Restoring synaptic function to prevent and treat neurodegenerative diseases

This technology provides a pharmacological approach for increasing the levels of a E3 ubiquitin protein ligase in neurons to treat synaptic dysfunction and loss in neurodegenerative diseases, as Alzheimer’s disease (AD).

Unmet Need: Effective treatment of synaptic dysfunction in neurodegenerative disorders

Currently, the treatment of Alzheimer’s Disease (AD) and many other related neurodegenerative disorders are limited to temporarily alleviating the symptoms. While AD research has focused on the build-up of amyloid-β, this approach has not yet led to the development of a successful therapeutic that could halt or reverse the progression of neuronal degeneration. There is a clear need for disease-modifying therapeutics that target the underlying mechanisms of synaptic dysfunction to prevent neurodegeneration in AD and related disorders.

The Technology: Modulation of E3 ubiquitin protein ligase levels for restoring synaptic function

This technology identifies ubiquitin protein ligase E3A (UBE3A), an enzyme that plays a key role in synaptic function, as a therapeutic target for the treatment of AD, Parkinson’s disease, Huntington’s disease, and epilepsy. Compounds that can increase the levels of UBE3A in the brain, like a topoisomerase type I inhibitor or an UBE3A carrier agent, are described and can be used as therapeutics for treating synaptic dysfunction. As such, this technology provides a disease-modifying therapy for AD and other neurodegenerative diseases that are characterized by synaptic dysfunction.

This technology has been validated in mouse models of AD.

Applications:

• Treatment for AD, Parkinson’s disease, Huntington’s disease, and epilepsy
• Prevention of neurodegeneration
• Diagnostic marker and therapeutic for diseases characterized by synaptic dysfunction
• Research tool for understanding synaptic function and neurodegeneration
• Platform for screening ubiquitin ligase modulators

Advantages:

• Disease modifying therapy for AD, Parkinson’s disease, Huntington’s disease, and epilepsy
• Rescues synaptic function
• May prevent synaptic loss and neurodegeneration
• Uses FDA-approved drugs

Lead Inventor:

Roger Lefort, Ph.D.

Patent Information:

Patent Pending (US20200138921)

Related Publications:

• Olabarria M, Pasini S, Corona C, Robador P, Song C, Patel H, Lefort R. “Dysfunction of the ubiquitin ligase E3A Ube3A/E6-AP contributes to synaptic pathology in Alzheimer’s disease” Commun Biol. 2019 Mar 22; 2: 111.

Tech Ventures Reference:

• IR CU18018

• Licensing Contact: Kristin Neuman