MJFF Grant Moves Potential Oral Therapy, ASN51, Into Early Testing

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by Margarida Maia, PhD |

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A research grant from The Michael J. Fox Foundation (MJFF) will allow Asceneuron to advance work on ASN51, a potential oral therapy for Parkinson’s disease.

The unspecified financial award, the foundation’s second to the company, will be used to move ASN51 into a preclinical study of a genetic model of early-onset familial Parkinson’s. Results of this work are expected by year’s end and, if positive, could support a clinical trial in people.

“We are proud to receive the continued support from a foundation that contributes meaningfully towards development of improved therapies for those living with Parkinson’s disease,” Dirk Beher, co-founder and CEO of Asceneuron, said in a press release.

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Parkinson’s is associated with the toxic accumulation of the alpha-synuclein protein in the brain and spinal cord, whose aggregated forms are thought to contribute to the loss of dopaminergic, or dopamine-producing, neurons.

Proteins can be modified after they are produced. Once such modification, called O-GlcNAcylation, is both a nutrient- and stress-responsive chemical modification that consists of the addition of a small sugar molecule to proteins to regulate their properties and function inside cells.

This chemical modification appears to be essential for healthy brain function. Research has shown that O-GlcNAcylation is reduced in aging brains, and that it works to suppress the aggregation and toxicity of alpha-synuclein. As such, blocking O–GlcNAcase (OGA) — the enzyme responsible for removing O-GlcNAcylation — holds the potential to prevent further damage in neurodegenerative diseases associated with a buildup of toxic protein clumps, such as Parkinson’s.

ASN51 is a suppressor of OGA. Previous work with an OGA inhibitor called ASN90 showed an ability to lower levels of both tau and alpha-synuclein proteins in a mouse model of Parkinson’s that carried a mutated form of the tau protein, resulting in better motor function and survival.

In the planned study of ASN51, the company will use a genetic model in which alpha-synuclein harbors a mutation called A53T that is known to cause an inherited form of early-onset Parkinson’s.

“The Michael J. Fox Foundation is dedicated to unlocking the complex biology of Parkinson’s disease and unearth novel breakthrough treatments to improve patient lives and slow disease progression,” said Luis Oliveira, PhD, the foundation’s senior associate director of research programs.

“We are pleased to award Asceneuron a grant to support further research in the O-GlcNAcase inhibitor, ASN51, as a potential modifier of [alpha]-synuclein toxicity,” Oliveira added.

Ascending doses of oral ASN51 were tested for safety and tolerability in healthy volunteers and Alzheimer’s disease patients in a three-part, Phase 1 clinical trial (NCT04759365) in Europe and Australia. Alzheimer’s, a neurodegenerative disease, is caused by the buildup of protein aggregates in the brain.

The trial was due to conclude in January, and it was supported by a $2.2 million grant from the Alzheimer’s Drug Discovery Foundation.