Just a note that the ECTRIMS 2006 abstracts will be released on Wednesday. (ECTRIMS = European Committee for Treatment and Research in Multiple Sclerosis)

My primary interest is in research into new therapies, since basic research is further removed in time from effectively helping us.

A batch of research on FTY720, or fingolimod, will be released. As most of you from Braintalk may know, this drug is derived from a fungus used in traditional Chinese medicine. Sphingosine 1-phosphate receptors control the egress of T-cells from lymph nodes. FTY720 acts on these receptors with the result that T-cells are sequestered in the lymph nodes. (If they're in the lymph nodes, they're not in the brain attacking myelin or axons.)

The drug is oral, and appears to be about as effective as Tysabri in reducing relapse rate and the appearance of enhancing lesions. I don't believe we have seen results reported from the phase II trial on reduction in disability progression (we might hope it is somewhat more effective than Tysabri). Reduction in progression was not a primary outcome of the phase II trial.

The phase III trial of the drug is recruiting over 2,000 patients, and is testing both the lower dose (1.25 mg) used in the phase II trial, as well as an even lower dose (0.5 mg). The 1.25 mg dose was as effective as the higher 5 mg dose used in the phase II trial.

Although the drug has proven safe so far, because of the mechanism of action, some of the same concerns surround the drug as Tysabri. (If the T-cells are stuck in the lymph nodes, and a virus invades the central nervous system, will the immune system be able to effectively fight the virus?)

BG00012 is an oral immunomodulatory drug which has proven effective in psoriasis. Last January we learned that in a phase II trial in MS, the drug had met its primary endpoints, although I haven't seen how effective the drug proved. The phase II trial had four groups roughly divided evenly between three different doses and a placebo, lasted two years and had 257 patients.

I suspect the numbers will be released at the conference, but Biogen tells us that the drug achieved a statistically significant result on the primary outcome (reduction of enhancing lesions) as well as secondary outcomes such as reduction in T1 hypointense lesions.

The conference has a session (multiple papers) devoted to IVIg.

Of course a substantial number of papers will be presented on the interferons, Copaxone, Novantrone, and combinations of these with each other and with steroids and Imuran. A double-blinded study comparing doses of Copaxone will be presented.

A session is being devoted to cannibinoids, considering their potential both as symptomatic therapy (e.g. for spasticity) and more importantly, for their potential as disease-modifying therapy through neuroprotection.

As many of you know, current drugs seem to effectively reduce inflammation, and yet the drugs appear much less effective in reducing neurodegeneration and subsequent disability. We need drugs which protect the axons. THC may be such a drug.

Another such drug is Lamotrigine (trade name Lamictal). This drug is used to treat bipolar disorder, epilepsy, and migraines. It appears to work by inhibiting the release of glutamate in the central nervous system, by targetting overactive voltage-gated sodium channels.

The drug appears similar (in this way) to riluzole, which has been proven modestly effective in ALS. Glutamate (excitotoxicity) has long thought to promote neurodegeneration.

Mark

Thanks Mark. I'm going to go have a look at what's there. Sounds like there's actually some interesting things coming up. I don't even know what psoriasis is, will have to look that up and see how a drug for that could help with MS.

Wouldn't that be the kicker if components of marijuana turned out to be our silver bullet?

Hi Mark -- good to see you!

I tried a sample pak of Lamictal and made it to the fifth week. Had to stop then due to horrible headaches, sleeplessness (more than usual). Of course that's the one that can possibly cause a rash which could prove deadly if it gets in the mucous membranes.

Have you heard anything regarding the Tovaxin trial? The results from previous trials sounded pretty encouraging for those of us with progressive types of ms. We really need something along those lines that will repair the damage all ready done!!

I'll be looking forward to your informative messages! That's one reason Braintalk was a favorite. Take care.

Hi Judy,

I have long been excited by the concept of Tovaxin. Dr. Jinwu Zhang -- still at Baylor I think -- has been researching this therapy since at least the early 90s. The initial formulation was monovalent -- which meant that it had the effect of only deactivating one type autoreactive T-cell primed for one particular protein. The first trial results with this formulation were ok but not spectacular.

The researchers then created a trivalent formulation which deactivated three types of autoreactive T-cells primed for three types of proteins. Given what we now know about MS, this made much more sense, and the trial results from this formulation looked great.

The trial is a phase IIb trial so even if successful, the company will still need to conduct a phase III trial, so unfortunately approval of the therapy seems years away -- the company optimistically says "2010". Dr. Edward Fox is the lead clinician on the trial, and certainly he's a known name in MS research.

At one of the other forums, some hubbub was created (I believe) by the fact that someone who was using Tovaxin successfully, and touting the therapy on the internet, had a financial interest in the therapy (or at least his parents did).

But again, Dr. Fox is for real, the company (Opexa) is for real (and just raised $23 million), and the trial is for real. (The company just changed their name from PharmaFrontiers back to Opexa.) The government trial page for Tovaxin lists all the sites participating in the trial, as well as exclusion criteria. Unfortunately the trial seems to be excluding anyone with progressive forms of MS.

Re: Lamictal, sorry you had problems. The potentially fatal Stevens-Johnson rash is the big worry. Another problem is interaction with other drugs -- as one person put it "Lamictal interacts with drugs you don't even take".

Wannabe: Yes would be interesting if MS neuroprotection became the reason the US government was forced to admit the utility of medical marijuana.

Mark

I, like so many others, have been at a great loss without the research tool this forum provided. I am still taking the acetyl-L-carnitine and Lipoic acid pills and have stopped ritalin. My energy levels were outstanding during the whole summer's farming season.

I remember the reports from Teva about success with a higher dose of copaxone. It seemed like quite a hopeful study, reporting very quick improvments for test subjects.

Just last week, in response to a violent flu like illness that my husband and I got, I had a first incident of being suddenly unable to move a leg. I kept hinking:"move leg" but nothing happened. Well, that was unsettling. On the floor for 5 hours and unable to get up at all. So, right leg was also involved as well as neck. Then, it eased and, as days went by, eased some more. I can now walk again--just not as well as before.

So, I am looking for the research on 4-AP that showed it helpful in improving leg strength. The novantrone discussion is at the forefront again. I should have printed off all the research articles you post!

The IVIg research really interests me. For the last 2 months we had been reducing the amount I get but now we are increasing it again. I think I miscalculated how well I was!

I am so grateful to have this connection back.
Linda~~from Western Massachusetts

(5 years on IVIg. 70g every other week. copaxone.)

Thank you for the information Mark. This does look pretty promising.

I have missed your research posts since BT was down. Nice to be back again

hello Mark, thanks for the info. i'm glad your here.
mark from michigan

Thanks for your answer Mark. I knew I could count on you!! Was the guy involved with the Tovaxin the one with red hair? That's the site I had found. Hope they speed up those trials a little. I'm not a 'spring chicken' anymore and the clock keeps ticking!!

I think it was Lazarus who mentioned being "on the floor for five hours"???? My 'brain' has forgotten already. Anyway, maybe you should get a Life Alert thingy. The commercials always made me laugh -- until it actually happened. Now I wear one as a bracelet around the house and do feel safer.

Have a nice day everyone.

Mark -

how are you accessing any information from ECTRIMS?

When I click on any of the modules, it says "no text available".

How are you bringing up the abstracts?

Hi wannabe,

Some of the abstracts are available, others are not (and those say "Text not available"). I think you must be trying to access unavailable ones. For example do a search for "fingolimod" there, and click on one of the abstracts I posted earlier, and I think the abstract will pop up.

Mark