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