MJFF awards second $2.5M grant to Selonterra for Parkinson’s research
Company is developing compounds targeting disease's genetic causes
The Michael J. Fox Foundation for Parkinson’s Research (MJFF) has awarded a second research grant of $2.5 million to Selonterra to advance the California-based company’s preclinical development of new therapeutic compounds targeting the genetic causes of Parkinson’s disease.
Selonterra specifically will be testing whether compounds that increase the activity of Parkin, a protein linked to familial cases of Parkinson’s, can improve cognition and help relieve some of the disease’s motor symptoms in preclinical models.
The preclinical testing will help determine whether the company’s most advanced compounds are safe for use in a Phase 1 clinical study in patients.
“MJFF’s funding of therapeutic development is a critical way we work to enable a diverse pipeline of treatments for people with Parkinson’s disease,” Brian Fiske, PhD, the foundation’s chief scientist, said in a Selonterra press release. “We greatly value our partnership with drug makers to equip them with resources to develop transformative results.”
First $2.5M MJFF grant funded Selonterra’s earlier research
Anne Urfer-Buchwalder, PhD, Selonterra’s co-founder and president, noted that Parkinson’s has “a strong genetic component” that the company’s research has targeted.
“The presence of shared dysfunctional pathways with other neurodegenerative disorders led us [toward] a basic common underlying mechanism operational in cognitive impairment,” Urfer-Buchwalder said. “With this new funding we will develop our small molecules to address these challenges for the benefit of Parkinson’s disease patients.”
Parkinson’s is marked by the progressive degeneration and death of the nerve cells in the brain that are responsible for producing the chemical messenger dopamine. The loss of dopamine leads to the disease’s manifestations, which comprise both motor and nonmotor symptoms.
Although what causes Parkinson’s is not fully known, several genetic mutations and variants have been strongly linked to the risk of developing the disease.
Selonterra is specifically developing therapies targeting a mutation in the SCNA gene called A53T, as well as the G2019S mutation in the LRRK2 gene. However, instead of focusing on the mutations’ effects on the proteins these genes produce, the company is developing small molecules that can normalize the activity of target genes near SCNA and LRRK2, Â whose activity may be dysregulated due to disease-causing mutations.
The presence of shared dysfunctional pathways with other neurodegenerative disorders led us [toward] a basic common underlying mechanism operational in cognitive impairment. … With this new funding we will develop our small molecules to address these challenges for the benefit of Parkinson’s disease patients.
The company previously had identified compounds that may improve the function of genes affected by SCNA and LRRK2 mutations. In another project also funded by MJFF, also in the amount of $2.5 million, Selonterra investigated whether restoring the activity of dysregulated target genes could improve cognitive and motor functions in Parkinson’s.
For that project, the researchers enhanced the structure of the test compounds so they could be administered orally, by altering their chemical structure and analyzing the effects on compound stability and activity. These new compounds were then tested in animal models of the disease.
The newly funded research will further support the preclinical development of compounds aiming to increase Parkin activity, and also advance the optimization of other compounds developed by Selonterra.
“We are very thankful for the continued grant support by The Michael J. Fox Foundation to build on our discoveries to make a meaningful impact on patients with Parkinson’s disease,” said Roman Urfer, PhD, Selonterra’s co-founder and CEO.
According to the company, the newly developed compounds may also be used to treat other conditions, particularly Alzheimer’s disease, characterized by cognitive issues and sharing common pathways with Parkinson’s.
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