$5M grant funds new strategy to clear Parkinson’s proteins
Booster to use MJFF funding to study proteasome-activating molecules
A $5 million grant from The Michael J. Fox Foundation for Parkinson’s Research (MJFF) will help Booster Therapeutics develop therapeutics to improve the body’s ability to clear disease-causing proteins that drive Parkinson’s disease.
The research grant will support studies into small-molecule therapeutics that activate the proteasome, a cellular complex responsible for breaking down damaged or unnecessary proteins, as a strategy to treat neurodegenerative diseases. The goal is to find a promising drug candidate and test it in animals to see if it can be safely used in Phase 1 clinical trials.
“Parkinson’s disease is a disorder of the nervous system that worsens as unwanted proteins build up in the brain over time,” Diogo Feleciano, PhD, Booster’s co-founder and chief scientific officer, said in a company press release. “Proteasome activation has the potential to degrade deviant proteins that may be linked to Parkinson’s disease in a systematic fashion.”
Parkinson’s is caused by the progressive death of dopaminergic neurons, nerve cells responsible for making the signaling molecule dopamine. The loss of these neurons is associated with the accumulation of abnormal protein clumps called Lewy bodies and is thought to be tied to impaired proteasome function.
Current protein-degradation strategies tag single disease-causing proteins with ubiquitin, a protein marker, leading to their degradation by the proteasome, according to Booster. However, this does not address the broader proteasome dysfunction that occurs in neurodegenerative diseases such as Parkinson’s.
Targeting the proteasome
Booster’s approach aims to achieve widespread degradation of damaged proteins using compounds that directly activate the proteasome, allowing it to naturally recognize misfolded proteins without the need for ubiquitin tagging.
Booster says it’s used its proprietary DGRADX platform, which combines automated large-scale screening with advanced computational tools, to build a collection of small molecules with therapeutic potential for several diseases. Last year, the company said it had assembled an “extensive library” of compounds that it intends to use to develop potential clearance therapies.
The funded project, “Development of Small Molecule Proteasome Activators for the Treatment of Parkinson’s Disease,” aims to identify a novel small molecule that can cross the blood-brain barrier and activate the proteasome and reduce the accumulation of alpha-synuclein, the primary component of Lewy bodies. The blood-brain barrier, a semipermeable membrane that protects the brain and spinal cord, prevents certain medications from entering these organs.
The team will first identify biomarkers of proteasome activity and explore the effect of proteasome activators on biomarkers of Parkinson’s, including misfolded proteins and markers of nerve cell damage. Then, they will aim to develop a proteasome activator for clinical use and test it in animal models of Parkinson’s, in preparation for studies supporting its use in clinical trials.
“Developing treatments that target the root biological drivers of Parkinson’s is essential to delivering meaningful benefits for people living with the disease,” said Jessica Tomé Garcia, PhD, MJFF’s lead scientific program manager. “Through partnerships like our support of Booster Therapeutics, we aim to advance innovative approaches that strengthen the overall Parkinson’s therapy pipeline and move us closer to transformative treatments.”
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