from patient to patient.

With what we have been told about Tysabri, it delays further damage to the myelin by not allowing certain T cells to cross the blood/brain barrier and cause even more damage. It was not designed to nor is it expected to repair any of the damage that has been done. Having said that, there are many instances where MS patients have tried various medications and ended up with some immediate unexplained positive results. You just don't know how to explain some of this things!

One of positive effects of research in the past few years is that the scientists are just not looking at the immune system to figure this all out. They are looking at hormones, anti-biotics and enzymes and seeing if they might be the answer. As a neuro told me once, he believes that a researcher is going to "stumble" upon some idea while looking at something else and that could be the "magic bullet" that we are all hoping for.

Harry

.
New Drug Shows Breakthrough In Treating Crohn's Disease

http://www.wnbc.com/drmaxgomez/4186643/detail.html
.

No, his neuro still considers him RRMS. But I can see where you are coming from. One thing that happens to him that makes me think that a great deal of his symptoms are not permanent: right before an attack, he gets considerably better. If it's an attack on the legs, his right leg, which drags always, will walk completely normal. Then within 24 to say about 36 hours, the attack hits, that leg! He is totally blind in the R eye. No light or anything. He started seeing out of it all of a sudden one day, then the next day he started losing sight in the left eye. Our belief, and hope, is that the MS is still active, like it just won't let go and the Tysabri or some other drug will stop most of the "eating" that is going on. I know this sounds weird. But he has the classic attack with complete or mostly complete recovery. He went through a 2 year spell in 1996 of having an attack every 4-6 weeks. That is when he lost his ability to walk without a cane and has not ever been able to quite gain that back. Therapy does wonders, but we have Medicare only and it just gets too dogone costly.

Amelia,

Sounds like your husband is really in a battle with the MS!

And you are so right about knowing what medication to choose...not even the docs know what to use in most instances. Like one neuro told a patient in another thread on this forum....."which medication do you want to use...none of them really does very much!" Nothing like a vote of confidence from your neuro!!

Whatever route he chooses, I hope it works out.

Harry

Gary and I were married 11 months when he was kicked in the head by a cow. He was a cowboy. Whiplash with numbness and tingling followed over many weeks. I found out I was pregnant with our first child the first of April and the last of May, I helped him walked to the hospital emergency room. He was sent home with the diagnosis of chemical poisoning and NO treatment. Went back into the hosipital in Aug, same year. Stayed there a month, had spinal cord surgery in the neck region first of Aug. No definited diagnosis. His MS did not show up on test. Eye evoked Response, spinal tap, CAT scans, nothing. After ups and downs and an eight year remission, he injured his back. It started all over again. Added MRI's with no scars. Finally a neur said he had clinical MS. If it resoned to all the treatments, then it must be MS. Finally had ON in left eye. Was blind in Right eye from a welding accident, we thought. Anyway, true diagonsis, started Betaseron not long after that, has had ups and downs, but pretty much okay. He is a fighter. I have seen him fall, get back up, fall again, etc. With many of his attacks, he was paralyed either from the neck down or the waist down. His attacks were never light ones. We only dreamed of "dragging a leg for a day or 2". Now he is on Copaxon, still fighting with whatever exercise he can do. Hoping for something better. Who knows what waits around the corner. I am envious of the newly diagnosised. They have SO much more hope now of leading a near normal life. But I wish them the best and hope they will fight as well.