Amyotrophic lateral sclerosis and the clinical potential of dexpramipexole

myotrophic lateral sclerosis and the clinical potential of dexpramipexole Review (1697) Total Article Views Authors: Corcia P, Gordon PH Published Date August 2012 Volume 2012:8 Pages 359 - 366 DOI: http://dx.doi.org/10.2147/TCRM.S21981 Received: 20 July 2012 Accepted: 01 August 2012 Published: 27 August 2012 Philippe Corcia,1 Paul H Gordon2 1Centre SLA, CHRU de Tours, Tours, France; UMR INSERM U930, Université Fran ois Rabelais de Tours (PC), Tours, France; 2AP-HP, H pital de la Pitié-Salpêtrière, Département des Maladies du Système Nerveux (PHG), Paris, France Abstract: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder that leads to progressive weakness from loss of motor neurons and death on average in less than 3 years after symptom onset. No clear causes have been found and just one medication, riluzole, extends survival. Researchers have identified some of the cellular processes that occur after disease onset, including mitochondrial dysfunction, protein aggregation, oxidative stress, excitotoxicity, inflammation, and apoptosis. Mitochondrial disease may be a primary event in neurodegeneration or occur secondary to other cellular processes, and may itself contribute to oxidative stress, excitotoxicity, and apoptosis. Clinical trials currently aim to slow disease progression by testing drugs that impact one or more of these pathways. While every agent tested in the 18 years after the approval of riluzole has been ineffective, basic and clinical research methods in ALS have become dramatically more sophisticated. Dexpramipexole (RPPX), the R(+) enantiomer of pramiprexole, which is approved for symptomatic treatment of Parkinson disease, carries perhaps the currently largest body of pre- and early clinical data that support testing in ALS. The neuroprotective properties of RPPX in various models of neurodegeneration, including the ALS murine model, may be produced through protective actions on mitochondria. Early phase trials in human ALS suggest that the drug can be taken safely by patients in doses that provide neuroprotection in preclinical models. A Phase III trial to test the efficacy of RPPX in ALS is underway.