Acurastem wins $7.5M to advance ALS treatment to clinical trials
Company says California’s CIRM grant will help it move 'rapidly’
Written by |
- Acurastem secured $7.5M to advance AS-241, an ALS treatment, toward clinical trials.
- AS-241 targets TDP-43 protein abnormalities, a hallmark of ALS.
- The treatment aims to restore UNC13A protein levels, improving nerve cell communication.
Acurastem has received $7.5 million in funding from the California Institute for Regenerative Medicine (CIRM) to advance AS-241, its lead clinical candidate for amyotrophic lateral sclerosis (ALS) and related diseases, toward clinical trials.
The grant was supported by cell-based studies showing that AS-241 can restore certain ALS-related defects caused by problems with the TDP-43 protein, a hallmark of ALS, and by animal data suggesting the treatment is safe and leads to durable exposure in the brain and spinal cord.
The company previously received $4 million from CIRM to establish good manufacturing practices for AS-241 and conduct animal studies to assess the treatment’s safety, pharmacological properties, and effective dose ranges.
“CIRM funding undergoes one of the most rigorous scientific and translational review processes in the field,” Sam Alworth, Acurastem co-founder and CEO, said in a company press release. “Their support reflects strong confidence in the quality of our science and the therapeutic potential of AS-241.”
Alworth called the award “essential for helping us move AS-241 rapidly toward a Phase 1 clinical trial.”
Treatment aims to restore protein production
TDP-43 is a protein normally found in the nucleus (the cellular compartment where DNA is stored), where it is needed to process genetic information for protein production. One of TDP-43’s targets is a molecule that provides the genetic instructions for making the UNC13A protein, which is important for signal transmission between nerve cells.
In most ALS patients, TDP-43 is abnormal and forms toxic clumps outside the nucleus, preventing it from doing its normal job. As a result, the genetic instructions for making UNC13A are not properly processed, and levels of this protein are significantly reduced, leading to poorer ALS outcomes.
AS-241 is an antisense oligonucleotide (ASO) that binds to UNC13A’s genetic instructions and promotes adequate processing, restoring normal production of the UNC13A protein.
In preclinical studies, AS-241 was shown to restore normal UNC13A levels and improve the function of synapses, the regions where nerve cells communicate. Studies in animal models also supported the treatment safety and sustained exposure in the brain and spinal cord.
Acurastem says it designed AS-241 to act broadly across the disease population, as TDP-43 abnormalities are seen in about 97% of all ALS cases. This represents a major advance over Qalsody (tofersen), an approved treatment available only to the 2% of ALS patients who carry SOD1 gene mutations.
The company is working on additional therapies targeting TDP-43-related mechanisms. The experimental therapy AS-202, which is licensed to Takeda, is designed to block PIKfyve and activate waste-clearance mechanisms that help cells clear TDP-43 clumps.
Acurastem is also advancing therapies to target SYF, another protein involved in the processing of genetic information that is an important regulator of TDP-43 activity. Reducing SYF2 levels has been shown in lab models to help restore normal TDP-43 activity and reduce signs of neurodegeneration.
Leave a comment
Fill in the required fields to post. Your email address will not be published.