Day of the Orals

September 30, 2009: The Day of the Orals

Oral disease modifying agents for MS took a further leap today.

1. Merck KGaA (MKGA.Y; MRK) announced that the have filed an NDA with the FDA.

2. The preliminary results from Novartis' (NVS) FREEDOMS trial were released.

FREEDOMS:

This is a phase III, 2-year ex-U.S. randomized, double-blind, placebo-controlled comparing two doses of oral fingolimod (FTY720) and placebo. The primary endpoint was reduction in annualized relapse rate.

- The placebo annualized relapse rate was 0.40 (number of subjects=418);

- Lower dose fingolimod (0.5 mg) was 0.18, representing a 54% reduction (n = 425); and

- Higher dose fingolimod (1.25 mg) was 0.16, representing a 60% reduction (n= 429).

Earlier, the TRANSFORMS study -- a phase III, 1-year, global, randomized, double-blind, double-dummy, avonex (interferon bet-1a intramuscular) - controlled study -- demonstrated a reduction in the annualized relapse rate as well:

- The avonex annualized relapse rate was 0.33 (number of subjects=431);

- Lower dose fingolimod (0.5 mg) was 0.16, representing a 52% reduction (n = 429); and

- Higher dose fingolimod (1.25 mg) was 0.20, representing a 38% reduction (n= 420).

This seems consistent with FREEDOMS and makes sense -- the placebo arm in FREEDOMS had a higher relapse rate than the avonex arm in TRANSFORMS (0.40 vs 0.33) and the fingolimod arms all had an annualized relapse rate of 0.16 - 0.20.

So, how does this compare to cladribine and tysabri (natalizumab)?

CLARITY, a phase III, 2-year, global, randomized, placebo-controlled trial of oral cladribine in two doses vs. placebo revealed:

- The placebo annualized relapse rate was 0.33 (number of subjects=435);

- Lower dose cladribine (3.5 mg/kg) was 0.14, representing a 57.6% reduction (n = 430); and

- Higher dose cladribine (5.25 mg/kg) was 0.15, representing a 54.5% reduction (n= 454).

So, most important the placebo in CLARITY had the same annualized relapse rate as the avonex arm in TRANSFORMS.

AFFIRM was a phase III, global, randomized, double-blind placebo-controlled tria comparing IV (intravenous) tysabri to placebo:

- The placebo annualized relapse rate was 0.74 (number of subjects=315);

- Tysabri (300 mg) was 0.25, representing a 66% reduction (n = 627).

So, what this highlights is the difference in the patient population in different studies (the placebos are different -- annualized relapse rate:

- AFFIRM - 0.74;

- CLARITY - 0.33;

- FREEDOMS - 0.40

and in TRANSFORMS, the comparator was avonex and the annualized relapse rate was 0.33; compare this to REGARD - rebif 0.30 and copaxone - 0.29 and BEYOND - betaseron regular dose - 0.35, betaseron double-dose 0.34 and copaxone - 0.34.

While we are always cautioned not to compare between (or among) trials (how much is this fueled by the pharmaceutical industry?), the comparator in TRANSFORMS (avonex) is in-line with modern clinical trials of the other FDA approved injectable disease modifying agents.

SENTINEL, CLARITY and FREEDOMS do, however, have varied placebo (and supposedly treatment arm if well randomized) characteristics. In the absence of comparative trials (not likely unless government mandated -- and funded?), treatment decisions will need to be made based on potential side effects (and risk taking/aversion behavior by both the neurologist and the patient) and other endpoints (such as disability).

An important preliminary result of FREEDOMS is the fact that the cancer risk may have been overblown in TRANSFORMS, but keep in mind that this is only preliminary and FREEDOMS is ex-U.S., as opposed to TRANSFORMS (being global) and FREEDOMS-II, which is a U.S. study (with a lot more monitoring, as mandated by the FDA).

With the FREEDOMS results, will Novartis be ready to file with the FDA?

Well, Novartis will almost certainly file with the Europeans (European Medicines Agency -- EMEA), but will the FDA accept an ex-U.S. 2 year placebo-controlled trial and a one year active comparator trial, when it clearly wanted more safety data, as required in FREEDOMS II?

I guess we will have to wait and see.

