RARE Daily

AcuraStem Secures $7 Million from NIH and DOD to Accelerate Therapies for ALS and FTD

January 30, 2024

Rare Daily Staff

AcuraStem said it has received nearly $7 million in grant funding from the National Institutes of Health and the U.S. Department of Defense to support advancing its candidates for amyotrophic lateral sclerosis, frontotemporal dementia, and other neurodegenerative diseases toward clinical trials.

The grant funding builds on a recent licensing agreement with Takeda worth $580 million to develop and commercialize AcuraStem’s PIKFYVE targeted therapeutics.

AcuraStem Co-founder and CEO Sam Alworth said the agencies conducted a rigorous peer-reviewed process ahead of selecting AcuraStem for the awards.

AcuraStem has made a significant advancement in understanding the pathophysiology of ALS, focusing on the crucial role of UNC13A. An overwhelming majority of ALS cases, and roughly half of FTD cases, are characterized by TDP-43 pathology. TDP-43, an RNA-binding protein typically found in the nucleus, is mis-localized to the cytoplasm in affected neurons, leading to RNA processing errors. These errors result in the incorporation of a cryptic exon into the UNC13A messenger RNA, causing a loss of UNC13A protein. This loss is further exacerbated by a risk variant in the UNC13A gene, closely linked to the TDP-43 binding site and associated with reduced survival in ALS and FTD patients.

AcuraStem’s iNeuroRx platform has successfully replicated UNC13A pathology in patient neurons and enabled rapid development and testing of antisense oligonucleotides. These ASOs effectively suppress the cryptic exon and restore normal UNC13A function, offering a promising therapeutic approach for TDP-43 proteinopathies and a deeper understanding of UNC13A’s role in disease progression.

Additionally, AcuraStem has made a pivotal discovery with its focus on SYF2, a novel target in TDP-43 pathology. In collaboration with co-founder Justin Ichida’s lab at USC, AcuraStem’s extensive research on patient neurons via the iNeuroRx platform, coupled with a comprehensive bioinformatic analysis, identified SYF2 as a key therapeutic target. SYF2, a pre-mRNA splicing factor, plays a crucial role in the regulation of splicing affected by the depletion of nuclear TDP-43, a common feature in most ALS cases.

The company’s findings highlight that SYF2 can address both the toxic aggregation of TDP-43 in cytoplasm and also counter the widespread gene dysregulation, including critical genes like UNC13A and STMN2, caused by TDP-43’s absence from the nucleus. Targeting SYF2 could offer a more direct and potentially effective therapeutic strategy compared to addressing each dysregulated gene individually.

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