FIRST ASSESSMENT OF THE ANTI-ALPHA-SYNUCLEIN PRX002 FOR PARKINSON'S DISEASE

30th November 2016 - New research

Alpha-synuclein can accumulate under certain conditions, primarily in Parkinson's Disease, dementia with Lewy bodies, and multiple system atrophy, but also in Alzheimer's Disease and neuroaxonal dystrophies. Small amounts of alpha-synuclein can also occur in individuals who do not have neurological disorders. The cytological effects of Parkinson's Disease can include the formation of hydrogen peroxide (because of the breakdown of superoxide anion), and also the accumulation of iron. Alpha-synuclein expression is regulated by iron, and hydrogen peroxide plays a dominant role in the aggregation of alpha-synuclein. It inhibits tyrosine 3-monooxygenase, which is the enzyme needed to form dopamine, whose deficiency causes Parkinson's Disease. 

PRX002 is an antibody that targets alpha-synuclein, which has been shown in preclinical animal studies to reduce alpha- synuclein pathology and to protect against cognitive and motor deteriorations and progressive neurodegeneration. This first-in- human, phase 1 clinical trial assessed the impact of PRX002 administered to healthy participants in 5 doses (either 0.3, 1, 3, 10, or 30mg/kg) or a placebo.

PRX002 demonstrated favourable safety, tolerability, and pharmacokinetic profiles at all doses tested, with no immunogenicity. No serious adverse events, discontinuations as a result of adverse events, or dose-limiting toxicities were reported. A significant dose-dependent reduction in free serum alpha-synuclein was apparent an hour after PRX002 administration.

Reference : Movement Disorders [2016] Nov 25 [Epub ahead of print] (D.B.Schenk, M.Koller, D.K.Ness, S.G.Griffith, M.Grundman, W.Zago, J.Soto, G.Atiee, S.Ostrowitzki, G.G.Kinney) 

Complete abstract : http://www.ncbi.nlm.nih.gov/pubmed/27812535

http://www.viartis.net/parkinsons.disease/news/161130.pdf