Collaboration to explore gene therapy for neurodegenerative disorders

Coave Therapeutics is collaborating with the Institute of Neurodegenerative Diseases (IMN) in Purdue to develop gene therapy proteins that target protein degradation in neurodegenerative disorders.

IMN is a joint research unit linking Bordeaux University and the French National Center for Scientific Research (CNRS) to develop gene therapy programs targeting protein degradation in neurodegenerative disorders.

The collaboration will explore the development of gene therapy products targeting transcription factor EB (TFEB) for the treatment of alpha-synucleinopathy, such as multiple system atrophy (MSA) and idiopathic Parkinson’s disease (PD).

Toxic protein aggregates

TFEB is a key regulator of the lysosomal autophagy pathway, a central cellular pathway that controls the degradation of toxic protein aggregates. Overexpression of TFEB via gene therapy demonstrates the potential to reduce and prevent the accumulation of toxic protein aggregates and thus prevent neurodegeneration

Erwan Bezard, IMN Research Director, Coave Scientific Advisory Board (SAB) member and Andrea Balbio, Scientific Director at Telethon Institute of Genetics and Medicine (TIGEM) also authored a research paper. It demonstrates a decrease in a-synuclein aggregates, preventing the destruction of dopaminergic neurons and restoring a clinical phenotype.

Parkinson’s disease

“Targeting the autophagy pathway with coAAV-based gene therapy is a unique approach to treating neurodegenerative diseases, such as Parkinson’s disease or multiple system atrophy,” Bezard said.

“Thanks to the partnership with Coave, IMN scientists have an important opportunity to confirm their scientific findings toward the clinic. We look forward to leveraging our collective strengths to develop the best gene therapy programs for neurodegenerative diseases with the potential to improve patient outcomes.”

Dr. Balabio, who discovered the role of TFEB as a key regulator of lysosomal biogenesis and autophagy, will be a consultant for this collaboration.

Rodolphe Clairval, CEO of Coave Therapeutics, said: “We are pleased to collaborate with IMN to develop coAAVs that carry TFEB and to explore these gene therapy combinations for the treatment of neurodegenerative diseases.

genetic therapies

“TFEB is an exciting target and we look forward to working with IMN and Andrea Ballabio to evaluate the impact of our new gene therapies from our ALIGATER platform for treating MSA and PD, with potential to develop other programs.”

Under the collaboration, Coave will use the AAV-Legand Conjugate (ALIGATER) platform to design, develop and manufacture coAAV viral vectors carrying the TFEB gene for targeted delivery into deep brain structures.

IMN will be responsible for conducting co-designed in vivo studies to assess the effect of gene therapy products in animal models of MSA and PD. The collaboration aims to create further in vivo proof of concept data and enable selection of therapeutic candidates for entry into IND enabling studies.