- Dr. Daniel Kantor, MD BSE
Medical Director
Neurologique

info@neurologique.org
www.neurologique.org

Multiple Sclerosis Patient Network (MSPN)

People continue to email and continue to ask questions and continue to want to help others, by our publishing these questions and answers online.

Question:

I viewed your video clips and I thought they were excellent and very informative.

In your clips, you said to “start early, start now…” I started very early by discovering MS very early. I started the combi - RX trial with the NIH . We are studying if takingAvonex and Copaxone together are better than taking just 1 or the other. Each of us is guaranteed at least 1 and probably receives both of them. My friends and Doctor say the medicine is working.

I am interested in your knowledge about cognition and want information about improving my cognition. I’ve research it some and discovered a medicine that could improve cognitive skills. Please tell me if you know any other things that could help me return to being “one of the sharp tools in the work shed…” Here is a website that interests me -http://en.wikipedia.org/wiki/Nootropic

Keep up the good work…,

Answer:

Thank you for the kind and encouraging words. If this is something
that other people want as well, we can continue it in the future at
other meetings (and even in between).

CombiRx is finally finished recruiting and we should be seeing results
in the next 2 - 3 years. Based on the earlier safety data, I have been
using combined glatiramer acetate (copaxone) and beta interferons
(avonex, betaseron, rebif and soon: extavia) with a lot of success
(but this is obviously uncontrolled).

As you point out, MS is a lot more than movement and walking.
Cognition (memory or thinking) may be affected by MS as well and we
are trying to figure out better strategies to deal with this troubling
symptom.

For more about the causes of cognitive problems in MS (it is not
always as simple as blaming the MS plaques themselves), see:

http://www.healthcentral.com/multiple-sclerosis/c/428/57171/cognitive

This is why it is so important to talk to your neurologist to figure
out what is causing your symptoms. You may also want to be seen by a
neuropsychologist.


In another post, I reviewed ways of treating these symptoms, see:

http://www.healthcentral.com/multiple-sclerosis/c/428/58391/cognitive


The website you point out reviews many different medications to help
cognition, as well.

Also, don't forget other techniques, besides expensive
pharmaceuticals, such as yoga, tai chi, crosswords and sudoku.

Question:

Two of my most painful and distressing sx are TN and the MS Hug. They often appear together. Is there any known connection between them and, more importantly, is there any treatment for them? In the meantime I simply try deep breathing and swimming to get some relief.

Thank you for relating to my question.

Answer:

This is an excellent question -- the "MS hug" is a symptom of
transverse myelitis (TM) and trigeminal neuralgia (TN) is the shooting
pain that can come from MS lesions in various places (including
possibly the high cervical spinal cord).

It sound slike both of them come on (are uncovered) when you are
stressed or overheated and this may explain why swimming helps. The
deep breathing may be useful, not only in making it easier to breathe
when you have tightness around your chest or abdomen, but may also
relax you. The relationship between MS and stress is a tricky one, but
we do know, at the very least, that stress can worsen MS symptoms.

A pseudorelapse means that there is not actually new inflammation or
MS activity, but that older symptoms are uncovered. This is usually
because of an overheating of the nerves -- for more about heat
sensitivity and it causing something called Uhthoff's phenomenon --
see:

http://www.medhelp.org/posts/Multiple-Sclerosis-MS/MS-Symptoms-and-being-sick/show/756505


Neurologists treat TN and TM with symptomatic medications, like
oxcarbazepine (trileptal), other epilepsy drugs (not because you have
seizures) and even antidepressants. When these symptoms are new or
especially severe, neurologists may consider steroids (intravenous
methylprednisolone, intramuscular or subcutaneous ACTH or high dose
oral prednisone). I also use a medication called compounded
4-aminopyridine (soon to be available as Fampridine SR by Acorda
Therapeutics and hopefully another similar medication Nerispirdine by
Sanofi-Aventis many years from now). This medication prolongs action
potentials (electricity in the nerves) and thereby allows a greater
statistical chance for electrical nerve conduction to proceed. At
first some people with TN complain that their pain worsens because
their nerves are working better, but soon the nerves actually do work
better and the trigeminal neuralgia is better controlled.

Sometimes patients are given intravenous (IV) phenytoin (dilantin) or
fosphenytoin to break a severe attck of TN.


I reviewed medictions above, but there are, of course, other
therapeutic options, such as acupuncture.

Question:

Thanks for being active in this seminar.

