Riluzole completed Phase I for PPMS

A board to discuss future MS therapies in early stage (Phase I or II) trials.

Riluzole completed Phase I for PPMS

Postby dignan » Tue Sep 06, 2005 7:59 am

The Accelerated Cure project mentioned this small Phase I trial in their news section today. Riluzole is a drug for ALS. It's always good news when they test a drug for PPMS.



Glutamate inhibition in MS: the neuroprotective properties of riluzole

J Neurol Sci. 2005 Jun 15;233(1-2):113-5. Epub 2005 Apr 20.

Killestein J, Kalkers NF, Polman CH.
Department of Neurology, VU Medical Centre, P.O. Box 7057, 1007 MB, Amsterdam, The Netherlands. J.Killestein@vumc.nl

In addition to demyelination and damage to oligodendrocytes, axonal injury and neuronal cell death are dominating histopathological characteristics of multiple sclerosis (MS). Still little is known about the cause of the damage. Extracellular accumulation of glutamate contributes to excitotoxic injury of neurons and glial cells, suggesting that the maintenance of subtoxic extracellular glutamate levels may be crucial.

Riluzole is a neuroprotective agent that inhibits the release of glutamate from nerve terminals and modulates glutamate, i.e., kainate and NMDA receptors. It inhibits excitotoxic injury in several experimental models of neurodegenerative disease.

We performed a small run-in versus treatment MR-monitored pilot study in 16 primary progressive MS patients. The results suggest that riluzole reduces the rate of cervical cord atrophy and the development of T1 hypointense lesions on magnetic resonance imaging in primary progressive MS. The rate of brain atrophy was only slightly decreased. The results indicate an effect on mechanisms involving lesion evolution and axonal loss, but no clear effect on new lesion formation.

However, the data suffer from several limitations and must be confirmed in future trials.


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Postby bromley » Tue Sep 06, 2005 8:35 am

Dignan,

I also saw this research paper. The study size was small and it's strange that they did not include some participants with Secondary Progressive MS to see if there was any difference between the two groups.

If there is one word I would eliminate from the English language it is 'atrophy'.

The classic line from this paper is 'Still little is known about the cause of the damage'. Until someone gets to the bottom of this then most of these trials are going to be shots in the dark.

OddDuck was always making references to glutamate. It seems to be involved somehow but not sure if it causes the damage or is a response to something else?

I'm hoping that the ACTRIMS / ECTRIMs conference, which is taking place in Greece at the end of the month, will showcase some positive results from some of the drugs currently on trial and maybe some better understanding of this disease. At least the researchers now acknowledge that more is going on than just demyelination!

Keep up you postings - just one of these days one of these trial drugs might actually deliver!

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