AcuraStem Receives Target ALS Grant to Develop SYF2-Targeted Therapeutics for TDP-43 Dysfunction
Key Insights
AcuraStem (search) has been awarded a two-year research grant from Target ALS (search) to advance therapeutics targeting SYF2 (search), a pre-mRNA splicing factor that regulates TDP-43 function in amyotrophic lateral sclerosis (search).
The grant will support mechanistic studies of SYF2 (search) modulation, which has shown promise in preclinical models for restoring normal TDP-43 activity and protecting motor neurons from degeneration.
The research collaboration includes Johns Hopkins University (search) and Mayo Clinic Jacksonville investigators, focusing on TDP-43 dysfunction present in the vast majority of ALS (search) cases.
AcuraStem (search), a patient-based biotechnology company developing disease-modifying therapies for amyotrophic lateral sclerosis (search) (ALS (search)), has received a two-year research grant from Target ALS (search) to advance therapeutics targeting SYF2 (search), a recently identified regulator of TDP-43 function. TDP-43 dysfunction represents a central biological hallmark of ALS, making this research particularly significant for addressing the core pathology of the disease.
Novel Therapeutic Target Shows Promise in Preclinical Models
The Target ALS (search) Drug Discovery Consortium award will support mechanistic and translational studies of SYF2 (search), a pre-mRNA splicing factor whose modulation has demonstrated the ability to restore normal TDP-43 activity and protect motor neurons in preclinical models. The therapeutic approach holds particular promise because TDP-43 dysfunction is present in the vast majority of ALS (search) cases, including sporadic disease, potentially benefiting a broad patient population.
"For most people living with ALS (search), the disease is driven by the dysfunction of TDP‑43, but there are still no effective treatments that target this core pathology," said Sam Alworth, M.S., MBA, co‑founder and CEO of AcuraStem (search). "This project will accelerate our understanding of SYF2 (search) biology and help lay the groundwork for future SYF2-targeted medicines."
Multi-Institutional Collaboration Leverages Complementary Expertise
Under the award, AcuraStem (search) will collaborate with leading academic investigators, including Philip C. Wong, Ph.D. from Johns Hopkins University (search), and Wilfried Rossoll, Ph.D. from Mayo Clinic Jacksonville. The collaboration unites complementary strengths in TDP-43–dependent RNA splicing and fluid biomarker development from the Wong laboratory with cutting-edge proteomics and neuroproteostasis expertise focused on TDP-43 proteinopathy from the Rossoll laboratory.
The multidisciplinary team will work alongside AcuraStem (search)'s patient-derived ALS (search) motor neuron platforms and SYF2 (search)-targeted antisense oligonucleotide to define how SYF2 modulation reshapes TDP-43 RNA processing, protein interactomes, and ALS-relevant neuronal phenotypes. This comprehensive approach aims to establish a rigorous mechanistic framework to advance SYF2-targeted therapeutics toward clinical development.
Scientific Foundation Built on Collaborative Research
SYF2 (search) was initially identified as a regulator of TDP-43 biology through collaborative research with Justin Ichida, Ph.D. from the University of Southern California. Subsequent work by AcuraStem (search) and Ichida laboratory scientists demonstrated that suppressing SYF2 alleviates TDP-43 pathology and neurodegeneration (search) in ALS (search) models, providing the scientific rationale for advancing SYF2-targeted therapeutics.
The research builds on AcuraStem (search)'s iNeuroRx® platform, which enables the discovery and development of broadly acting, disease-modifying therapies using patient-derived cellular models. The company focuses on developing treatments for neurodegenerative diseases, including sporadic ALS (search) and frontotemporal dementia (search) (FTD (search)).