AcuraStem receives $4M grant to advance ASO treatment for ALS
Company will set manufacturing processes, conduct animal studies
AcuraStem has received $4 million in funding from the California Institute for Regenerative Medicine (CIRM) to advance the development of AS-241, an investigational treatment strategy for amyotrophic lateral sclerosis (ALS) and related diseases.
AS-241 is an antisense oligonucleotide (ASO), a type of small molecule that binds to RNA and is designed to restore normal function of the UNC13A protein, which is commonly impaired in ALS and associated with decreased survival chances.
The project, “Development of AS-241, an UNC13A Targeting Antisense Oligonucleotide (ASO) Treatment for ALS, for IND-enabling Studies,” aims to establish good manufacturing practices for AS-241 and conduct animal studies to assess its safety, pharmacological properties, effective dose ranges.
The data is expected to support a pre-investigational new drug meeting with the U.S. Food and Drug Administration to obtain feedback on the design and requirements for clinical studies.
“The support from CIRM is a testament to the potential of our research and its capacity to address critical challenges in neurodegenerative disease treatment,” Sam Alworth, co-founder and CEO of AcuraStem, said in a company press release. “This funding will facilitate the development of our UNC13A program toward clinical trials, enabling us to leverage our advances to potentially revolutionize the treatment landscape for ALS.”
Binding ASO treatment to faulty mRNA
In about 97% of ALS patients, a misfolded version of the TDP-43 protein forms toxic clumps that contribute to the dysfunction and death of motor neurons, the nerve cells that control voluntary movements.
TDP-43 is normally found in the nucleus, the cellular compartment where genetic material is stored and where it is involved in the processing of messenger RNA (mRNA), an intermediary molecule needed for protein production. As the protein forms abnormal clumps in the cytoplasm of people with ALS, its normal function is disrupted.
One of TDP-43’s targets is the mRNA molecule that caries the instructions for making the UNC13A protein. When TDP-43 cannot exert its function, a genetic sequence called a cryptic exon is erroneously included in the mature UNC13A mRNA, which reduces the amount of protein being produced. This is further exacerbated in patients carrying mutations in the UNC13AÂ gene, which lowers survival chances and disease outcomes in people with ALS.
AcuraStem is developing antisense oligonucleotides that bind to the faulty UNC13A mRNA and prevent the cryptic exon from being read during protein synthesis, restoring the normal production of the UNC13A protein.
Using its iNeuroRx platform, which couples patient-derived disease models with human genetic data, the company was able to replicate key aspects of the disease in patient-derived neurons. This allowed researchers to test multiple compounds that could suppress the cryptic exon in UNC13A mRNA, which ultimately led to the discovery of AS-241.
According to the company, preliminary data demonstrated that AS-241 is safe and likely effective.
iNeuroRx also enabled the discovery of other potential therapeutic targets for ALS, including SYF2, another protein in the nucleus involved in mRNA processing. Modulating SYF2 may reduce the toxic accumulation of TDP-43 and improve its mRNA processing function.
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