AcuraStem – a patient-based biotechnology company advancing treatments for amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and other neurodegenerative diseases – announced that it has successfully raised nearly $7 million in grant funding for ALS / FTD research from the National Institutes of Health (NIH) and the Department of Defense (DOD).
This latest achievement — which builds on the recent licensing agreement with Takeda worth $580 million to develop and commercialize AcuraStem’s PIKFYVE targeted therapeutics, including AS-202 — enables the company to advance multiple programs towards clinical trials.
AcuraStem significantly advanced 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 mislocalized to the cytoplasm in affected neurons, leading to RNA processing errors. And these errors result in incorporating 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, enabling the rapid development and testing of antisense oligonucleotides (ASOs). And 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.
Plus, AcuraStem has made a pivotal discovery with its focus on SYF2, a novel target in TDP-43 pathology. In collaboration with co-founder, Dr. Justin Ichida’s lab at USC, AcuraStem’s 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 (Linares GR et al. Cell Stem Cell 2023).
AcuraStem’s findings highlight that SYF2 can address 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. And targeting SYF2 could offer a more direct and potentially effective therapeutic strategy compared to addressing each dysregulated gene individually.
The funding from NIH and the DoD was awarded through rigorous peer-reviewed processes, suggesting the award matches the health missions established by each agency.
KEY QUOTE:
“We are thrilled to receive continued support from NIH and the DOD. Leaders from the scientific community selected AcuraStem for these awards through a rigorous peer-review process, which demonstrates the excellence of our research.”
– Sam Alworth, MS, MBA, AcuraStem co-founder and CEO