Question: Are there drugs, especially tablets in the pipeline for people like me with P.P.M.S.? I am disabled, and feel left on the side line.

Answer:

Unfortunately all of the currently FDA approved disease modifying
medications work mostly in relapsing remitting MS (RRMS).

We often use chemotherapies in the treatment of progressive MS -- such
as, mitoxantrone (novantrone), cyclophosphamide (cytoxan), etc.

More recently there have been trials with dirucotide (MBP8298), with
unfortunately negative results.

There are ongoing trials with FTY720 (fingolimod) and many of us
believe that rituximab (rituxan) works in progressive MS (despite the
clinical trial) -- we will see what happens with ocrelizumab.

At Neurologique, we are working diligently on developing a medication
for progressive MS; once clinical trials commence, we will be sure to
announce this prominently.

Question:

We live in the Seattle area. My daughter was 25 at the time she was
diagnosed with MS. After several years of Avonex, she finally found a
"Lyme" dr. who tested her & says with 90 percent certainty that she has Lyme
Disease. Symptoms are much the same; several different Lyme tests were done
to confirm the Lyme diagnosis.

Does Avonex & doxycycline (sp?) make a bad mix? Does revving up her immune
system with the Avonex & taking the antibiotic at the same time to fight off
the Lyme infection make any sense or detrimental in any way? She is
particularly mad that she's been on the MS drug for about 5 years and it may
have been Lyme that whole time. The expense of the MS drug has not been easy
to deal with and she's had to quit jobs shortly after starting them due to
the fact that some insurance companies don't cover her drug and she didn't
know the drug wouldn't be covered until after she got on their insurance and
checked with the carrier only to find out what drugs were or were not
covered.

Answer:

Thank you for the question. This situation does sound frustrating.

I am not sure why the diagnosis of Lyme disease was raised. While Lyme disease is in the differential diagnosis (other things we think about when evaluating a patient), it is often distinguishable from MS.

What type of '"Lyme" dr' was this? Why were several tests needed?

There is no known interaction between Avonex and doxycyline. Avonex does not "rev up" the immune system, so I may be misunderstanding part of your question. Doxycycline should only be used for 4 weeks or less, as it does not seem to be effective over longer periods, see:

http://www.neurology.org/cgi/rapidpdf/01.wnl.0000265517.66976.28v1.pdf

and the patient summary at:

http://www.aan.com/practice/guideline/uploads/243.pdf

Doxycycline also may cause side effects, like abdominal issues, photosensitization (skin is sensitive to light), high pressure in the spinal fluid (pseudotumor cerebri) and antibiotic resistance (a huge public health issue).

http://www.medhelp.org/posts/Multiple-Sclerosis-MS/Sunburn-Sensation-al-over/show/775494

On the other hand, there is some data that doxycycline may help MS by its effects on the immune system, but this is not a reason to start taking any medication (there are many drugs being proven or disproven every year and there is a natural tendency to jump at taking common drugs for MS without full evidence of safety).

[The problem with taking medications for MS that do not have large amounts of data is that the immune system is a double-edged sword and so you may actually be hurting yourself].

I am sorry about the financial frustration your daughter has been going through. Most of the companies have financial assistance programs and they can usually help verify insurance coverage. In terms of her frustration, though, I am not sure that she should discard the MS diagnosis in favor of Lyme disease (so it was not in vain).

What does her MS neurologist think about all this?

Keep the questions coming.

- Dr. Daniel Kantor, MD BSE
Medical Director
Neurologique

info@neurologique.org
www.neurologique.org

Getting smarter

Is getting smarter, getting better?

RebiSmart™ is the new autoinjector developed for Rebif, interferon beta-1a subcutaneous (s.c.) made by Merck KGaA and EMD Serono.

This revolutionary autoinjector is unlike anything you have ever seen or even imagined.

Let’s start with standard autoinjectors: They are available for the three subcutaneous (s.c.) MS disease modifying agents (Betaseron, Copaxone, Rebif and soon, Extavia). Avonex is intramuscular (i.m.) and does not have an autoinjector for technical reasons, but one is in development.

The autoinjectors share a lot in common: the basic shape, you don’t see the needle until the end and a spring loaded system. Patient concerns are also similar: the noise of the injection. There are some differences: patients generally do not like the new Betaject Lite, because: it is harder to push the button, the handle is thicker, you can’t easily change the depth (you need to get different heads for each of the 3 depths) and you have to press it deeper into the skin and the needle seems to go into the muscle.

