Nicotinic acetylcholine (nAChRs) receptors are ligand-gated ion channels that are activated by acetylcholine under physiological conditions. The α6 subtype exhibits an extremely localized expression mainly confined to dopaminergic neurons in the area of the brain affected in Parkinson’s disease patients where they act as important regulators of dopamine signaling.
As a result of a focused screening campaign, Saniona has identified selective positive allosteric modulators (PAMs) of α6 containing receptors and furthermore demonstrated that these PAMs increase the affinity for acetylcholine. Given the restricted expression pattern of α6-containing nAChRs, selective PAMs could therefore provide a novel therapy to increase dopaminergic signaling in Parkinson’s disease patients. In addition, α6 selective PAMs have the potential to slow or stop neurodegeneration seen in Parkinson’s disease that could result in stabilization of symptoms and disease progression. The identified PAMs offer a novel approach to counteract degeneration of dopaminergic neurons in patients and could optimally be used as a disease modifying therapy against Parkinson’s disease.
Parkinson’s disease is a chronic and progressive neurological disorder that is characterized by well-known motor symptoms including tremors, stiffness of limbs, slowness of movements, and difficulties with posture and balance. In addition to motor symptoms, many Parkinson’s disease patients experience non-motor symptoms, including sleep disorders, sensory symptoms, depression and gastrointestinal symptoms. It is the second most common neurological disorder and more than five million people worldwide live with this disease.
Saniona has received a grant from The Michael J. Fox Foundation for Parkinson’s Research to demonstrate relevant facilitation of dopamine neurons and to perform a chemical optimization of its nicotinic α6 modulators in order to identify compounds suitable to demonstrate activity in relevant animal models. Once an optimal tool compound is generated, Saniona will conduct functional proof-of-principle studies and assess potential neuroprotective effects. The program is in the drug discovery phase.