AcuraStem awarded NIH, DOD grants to boost ALS therapies

Funding follows $580M deal with Takeda to license PIKfyve-targeting therapy

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by Steve Bryson, PhD |

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AcuraStem has secured nearly $7 million in grant funding from the National Institutes of Health (NIH) and the Department of Defense (DOD) to accelerate the development of therapies for amyotrophic lateral sclerosis (ALS) and related diseases.

Coming on the heels of a $580 million deal with Takeda, which obtained an exclusive, worldwide license to AcuraStem’s investigational therapies that target the PIKfyve enzyme, the new funding, awarded via a peer-review process, will help the company advance several other programs toward clinical trials.

“We are thrilled to receive continued support from NIH and the DOD,” Sam Alworth, MS, AcuraStem’s co-founder and CEO, said in a company press release. “Leaders from the scientific community selected AcuraStem for these awards through a rigorous peer-review process, which demonstrates the excellence of our research.”

Nearly all ALS patients, including those with sporadic or familial ALS, accumulate a misfolded version of the TDP-43 protein in nerve cells. Normally found inside the nucleus, abnormal TDP-43 forms clumps outside it, which disrupts the function of motor neurons, the nerve cells that control voluntary movement.

The Takeda deal covers therapies, including AS-202, which is designed to target and block PIKfyve. Blocking this enzyme activates multivesicular body (MVB) exocytosis, a process that removes waste and unwanted proteins from cells.

By activating this process, AS-202 should promote the clearance of abnormal TDP-43 and prevent the neurodegeneration that marks ALS and frontotemporal dementia (FTD), a related condition also caused by TDP-43 clumping.

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 Funding covers other therapeutic programs

The NIH and DOD funding will also advance the development of therapies that target UNC13A and SYF2, programs not covered by the Takeda licensing agreement.

Inside the nucleus, TDP-43 normally acts as an RNA-binding protein involved in processing messenger RNA (mRNA), an intermediary molecule produced as part of protein production.

When abnormal TDP-43 moves outside the nucleus, it disrupts the processing of UNC13A mRNA, leading to a loss of the UNC13A protein. This loss, which is worsened by mutations in the UNC13A gene, is associated with reduced survival in ALS and FTD patients.

The company’s iNeuroRx platform, which couples patient-derived disease models with human genetic data, was able to replicate UNC13A-related disease in patient neurons, according to AcuraStem.

Building on these findings, the company has developed antisense oligonucleotides (ASOs), a class of DNA/RNA-binding small molecules that prevent the disruption of UNC13A mRNA processing by TDP-43, thereby restoring UNC13A function.

These advances offer “a promising therapeutic approach for TDP-43 proteinopathies [protein-clumping diseases] and a deeper understanding of UNC13A’s role in disease progression,” AcuraStem wrote in its release.

The company says it’s also discovered that SYF2, another protein in the nucleus that’s involved in mRNA processing, is a potential ALS target. SYF2 regulates mRNA processing, which is affected by the movement of TDP-43 out of the nucleus. Modulating SYF2 may address both the toxic buildup of TDP-43 and counter the widespread dysregulation of genes, including UNC13A.

“Targeting SYF2 could offer a more direct and potentially effective therapeutic strategy compared to addressing each dysregulated gene individually,” AcuraStem noted.