The new RebiSmart blows away the competition in terms of avoiding seeing the needle, consistency of injection and being able to verify compliance. It is much fancier, heavier and cooler.

Yes, it is the “iPhone” of autoinjectors, but is it really worth it?

It is already available in Europe and Canada and is undergoing testing in the United States in order to seek FDA approval, but can’t we find a better use of these pharmaceutical dollars?

The RebiSmart works as follows:

1. You load a week’s supply of medicine into the machine (it is a machine and not a piece of plastic). The medicine is contained in a non-refrigerated vial (with no needle attached).

2. You push a covered needle system into the unseen vial. You don’t touch or see the needle.

3. You then place the whole rectangular device on the area of the skin you want to inject. You can only inject your skin because there is a special skin sensor.

4. You press a button on top and the needle silently enters your subcutaneous fat (under the skin).

5. Once the light stops flashing, you can take the machine away from your body.

6. You place the cap at the part where the needle is and it is reinserted without you seeing our touching the needle.

The LCD screen takes you through these steps and won’t let you proceed unless you do them correctly. You can even see a calendar with the dates you injected. The problem is that the screen is too small and the colors used in the calendar are black and green and it is hard for people with low contrast sensitivity to make out the difference between these colors. If someone drops the autoinjector (rather, when someone drops it), how will anyone feel comfortable injecting what may contain a broken glass medicine container?

You can set the speed of the needle entering your skin and the speed of the medication going in your body. The whole system is rectangular, as wide as a Blackberry but as tall as a Palm Pilot and the thickness of 2 Palm Treos (is that confusing enough?). It has a nice weight to it and a solid feel. This may be better for people with tremors because there is no narrow fulcrum (there is a wide base) and the weighting might actually be a physical and occupational therapy treatment for the tremors.

If the neurologist is patient enough, she can load the injection information into the computer and verify compliance. This may be useful in discussions on whether this is the right medicine for you. If you are missing a lot of your injections, it doesn’t matter how good the medicine (or the autoinjector) is, it may not be the right one for you. It would be nice to have a beeping reminder if you haven’t injected in 3 or 4 days.

So, how is Novartis going to answer this with their Extavia autoinjector?

Well, Rebif sold against Betaseron its convenience in that there were so few steps. This is definitely not going to be the case anymore. Merck KGaA is coming out with a disposable needle cover for Rebif, so this may be a simpler, if less technologically advanced, option.

So, is hi-tech better?

What do you think?

- Dr. Daniel Kantor, MD BSE
Medical Director
Neurologique

info@neurologique.org
www.neurologique.org

Open letter to Oprah

Dear Oprah,

I was concerned with inaccuracies in the Montel Williams MS (multiple sclerosis) story (08/04/09).

Dr. Oz makes a dramatic demonstration of damaged nerves using an insulated wire. While this made for good television, it was medically incorrect. He asserts that the wire is akin to the nerves in the arms. Loss of myelin (the sheath covering the nerves) in the arms is completely distinct from the loss of myelin in MS.

MS affects the central nervous system (CNS), which includes the brain, optic nerves (nerves to the eyes) and spinal cord (except the lumbar or lower spine). Dr. Oz, on the other hand, demonstrated loss of myelin (demyelination) of the peripheral nervous system (PNS). The cells that make the myelin in the CNS are called oligodendrocytes, while the cells that make myelin in the PNS are called Schwann cells.

This distinction is crucial in not confusing your viewers.

Loss of myelin in the PNS is usually termed "peripheral neuropathy." When viewers are given misleading information, it delays their care and may lead to accumulation of disability.

An example of this was when a 72 year-old man came to see me because he was told that he had "demyelination" and his friends were seeing me because of MS. This gentleman did not need to drive 4 hours to see me only to find out that he has demyelination of the PNS, in other words peripheral neuropathy. Peripheral neuropathy is completely distinct from MS and is treated completely differently.

This confusion further delayed his care.

I also took exception to the comments of MS being "life threatening." MS is a lifetime diagnosis (note, I do not use the word "disease") -- it is not "lifelong," since that makes life sound long and arduous. It is "lifetime" like the cable channel by that name -- even when the TV is off, it is still going on in the background and like the cable station, even when you are not facing it, you need to pay the bills. MS does not significantly affect longevity.

