Excitotoxicity In the Motor System
With our exclusive access to Q-State’s advanced stem cell techniques, we are able to transform
patient derived skin cells into motor neurons. These cells are the ones affected by ALS and can
be used to test our various drug candidates on a patient population specific model in the lab. In
the Excitotoxicity program, we are able to test drug efficacy with the Optopatch technology,
allowing us to measure drug response in thousands of cells simultaneously.
Using these methods, decreased activity in the potassium channel protein Kv7.2/7.3 was
identified as a driver of hyper-excitability. QurAlis is developing next generation therapeutics to
target the Kv7.2/7.3 channel to help treat the population of ALA patients that present
Restoration of the autophagy pathways
Through large DNA sequencing efforts, the scientific community has now been able to identify almost 30 different genes that can cause ALS. These genes code for proteins which are potential targets for the development of precision medicine for ALS. Interestingly, a number of these genes belong to key cellular processes which appear to be causal to the disease when disrupted, such as the cellular waste clearance pathways; autophagy and mitophagy. It is through these waste clearance pathways that toxic protein buildups are removed from cells and through which old broken cellular components responsible for energy production are recycled. QurAlis has identified an enzyme which normally inhibits the autophagy pathways and is developing a drug candidate to inhibit this enzyme, hoping to bring the waste clearance pathways back to normal functioning levels. Our preclinical work is showing this drug candidate to be a potentially safe, targeted therapeutic to correct faulty autophagy pathway.
QurAlis is following a structure-based "intelligent" drug design approach, using a crystallized form of the target protein to guide the chemistry processes and make a molecule which is specific and potent. Last, QurAlis uses stem cells from ALS patients to ensure efficacy of our developed molecule in the lab before moving it into the clinic.