Dual gene-chaperone therapy for efficacious treatment of neurodegenerative disease

This technology is a combination therapy for neurodegenerative diseases that combines oral delivery of a pharmaceutical chaperon molecule with viral vector delivery of gene therapy.

Unmet Need: Efficacious treatment for neurodegeneration targeting the endosomal system

Many neurodegenerative diseases have no cure, and available treatment options are limited and ineffective. Endosomal trafficking defects have been implicated in neurodegenerative diseases like Alzheimer’s Disease, Parkinson’s Disease, neuronal ceroid lipofuscinosis, and transmissible spongiform encephalopathies. However, efforts to develop treatment options targeting this pathway have shown limited success.

The Technology: Viral vector-mediated gene therapy combined with chaperone delivery for increased efficacy

This technology is a combination therapy for neurodegenerative diseases comprising both an orally-delivered pharmacological chaperone and a viral vector-delivered gene therapy. This approach utilizes two separate strategies to regulate retromer function and repair defects in endosomal trafficking by increasing levels of VPS35. As such, this technology has the potential to treat root causes of neurodegenerative disorders currently considered incurable.

Applications:

• Therapeutic for Alzheimer’s and Parkinson’s disease
• Therapeutic for neuronal ceroid lipofuscinosis
• Therapeutic for transmissible spongiform encephalopathies (prion diseases)
• Research tool for endosome trafficking dysfunction
• Research tool for retromer function

Advantages:

• Addresses root causes of neurodegenerative disorders
• Bypasses cell responses that may limit traditional viral vector-mediated gene therapy
• Acts locally in the brain, preventing peripheral undesirable effects

Lead Inventor:

Scott A. Small, M.D.

Patent Information:

Patent Pending (WO/2021/163681)

Related Publications:

• Berman DE, Ringe D, Petsko GA, Small SA. “The Use of Pharmacological Retromer Chaperones in Alzheimer’s Disease and other Endosomal-related Disorders.” Neurotherapeutics. 2015 Jan; 12(1): pp. 12-8.

• Vagnozzi AN, Li JG, Chiu J, Razmpour R, Warfield R, Ramirez SH, Praticò D. “VPS35 regulates tau phosphorylation and neuropathology in tauopathy.” Mol Psychiatry. 2019 Jul.

• Mecozzi VJ, Berman DE, Simoes S, Vetanovetz C, Awal MR, Patel VM, Schneider RT, Petsko GA, Ringe D, Small SA. “Pharmacological chaperones stabilize retromer to limit APP processing.” Nat Chem Biol. 2014 Jun; 10(6): pp. 443-9

Tech Ventures Reference:

• IR CU20246, CU21196

• Licensing Contact: Jerry Kokoshka