Latest articles provide novel insights into the mechanisms driving pridopidine neuroprotective effects

Prilenia Therapeutics B.V., a clinical stage biotech company focused on developing novel treatments for neurodegenerative and neurodevelopmental disorders, today announces the publication of three peer-reviewed journal articles, highlighting key aspects of the mechanism of action of its lead asset, pridopidine, and the importance of S1R activation as a mechanism to attenuate biological features of neurodegenerative diseases.

S1R is a protein highly expressed in the brain where it regulates several cellular mechanisms common to neurodegenerative diseases. Activation of the S1R improves energy production, reduces cellular stress, enhances clearance of toxic proteins and mitigates inflammation, thus supporting the continued function and survival of neurons.

These latest publications are the result of long-term collaborations with researchers from leading institutions across the globe and provide novel insights into the mechanisms driving pridopidine neuroprotective effects.

Highlights from the published articles include the following:

1.The Sigma-1 Receptor Mediates Pridopidine Rescue of Mitochondrial Function in Huntington Disease Models - Naia et al., Neurotherapeutics, 2021

* This article describes how pridopidine enhances mitochondrial functions by activation of the S1R, contributing to its neuroprotective effects and supporting its therapeutic potential in HD

2.Pridopidine reduces mutant huntingtin-induced endoplasmic reticulum stress by modulation of the Sigma-1 receptor - Shenkman et al., Journal of Neurochemistry, 2021

* This article demonstrates the effect of pridopidine on reducing mutant HTT-induced ER stress via activation of the S1R, providing additional evidence of its therapeutic potential as a selective and potent S1R agonist

3.Sigma-1 Receptor (S1R) Interaction with Cholesterol: Mechanisms of S1R Activation and Its Role in Neurodegenerative Diseases - Zhemkov et al., International Journal of Molecular Sciences, 2021

* This review article investigates the biological interactions between the S1R and cholesterol and looks into the therapeutic benefit of pridopidine as a selective and potent S1R agonist in neurodegenerative diseases.

Pridopidine is a first-in-class small molecule in clinical development for the treatment of HD and Amyotrophic Lateral Sclerosis (ALS). It is a highly selective and potent S1R agonist in clinical development for both indications. Pridopidine demonstrates neuroprotective effects in preclinical models of HD, ALS and other neurodegenerative diseases.

These new insights on pridopidine and how it affects S1R continues to advance our knowledge on its mechanism of action, which supports the development of this drug for HD and ALS."

Michael R. Hayden, MD, PhD, CEO, Prilenia

Hayden is a world-renowned expert in Huntington's Disease research

Pridopidine is a safe and well tolerated orally administered drug currently being assessed in a Global Phase 3 study (PROOF-HD), evaluating the effect of pridopidine 45 mg bid on Total Functional Capacity (TFC) in patients with early-stage HD. The study is being conducted in collaboration with the Huntington Study Group (HSG). Pridopidine is also being assessed in the first platform trial for ALS in collaboration with the Healey Center for ALS at Mass General Hospital.

Source:
Journal reference:

Naia, L., et al. (2021) The Sigma-1 Receptor Mediates Pridopidine Rescue of Mitochondrial Function in Huntington Disease Models. Neurotherapeutics. doi.org/10.1007/s13311-021-01022-9.

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