Pridopidine

Pridopidine (formerly Huntexil, ACR16, also ASP2314) is an orally bioavailable small molecule investigational drug candidate. It is a highly selective Sigma-1 Receptor (S1R) agonist. The S1R regulates key cellular processes relevant to neurodegenerative diseases, such as calcium homeostasis, cytoskeleton dynamics, restoring mitochondrial health and neurotrophic factor release. S1R is implicated in cellular differentiation, neuroplasticity, neuroprotection, and cognitive functioning of the brain.
Pridopidine positively influences S1R regulated pathways across neurodegenerative and neurodevelopmental indications, including protection against axonal and neuronal injury, restoring spine impairments, enhancing BDNF secretion and restoring mitochondrial function.
Priodopine was previously thought to be a dopamine D2 receptor (D2R) antagonist but this was discovered to be incorrect.
Pridopidine is in late-stage development by Prilenia Therapeutics. Previously it was owned by Teva Pharmaceutical Industries who acquired the rights to the product from its original developer NeuroSearch in 2012.
Pridopidine is the first drug to show statistically significant effect on maintenance of functional capacity in Huntington's Disease (HD), as measured by Total Functional Capacity (TFC). This effect was most prominent in early HD patients.
While Pridopidine at low doses affects S1R, at higher doses it interacts with other targets including dopamine D3, adrenergic α2C and serotoninergic 5-HT1A, which are established therapeutic targets for Parkinson's Disease Levodopa Induced Dyskinesia (PD-LID). This is the likely mechanism for the clear effect seen in the “gold standard” non-human primate model for PD-LID – the MPTP-Lesioned Macaques. This model is considered highly translatable to success in phase 2 clinical trials.
Pridopidine is currently in phase 2 clinical development for PD-LID, and was recently chosen to participate in a novel platform trial for amyotrophic lateral sclerosis (ALS) by the Sean M. Healey & AMG Center for ALS at Massachusetts General Hospital.