It frightened a lot of people (patients, carepartners, friends and family) for your show to suggest otherwise. Instead of frightening your viewers, they should be educated by your guests and you.

You will then be able to attain your potential for making a true difference in people's lives.

I invite you to continue your education regarding MS and other neurological diagnoses, by visiting: www.neurologique.org and I would be delighted to further explain to you and your viewers the patient-centered approach we take in MS care.

Thank you very much

- Dr. Daniel Kantor, MD BSE
Medical Director
Neurologique

info@neurologique.org
www.neurologique.org

ECTRIMS is heating up

Real-time, real sessions, real answers.

I am answering this question during an immunomodulatory plenary session at ECTRIMS -- see my blogs at same time (www.neurologique.org --> Twitter).

I thought this would be valuable while it is still hot.

Question:

I was looking on the internet this morning trying to get some information about Florida when I came across this e-mail address.

I have had MS for about 8 years now and so far I have been blessed with not having too many issues.

Heat is one of my worst enemies. I am planning on going on a cruise in November and am worried about the heat/humidity in Florida.

Do you have any tips that may help me with dealing with these issues?

Thank you for the email.

Amswer:

Florida is hot and humid, but less so in November than August.

Heat sensitivity causes something called Uhthoff's phenomenon -- see:

http://www.medhelp.org/posts/Multiple-Sclerosis-MS/MS-Symptoms-and-being-sick/show/756505

The ways to deal with it are:

1. Try to minimize your direct sun exposure (this is good advice to prevent skin cancer, as well).
2. Drink plenty of cold water/fluids (much of the overheating occurs because of mild dehydration and a cold drink can help bring down your core body temperature.
3. Consider using a cooling device, such as a cooling device. Also, because of the high humidity, evaporative techniques (dipping a special vest or scarf in water) do not work -- so you need to use the ice-pack cooling vests. See the MSF (MS Foundation) and MSAA (MS Association of America) resources.
4. Talk to your doctor about a compounded medicine called 4-aminopyridine. Note that this is a compounded medication and not FDA approved yet as a pill.

If you do get overheated, then try to cool down your core body temperature by cooling areas that have a superficial blood supply (just like where you put perfume and where you put ice packs when someone has heat stroke).

Most likely, however, you will do well and enjoy your cruise!

- Dr. Daniel Kantor, MD BSE
Medical Director
Neurologique

info@neurologique.org
www.neurologique.org

In memoriam

On this September 11th, we remember those who dies and stand beside the families of those that died tragically.

- Dr. Daniel Kantor, MD BSE
Medical Director
Neurologique

info@neurologique.org
www.neurologique.org

Multimedia Sources (MS)

As I attend ECTRIMS and look for answers, the questions keep coming in:

Question:

What can you tell us about trials and developments with estriol? Like many other patients who inject their medication, I am eagerly awaiting an oral medication.

Thank you for your devotion to finding MS answers.

Answer:

As I am sure you are aware, there are many other medications in clinical trial development (orals, intravenous/IV and even some more injections under the skin).

Estriol is a pregnancy hormone secreted by the placenta and the rationale for its use is that woman have MS more than men and MS seems to be its best during pregnancy (I think only the second and third trimester) and worsens after delivery.

The question is whether these observations are going to translate into an effective and safe medication. Also, will estriol only be used in combination (just like Vitamin D is) with a standard MS drug or will it be good enough alone?

There is currently a large trial combining estriol with Copaxone (glatiramer acetate).

Question:

I have had RRMS since 1988. I have had a symptom of all-over itching, with no rash/hives, etc., for the past 10 yeas. Because it was periodic, it was then controlled by hydroxyzine, as needed.

Eighteen months ago, the itching increased in intensity and became a 24-hour symptom - made worse by humidity, heat, fatigue and stress.

I am currently on Singulair, Doxepin, Xyzal and Neurontin daily, with the hydroxyzine again taken as needed when all else fails.

I have talked to my neurologist, primary care doctor and dermatologist, but we have exhausted all antihistamines with little success. I am set to see an MS specialist in October, but my own research has shown me, among other things, the following:

1. Itching is usually a short-lived symptom;
2. It can signal the beginning stages of the more advance stages
of MS; and
3. Novantrone is the medication used at that time.

