New pridopidine’s neuroprotective properties in Huntington’s Disease models

• Newly published papers further elucidate the mechanisms underlying pridopidine’s neuroprotective properties through activation of the Sigma-1 Receptor (S1R).
• Pridopidine enhances mitochondrial function and reduces mHTT-induced ER stress, which are impaired in HD, mediated by the S1R.
• Three new peer-reviewed publications highlight pridopidine’s therapeutic potential and provide data supporting the role of the S1R in neurodegenerative diseases.

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.

Michael R. Hayden, MD, PhD, CEO of Prilenia and world-renowned expert in Huntington’s Disease research, commented:

” 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.”

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.