Novel als therapy shows promise in phase ii

Access through your institution Buy or subscribe Despite recent advances in the genetics of ALS, the mechanisms underlying motor neuron degeneration are not fully understood. However,

accumulating evidence suggests that mitochondrial dysfunction may have a key role in motor neuron death. The benzothiazole dexpramipexole is being investigated as a potential ALS therapy as

it exerts broad neuroprotective properties involving antioxidant effects, inhibition of apoptotic enzymes and preservation of mitochondrial structure and activity. It is the _R_(+)

enantiomer of the dopaminergic autoreceptor agonist pramipexole, which is currently used to treat Parkinson's disease. Importantly, dexpramipexole has significantly lower affinity for

dopaminergic receptors than pramipexole, making it unlikely to be associated with dopaminergic side effects. The Phase II trial of dexpramipexole was uniquely designed in that the same

patients were randomized twice, creating two separate, double-blind studies. In part 1, 102 patients with ALS were randomized to receive daily divided oral doses of 50 mg, 150 mg or 300 mg

of dexpramipexole or placebo for 12 weeks. 92 of these patients continued to part 2, and after a 4-week placebo washout period, they were re-randomized to receive daily divided doses of

either 50 mg or 300 mg of dexpramipexole for 24 weeks. This is a preview of subscription content, access via your institution ACCESS OPTIONS Access through your institution Subscribe to this

journal Receive 12 print issues and online access $209.00 per year only $17.42 per issue Learn more Buy this article * Purchase on SpringerLink * Instant access to full article PDF Buy now

Prices may be subject to local taxes which are calculated during checkout ADDITIONAL ACCESS OPTIONS: * Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer

support ORIGINAL RESEARCH PAPER * Cudkowicz, M. et al. The effects of dexpramipexole (KNS-760704) in individuals with amyotrophic lateral sclerosis. _Nature Med._ 17, 1652–1656 (2011)

Article  CAS  Google Scholar  Download references Authors * Sarah Crunkhorn View author publications You can also search for this author inPubMed Google Scholar RIGHTS AND PERMISSIONS

Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Crunkhorn, S. Novel ALS therapy shows promise in Phase II. _Nat Rev Drug Discov_ 11, 22–23 (2012).

https://doi.org/10.1038/nrd3634 Download citation * Published: 16 December 2011 * Issue Date: January 2012 * DOI: https://doi.org/10.1038/nrd3634 SHARE THIS ARTICLE Anyone you share the

following link with will be able to read this content: Get shareable link Sorry, a shareable link is not currently available for this article. Copy to clipboard Provided by the Springer

Nature SharedIt content-sharing initiative