MJ Fox Foundation Grant Aims for Way of Treating Dementia in Parkinson’s Patients

The Michael J. Fox Foundation (MJFF) has awarded a research grant to Asceneuron to develop small molecules with the potential to treat dementia related to Parkinson’s disease.

The grant, in an unspecified amount, from the MJFF Therapeutic Pipeline Program will:

• Support the further development of M1 PAMs (positive allosteric modulators of the M1 muscarinic acetylcholine receptor)
• Fund the study of molecule optimization to provide preclinical proof of concept in a relevant lab model

The M1 muscarinic acetylcholine receptor is important to a person’s learning and memory capability, and its modulators — M1 PAMs —  have the potential to treat cognitive deficits in Parkinson’s disease dementia (PDD) patients, as well as other conditions marked by dementia.

M1 PAMs lead to changes in the receptor’s shape, enhancing its capability to bind to the neurotransmitter acetylcholine. This process results in a potentiation of receptor activity that allows the receptor to fulfill its signaling functions, crucial for cognition. This happens even when acetylcholine levels are found to be reduced, as it is often observed in PDD patients.

“M1 PAMs could provide a new treatment option for Parkinson’s dementia, a critical current unmet need. We believe Asceneuron is making promising progress toward this goal,” Marco Baptista, PhD, MJFF’s director of research programs, said in a press release.

The most significant neurochemical deficit in PDD is cholinergic, which is activated or transmitter by acetylcholine, suggesting that approaches focused on acetylcholine transmission and modulation may be effective treatment options.

Grant money will also fund the study of molecule optimization to provide preclinical proof of the concept. Appropriate molecules have already been identified and Asceneuron has expertise in developing relevant central nervous system drugs, the company said.

“We are very excited to advance this approach to treating an underserved need. We expect our understanding of the novel biological interactions between M1 PAMs and the M1 muscarinic acetylcholine receptor to yield a Parkinson’s dementia therapy with potentially greater selectivity, fewer side effects and longer durability of effect,” said Dirk Beher, PhD, Asceneuron’s co-founder and chief executive officer.

Asceneuron, a Swiss company, is a developer of orally bioavailable small molecules targeting neurodegenerative diseases, like Parkinson’s or Alzheimer’s.

The increasing prevalence of dementia may be as high as 4.9 million worldwide, and it is most common in older patients.