Coave Therapeutics, a company specialising in developing genetic medicines, has announced its status as one of six organisations sharing $2.9 million in grants from the ALS Association.
The organisation supports the advancement of novel therapies for the treatment of amyotrophic lateral sclerosis (ALS).
The grant, which will support the development of Coave’s CTx-TFEB programme through to preclinical proof-of-concept, has been made through the Association’s Lawrence and Isabel Barnett drug development programme.
ALS is a progressive neurodegenerative disease that affects nerve cells in the brain and spinal cord. Over the course of the disease, people lose the ability to move, to speak, and eventually, to breathe.
The disease is always fatal, usually within five years of diagnosis. There is currently no cure
While more than 40 different genes have been linked to ALS, the majority of cases are considered “sporadic.” On average, it takes about a year before a final ALS diagnosis is made.
The disease is always fatal, usually within five years of diagnosis. There is currently no cure.
The neuronal accumulation of toxic protein aggregates is a common feature of many neurodegenerative diseases.
In most people with ALS, such toxic clumps negatively impact the function of brain and spinal cord motor neurones, thus leading to their progressive degeneration.
While healthy cells can break down protein aggregates through a process known as autophagy, this process has been shown to be strongly dysregulated in ALS.
It’s anticipated that increasing autophagy could promote the clearance of accumulated toxic material and thereby halt both motor neurone degeneration and ALS progression.
CTx-TFEB is a novel genetic medicine approach designed by Coave to promote autophagy in ALS patients irrespective of genetic subtype, offering the possibility of creating a pan-ALS therapy.
CTx-TFEB leverages Coave’s ALIGATER platform and comprises a conjugated AAV (‘coAAV’) that enables the targeted delivery of transcription factor EB (TFEB) gene to neurones in the brain and spinal cord.
TFEB has recently emerged as a ‘master activator’ of the autophagy-lysosomal (ALP) pathway. Indeed, while reduced TFEB protein levels in brain and spinal tissues are associated to the accumulation of protein aggregates, enhancing autophagy through TFEB activation promotes ALP function thus leading to the clearance of such aggregates.
Lolita Petit, CSO of Coave Therapeutics, commented: “Modulating autophagy using TFEB gene therapy is an exciting approach to promote the clearance of accumulated toxic material in affected neurones, halt motor neurone degeneration and preserve muscular function in people with ALS. With this funding and invaluable support from the ALS Association, we are poised to move our CTx-TFEB program forward. Our goal is to establish a robust preclinical proof-of-concept, laying a strong foundation for advancing to the clinic in the near future. Together, we are now on the brink of a breakthrough that promises hope and progress for patients impacted by ALS.”