My question: Is the intensity of this symptom as I currently experience it that rare; and could this signal that I have become Secondary Progressive (I have not had a relapse in many years, but previous symptoms have increased in duration/intensity).

Thank you for any help you can give me.

Answer:

Other people report itching as an MS symptom -- it probably stems from sensory disturbances or from involvement of the autonomic nervous system (unlikely).

I think that before jumping to conclusions like SPMS and novantrone (mitoxantrone), it behooves you to see your new MS neurologist.

Not having a relapse for many years, could be an indication that your MS has changed to secondary progressive, or it could be a good sign that your MS is well controlled and then the symptoms you are having may just worsening for other reasons (such as core body temperature, etc.).

Your neurologist may consider the use of compounded 4-aminopyridine, but this would be an off-label use of the compound.

Then the power of the MS community was felt through the Multiple Sclerosis Patient Network (M*S*P*N) with this patient's response back:

Thank you so very much for replying to my question. I will definitely take your advice. If it's okay, I'll let you know the outcome after I see the specialist next month.

Please feel free to use my question on your blog. It is so hard to get information about itching - anyone with this problem who reads your advice will know they are not alone.

Again, thank you for your reply and detailed advice. You are the only doctor who has been able to give me any direction - I can't say what it means when someone with a chronic illness is finally given some hope for relief from such an annoying symptom.

As always, stem cells are a big question and we received several questions, such as this one:

Question:

Many MS patients are going to Costa Rica, Panama & Israel for autologous stem cell transplants.

Improvements are reported by numerous patients. .

What is your opinion of the efficacy, safety and value of these treatments? Also, do you believe the improvements will continue for these patients or revert back to their previous condition?

And, when do you see the US, Canada and the European countires offering

this treatment?

Answer:

The jury is still out on stem cells.

You probably remember all the excitement in the 1990s surrounding genetic engineering; since then there have been little advances in helping diseases.

Stem cell research is still in its infancy and in all of the protocols patients are first given very heavy duty chemotherapies/immunosuppresants, which contribute to most of the benefit in treating MS.

Stem cell transplantation is also a risky procedure and is especially dangerous in unregulated countries.

The question is going to be how we direct stem cells into the damaged areas.

- Dr. Daniel Kantor, MD BSE
Medical Director
Neurologique

info@neurologique.org
www.neurologique.org

Fingolimod: Risk taking with efficacy

Novartis symposium -- risk taking and confident.

Much of session focused on neurodegeration and not neuroinflammation.

Dr. Barkhof (yes, the “Barkhof criteria” person) reiterated the important neurodegenration markers:

1 . Brain volume/atrophy

2. T1 hypointensities (unfortunate name of “black holes”)

3. OCT

Ludwig Kappos reviewed Phase II and Phase III (TRANSFORMS) and future (now recruiting) 3-year INFORMS (primary progressive MS).

INFORMS looks at

a.. OCT

b. Brain volume

c. MTR

d. Evolution of black holes

Phase II and extension has sustained effect over 5 years and Phase III (TRANSFORMS) – well known data of 0.5 mg vs. 1.25 mg vs. Avonex (interferon beta-1A intramuscular weekly).

If this works for RRMS and PPMS, I wuld assume that it works for SPMS too.

- Dr. Daniel Kantor, MD BSE
Medical Director
Neurologique

info@neurologique.org
www.neurologique.org

LIVE from ECTRIMS

All this week I will be video blogging, text blogging and twittering from ECTRIMS (European Committee for Treatment and Research in MS) in Dusseldorf, Germany.

For the real-time video feeds, please visit www.neurologique.org or http://www.msworld.org/html/ectrims09.htm or http://www.youtube.com/results?search_query=ectrims+2009+kantor&search_type=&aq=f

In ECTRIMS, more than at American meetings, there are "satellite" programs, which are sponsored by pharmaceutical companies in an attempt to discuss a specific topic. An example would be a company that is developing an oral medication for MS, to sponsor one of these symposia.

MS Forum is an educational organization with educational grants from Bayer HealthCare Pharmaceuticals. The program was fairly non-product specific, except maybe for a heated debate concerning the role of neutralizing antibodies (Dr. Barry Arnason believes that neutralizing antibodies to beta interferon may actually be beneficial and could perhaps be developed into a treatment for MS, while Prof. Reinhard Hohlfeld disagrees and thinks that patients should be tested for NAbs).

