While there are a number of gene therapy approaches in development for frontotemporal dementia (FTD), these only target known genetic causes of the disease such as mutations in the C9ORF72 gene. Unfortunately, the vast majority of FTD patients (> 70%), referred to as sporadic FTD patients, do not have a known genetic cause for their disease, despite the fact that FTD is a highly heritable disease and their form of FTD likely derives from genetic causes. Therefore, since many of the larger biopharma companies are focused on treating known genetic causes of FTD, AcuraStem has made a major push to identify therapeutic approaches that will work broadly across different types and for the majority of FTD patients. 

One of the most common features of neurodegenerative diseases is that the neurons in the brain have trouble clearing aggregated and misfolded proteins, and this ultimately results in the death of the neurons (neurodegeneration). It turns out that by reducing the function of PIKFYVE, you trigger the cells to engage an alternative method to clear these clogged proteins. This alternative method, called secretory autophagy, is highly innovative and has yet to be tested in the clinic for neurodegenerative diseases. 

Thus, AcuraStem is developing a therapeutic to suppress PIKFYVE. Our research has shown that suppression of PIKFYVE helps prevent degeneration of patient neurons in a dish, and strongly prevents loss of motor function in an FTD-relevant mouse model. The approach has been tested in multiple animals models and importantly has not caused toxicity in the human motor neurons nor in animal models. 

The objective of this project is to further validate the efficacy and safety of our development candidate ASOs. We will test the ASOs in neurons from several FTD patients and in mice to assess its efficacy and safety.