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Based on Bromley's post today, Neurocrine's Phase II treatment has failed and is being yanked from the list. Crap, that's two failures in the last couple of weeks. Hopefully there's good news in the offing.

a little more detail on the Neurocrine treatment:

"Wendell Wierenga, Executive Vice President of Research and Development for Neurocrine Biosciences, said, "Our Phase II study in multiple sclerosis patients showed APL-MS to have an excellent safety profile, but unfortunately the study did not achieve statistical significance in efficacy in the 157 patients tested over the 9-month treatment period."

Link

So maybe this might be some good news. An article posted on the BBC yesterday (8/3) about a trial by PharamFrontiers. It doesnt state the name of the drung on trial but it must be Toxavin (44 in dignan's list).

BBC http://news.bbc.co.uk/nolpda/ukfs_news/ ... 787430.stm

Toxavin http://www.pharmafrontiers.net/toxavintrials.php

It was about Tovaxin. The following is from the Guardian (a UK paper).

Ian

http://c.moreover.com/click/here.pl?j482821732&w=464753

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nutrovitasub just posted an ad for a website, is it wrong to ask you, Arron, to delete this post?

Since BioMS is starting trials for RRMS, I'll add their drug to the list again. I assume that this trial will be phase II. If anyone knows more, feel free to share.

Per Bromley's request, adding Stanford University's "DNA vaccination" treatment to Phase II.

Based on a post by Bromley, I moved NNZ-2566 from Neuren to phase I from pre-clinical.

Based on some poking around, I made a couple of changes to the list. I moved cyclophosphamide from phase III to phase II based on this info:
http://www.clinicaltrials.gov/ct/show/N ... 5?order=30

I also put in a phase III study of mycophenolate mofetil plus Avonex based on this info:
http://www.clinicaltrials.gov/ct/show/N ... 1?order=53

For the record, there are now 140 substances on the list. There are 145 entries, with 5 that are in twice (either "approved" plus ongoing trials or "off-label" plus ongoing trials).

Having finished reading Curing MS by Howard L. Weiner, M.D. I found the following lines that might be useful to those who manage the pipeline:

Basic and clinical research in MS is moving at a rapid pace. If the reader is interested in the cutting edge of what is happening in MS before it appears in the next edition of Curing MS, please visit our MS center website (www.mscenter.net). At the end of each year, I write a review of progress under the heading "What's new in MS research and clinical trials."

Thanks for the tip. One thing I found interesting was this phase II study due to finish in 2006.



Interferon Tau (Tauferon): This is an oral interferon preparation from sheep which has been shown to work in the animal models of MS and which is being tested in a small Phase II MRI-based trial in relapsing remitting MS at our center and in other centers across the country. Results are expected in 2006. If positive results are obtained, further trials of this oral interferon will be undertaken.

Here's a new one. Not quite sure where to put it since it is primarily being tested for cancer, but they say it will be investigated for MS as well...I think I'll say phase I until they actually announce a phase II trial.



SGN-30 (Seattle genetics).

Curr Opin Mol Ther. 2006 Apr;8(2):164-72.
Schnell R, Borchmann P.
Department of Internal Medicine I, University of Cologne, Joseph-Stelzmann-Strasse 9, D-50924 Cologne, Germany. roland.schnell@uni-koeln.de

Seattle Genetics is developing SGN-30, an intravenously administered recombinant anti-CD30 monoclonal antibody for the potential treatment of Hodgkin's disease, certain non-Hodgkin's lymphomas, specific leukemia, and immunological diseases such as multiple sclerosis and systemic lupus erythematosus. Phase II trials in patients with Hodgkin's disease, anaplastic large cell lymphoma, and cutaneous lymphoma have been conducted in the U.S. and Europe.

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http://www.seattlegenetics.com/clinical/30trials.htm

Another new one (Calpeptin) in pre-clinical tests. It seems to be targeted at neuroprotection.



Calpeptin provides functional neuroprotection to rat retinal ganglion cells following Ca(2+) influx.

Brain Res. 2006 Apr 4
Das A, Garner DP, Del Re AM, Woodward JJ, Kumar DM, Agarwal N, Banik NL, Ray SK.
Department of Neurosciences, Medical University of South Carolina (MUSC), 96 Jonathan Lucas Street, Suite 323K, P.O. Box 250606, Charleston, SC 29425, USA.

Apoptosis of retinal ganglion cells (RGCs) impairs vision in glaucoma patients. RGCs are also degenerated in multiple sclerosis (MS), resulting in loss of visual perception in MS patients. We examined the involvement of calpain and caspase cascades in apoptosis of the rat retinal ganglion cell line RGC-5 following 24 h of exposure to 250 nM ionomycin (IMN) or 300 units/ml interferon-gamma (IFN-gamma) and then evaluated functional neuroprotection with 2 muM calpeptin (CP, a calpain-specific inhibitor). Morphological and biochemical features of apoptosis were detected in RGC-5 cells following exposure to IMN or IFN-gamma. Fura-2 assay determined significant increases in intracellular free [Ca(2+)] following exposure to IMN or IFN-gamma.

Pretreatment with CP for 1 h prevented Ca(2+) influx, proteolytic activities, and apoptosis in RGC-5 cells. Western blot analyses showed an increase in activities of calpain and caspase-12, upregulation of Bax:Bcl-2 ratio, release of cytochrome c from mitochondria, and increase in caspase-9 and caspase-3 activities during apoptosis. Increased caspase-3 activity was also confirmed by a colorimetric assay. Activation of caspase-8 and cleavage of Bid to tBid in RGC-5 cells following exposure to IFN-gamma indicated co-operation between extrinsic and intrinsic pathways of apoptosis. Patch-clamp recordings showed that pretreatment with CP attenuated apoptosis and maintained normal whole-cell membrane potential, indicating functional neuroprotection.

Taken together, our results demonstrated that Ca(2+) overload could be responsible for activation of calpain and caspase cascades leading to apoptotic death of RGC-5 cells and CP provided functional neuroprotection.

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