Prof. Ludwig Kappos discussed the role of neuropsychological testing. He highlighted the need for testing for cognitive difficulties and he pointed out that fMRI (functional magnetic resonance imaging) studies show that MS patients recruit larger networks to compensate* and perform the same cognitive tasks as those without MS, but then if further cognitive decline occurs, less areas of the brain will be functioning.

This is further evidence why we need to develop more therapies that can delay, not only physical diosability, but cognitive dysfunction as well.

How many out there have been told "but you look so good?"

For the agenda from the MS Forum program, please visit:

http://docs.google.com/gview?a=v&q=cache:ruQ-IVZiGhcJ:allaroundexperience.com/Programme_MSForum_ECTRIMS2009.pdf+ms+forum+bayer+ectrims+2009&hl=en

* This over-recruitment of neural networks occurs in other neurological diagnoses as well.

- Dr. Daniel Kantor, MD BSE
Medical Director
Neurologique

info@neurologique.org
www.neurologique.org

Questions on the road

Progressive MS, back in the limelight.

At all medical/research meetings, neurologist clamor for the development of treatment for progressive MS -- this ECTRIMS (European Committee for Treatment and Research in MS) is no different.

On the way to Dusseldorf, Germany, I received the following question:

Question:

What treatment options are there for those of us who of progressive ms.....all the medications that are out there are for those people who have had events and I have never had one.....

Answer:

Unfortunately all of the currently FDA approved disease modifying medications work mostly in relapsing remitting MS (RRMS).

We often use chemotherapies in the treatment of progressive MS -- such as, mitoxantrone (novantrone), cyclophosphamide (cytoxan), etc.

More recently there have been trials with dirucotide (MBP8298), with unfortunately negative results.

There are ongoing trials with FTY720 (fingolimod) and many of us believe that rituximab (rituxan) works in progressive MS (despite the clinical trial) -- we will see what happens with ocrelizumab.

At Neurologique, we are working diligently on developing a medication for progressive MS; once clinical trials commence, we will be sure to announce this prominently.

The follow-up question was:

Question:

Are there any natural ways to help with progressive ms....I am taking 4000 IU of Vit D as my level is low and I take B12 shots every other week to maintain my levels close to 600.....are they are other suggestions to keeping this at bay.....many thanks.....Barb Sengstaken....I don't mind my email or name listed on your below listed question because perhaps people like me would like to chat on email unless you think that is not safe......

Answer:

t depends what you mean by "natural."

B12 levels of 600 are not that high, so you may want to consider with your doctor going higher and there may be a reason why despite the injections, your levels are still not very high.

Some patients opt to take LDN (low dose naltrexone), but this is hadly "natural."

See:

http://www.youtube.com/watch?v=Kz52KK5IhOc

Another great question was raised by a highly trained patient:

Question:

Recently, Dr. Galipeaux from McGill University published a paper that astounded many of us. From their results, it would appear that there might be a cure for MS sometime in the future. Has the action of a fusion protein for humans like the one they made for mice been constructed yet, and if so, what is the plan for clinical trials to test its efficacy?

I realize that the possibility of immune reaction against such a protein is possible, but if the outcome is anything like what happened in the mice, MS could actually be cured in our lifetime.

Thanks for your help with this issue.

Answer:

The mouse research suggests that by mixing B-cells (a type of immune cells) with a combination of two proteins (GIFT15) can then be infused back into the mouse to cause immunosuppression.

While this sounds exciting, we have to be careful in trying to manipulate the immune system (an example was the attempt to use interferon gamma to treat MS, when we now know that it worsens MS). The other issue is that we cannot always generalize our findings in mouse models to human beings with MS.

Also, this treatment is a strong immunosuppressant, but it does not directly reverse MS (it just halts the body from further attacking itself) -- much like alemtuzumab (campath) and high dose cyclophosphamide (HiCy).

Getting back to daily reality, I received the following question:

Question:

Why are my MS symptoms so much worse during the time if the month??

Answer:

During your period, your core body temperature rises, which leads to an uncovering of older MS symptoms.

This is called Uhthoff's phenomenon -- see:

http://www.medhelp.org/posts/Multiple-Sclerosis-MS/MS-Symptoms-and-being-sick/show/756505

- Dr. Daniel Kantor, MD BSE
Medical Director
Neurologique

info@neurologique.org
www.neurologique.org