Novel drug slows progression of Lou Gehrig’s disease


London: A novel drug dexpramipexole may help slow symptom progression in the neurodegenerative disease amyotrophic lateral sclerosis (ALS), a new study has suggested.

It is believed that the drug, dexpramipexole, work by preventing dysfunction of mitochondria – the subcellular structures that provide most of a cell’s energy.


Initially developed by Knopp Biosciences of Pittsburgh, dexpramipexole appears to protect neurons from mitochondrial dysfunction.

Results of the first stage showed that receiving dexpramipexole appeared to slow the progression of symptoms measured both by the ALS Functional Rating Scale and by pulmonary capacity.

The protective effect was greatest in the 300 mg group – in whom symptom progression was approximately 30 percent slower than in the placebo group – and little effect was seen in those receiving 50 mg.

The second stage had similar results, with slower disease progression and a reduced risk of death in participants receiving the higher dosage.

http://zeenews.india.com/news/health...ase_14656.html

Results of the study will be published online in Nature Medicine.

Dexpramipexole, the R(+) enantiomer of pramipexole, for the potential treatment of amyotrophic lateral sclerosis.
Cheah BC, Kiernan MC.


Abstract
Dexpramipexole (KNS-760704), the R(+) enantiomer of pramipexole, is under development by Knopp Neurosciences and Biogen Idec as a potential neuroprotective therapy for amyotrophic lateral sclerosis (ALS), a universally fatal neurodegenerative disease. Pramipexole, exclusively the S(-) enantiomer, is a non-ergot dopaminergic autoreceptor agonist that is currently marketed for use in the treatment of Parkinson's disease and restless legs syndrome. Pramipexole has been proposed to exert a broad spectrum of neuroprotective properties, primarily through antioxidant effects, inhibiting apoptotic enzymes and preserving mitochondrial structure and activity. More recent work has suggested that pramipexole possesses anti-excitotoxic properties, raising the possibility of beneficial effects in patients with ALS. However, pramipexole has high intrinsic dopaminergic receptor activity and, consequently, dose-limiting side effects, including orthostatic hypotension and hallucination, are frequent. Dexpramipexole exhibits significantly lower affinity for dopaminergic receptors, thereby making it unlikely to be associated with dopaminergic side effects. In clinical trials to date, dexpramipexole has been safe and well tolerated at doses up to 67-fold higher than the maximum recommended daily dose of pramipexole in patients with Parkinson's disease, and has demonstrated signs of neuroprotective benefit. This report summarizes the chemical and pharmacological properties of dexpramipexole and describes the potential utility of the drug in the pharmaceutical development pipeline.

PMID: 21154151 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/pubmed/21154151