Biotechnology company AcuraStem has been awarded a $4 million grant from the California Institute for Regenerative Medicine (CIRM) to further its research into targeted therapeutics for amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The funding will support AcuraStem's program focused on the UNC13A gene, which is crucial in the progression of both ALS and FTD.
Targeting UNC13A Dysfunction
AcuraStem is utilizing its proprietary iNeuroRx platform to develop targeted therapeutic compounds designed to address UNC13A dysfunction resulting from the loss of function in the TDP-43 protein. Cases of ALS and FTD associated with TDP-43 often exhibit this dysfunction and abnormal accumulations of the protein. The UNC13A gene encodes a protein essential for neurotransmission, facilitating communication between neurons and playing a role in synaptic plasticity, which is vital for motor control, learning, and memory.
In ALS and FTD caused by TDP-43 pathology, the function of UNC13A is disrupted. When TDP-43 loses its normal function, disruptive segments of RNA called cryptic exons can slip into the messenger RNA, which carries blueprints to create UNC13A protein. This disruption leads to a significant decrease in functioning UNC13A protein, impairing the neurotransmission process.
Antisense Oligonucleotides (ASOs) to Restore Function
AcuraStem's iNeuroRx platform recreates a model of TDP-43 pathology using blood or skin samples from ALS or FTD patients. This model, which includes living neurons and support cells, allows researchers to observe genetic expression dysfunction closely. The company employs machine learning and other techniques to study the model and identify compounds that can restore normal cell function.
The platform has enabled AcuraStem to develop and test antisense oligonucleotides (ASOs), short synthetic strands designed to bind to specific mRNA sequences. These ASOs bind to the cryptic exons in UNC13A created by TDP-43 pathology, suppressing them and allowing UNC13A to resume its regular functions.
Clinical Potential
The CIRM grant will support AcuraStem as it advances its ASOs for ALS and FTD through the preclinical stage of research. Previously, the company developed an ASO for the PIKFYVE enzyme. This earlier ASO was licensed to Takeda Pharmaceuticals and is currently undergoing clinical trials.
