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Fox Foundation Funds New Genetic Variation Targets for Parkinson’s

Healthy neuron illustration

Healthy neuron illustration (NIH, Flickr.

8 Mar. 2023. A Parkinson’s disease organization is giving a grant to a neurodegenerative therapies developer that targets new groups of underlying disease-causing genetic changes. Selonterra Inc. in San Mateo, California says the Michael J. Fox Foundation is awarding the biotechnology company $2.5 million to find new targets for therapies in connections between genetic variations responsible for Parkinson’s disease and clinical dysfunctions of the disorder.

Selonterra is a six year-old enterprise discovering treatments that address root genetic causes of neurodegenerative disorders such as Alzheimer’s and Parkinson’s disease. Parkinson’s disease occurs when brain cells making the neurotransmitter dopamine die or stop making the chemical. Dopamine is a versatile hormone that sends messages from neurons or nerve cells in the brain throughout the body and is associated with a range of physical and cognitive functions, including movement, memory, pleasure rewards, motivation, behavior, mood, and learning. The Michael J. Fox Foundation estimates nearly one million people in the U.S. and more than six million worldwide are affected by Parkinson’s disease.

The Selonterra technology seeks genetic targets for small molecule or low-molecular weight drugs caused by variations in the amino acid chemistry of genes, called single nucleotide polymorphisms or SNPs. If a SNP affecting brain cells malfunctions, says the company, its transcription can affect not only the original gene, but also start a chain of repeated malfunctions in the chromosome, thus affecting nearby genes.

Treatments addressing malfunctions in nearby genes

A paper by Selonterra founders Anne Urfer-Buchwalder and Roman Urfer, published in Jan. 2017 in the journal Scientific Advances, identifies a specific SNP in the apolipoprotein E or APOE4 gene associated with Alzheimer’s disease. The authors then describe the SNP’s transcription mechanism that affects expression of multiple genes in the vicinity of APOE4, and map expression and transcription of these nearby genes to degeneration of nerve cells characteristic of Alzheimer’s disease. Selonterra says it discovers treatments addressing malfunctions in these nearby genes that the company calls the real causes of neurodegenerative disorders, offering new and as yet unexploited targets for treatments.

“The contribution of genetics to Parkinson’s disease is undisputed,” notes company president Anne Urfer-Buchwalder in a Selonterra statement released through Cision. “In contrast to an involvement of the proteins encoded by these genetic variants, our focus on the DNA sequence and the genes that these DNA variants control offers fundamentally different therapeutic opportunities.” Roman Urfer is Selonterra’s CEO.

Selonterra says it’s receiving a $2.5 million award from the Michael J. Fox Foundation or MJFF to find connections between these novel targets and clinical dysfunctions associated with Parkinson’s disease, which the company says can help optimize its small molecule drugs. The Selonterra pipeline has four candidates in preclinical development, with treatments for Parkinson’s disease targeting variations of the synuclein alpha or SNCA and leucine rich repeat kinase 2 or LRRK2 genes that code for proteins in the brain, and with mutations linked to Parkinson’s disease.

“MJFF greatly values research that takes fresh looks at the biological underpinnings of Parkinson’s disease and leverages that insight for new treatment ideas,” says the foundation’s co-chief scientist Brian Fiske. MJFF has an ongoing research project to identify biomarkers associated with the onset and progression of Parkinson’s disease.

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