Malvern, PA, Progenra Inc — June 16th, 2025 — Parkinson’s disease is the second most prevalent neurodegenerative disease and presents a global health challenge, effecting 10 million people world-wide. About 90,000 people are diagnosed with Parkinson’s disease in US every year. About 1.2 million people will suffer from Parkinson’s disease in US by year 2030, according to Parkinson’s Foundation. Most of the Parkinson’s disease cases occur late in age. However, specific genetic mutations lead to early onset of PD that account for about 5-10% of all cases of Parkinsons’s disease patients. Inactivating mutations in Parkin, a ubiquitin E3 ligase and PINK1, a kinase, present a significant population of inherited Parkinsons’s disease.
In a groundbreaking advance, researchers at Progenra Inc., have discovered a novel class of small-molecule PINK1 activators that restore functional activity in mutant forms of the PINK1 kinase, a key mitochondrial regulator whose dysfunction is implicated in familial or early onset Parkinson’s disease (PD). This discovery represents the first evidence that pharmacological activation of defective PINK1 variants—previously considered “loss-of-function”—is not only possible, but therapeutically viable.
“This is a paradigm shift,” said Dr. Kumar Suresh, PhD, Vice President of R&D at Progenra who spearheaded the program. “We’ve shown that specific pathogenic PINK1 mutations found in Parkinson’s patients can be functionally reactivated with small molecules, restoring their ability to sense mitochondrial stress and initiate mitophagy—a crucial process for clearing damaged mitochondria.”
Dysfunctional Mitochondria: Mitochondria are the energy factories of cells. PINK1/Parkin plays a critical role in mitochondrial quality control. Loss of PINK1/Parkin function leads to accumulation of dysfunctional mitochondria, contributing to neuronal death. Until now, these mutations were thought to result in irreversible inactivation, leaving patients with few therapeutic options targeting the root cause of the disease.
PINK1/Parkin Role in Neurodegenerative Diseases: Aggregation of proteins in neurons is the main cause of several neurodegenerative disorders. Tau protein aggregates for Alzheimer’s disease, alpha synuclein aggregates for Parkinson’s disease, TDP43 aggregates are responsible for Amyotrophic lateral sclerosis (ALS), to name a few. Protein aggregates damage mitochondria leading to loss of ATP and neuronal cell death. Aggregated proteins or proteinopathies such as Lewy Body disease are also responsible for dementia. The PINK1 activator drug removes protein aggregates, restores healthy mitochondrial function by removing the damaged mitochondria as well as generating new mitochondria. The dual acting function of the PIKP1 activator drug will also have a big impact on other neurodegenerative disorders.
Alzheimer’s disease, Parkinsons
Key Highlights of the Discovery:
- First demonstration of mutant PINK1 reactivation via small-molecule pharmacology.
- Restores mitochondrial stress response and synthesis of new mitochondria.
- Foundation for precision medicine targeting genetically defined Parkinson’s patients.
Since the PINK1 activator drug removes protein aggregates and restores mitochondrial health, its application for Lewy body disease and other proteinopathies are also apparent. “This discovery opens an entirely new avenue for neurodegenerative diseases and especially for personalized medicine for PD patients,” added Dr. Tauseef Butt, PhD, President& CEO of Progenra Inc. “Instead of compensating for PINK1 loss, we can now target the defective protein directly, potentially halting disease progression at its origin.”
The team is now advancing these PINK1 activators into preclinical development, with the goal of initiating first-in-human studies within the next two years.
About Progenra Inc:
Progenra (www.progenra.com), a privately held company, aims to discover and develop novel medicines exploiting ubiquitin proteasome pathways. Utilizing the company’s UbiPro™ Drug Discovery Platform, Progenra have identified and are developing novel modulators of PINK1/Parkin signaling pathway as therapeutics for treating neurodegenerative and mitochondrial diseases such as Parkinson’s, Alzheimer’s as well as cardiovascular diseases.
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