Technologies broaden company’s ability to develop drugs for CNS and orphan diseases.
Proteostasis Therapeutics acquired two exclusive licenses from Harvard University to technologies that enhance the activity of the ubiquitin-proteasome pathway, a cellular protein clearance mechanism. The deal covers targets and small molecule compounds.
The technologies arose from research in the laboratories of Daniel Finley, Ph.D., professor of cell biology, Randall King, Ph.D., M.D., associate professor of cell biology, and Alfred Goldberg, Ph.D., professor of cell biology. Through the ubiquitin-proteasome pathway, proteins are first tagged by ubiquitin molecules and then degraded in the proteasome complex. Drs. Finley and King have identified a cellular enzyme, Usp14, which removes ubiquitin tags, inhibiting the breakdown of ubiquitin-targeted proteins.
They further identified small molecule inhibitors of Usp14 that accelerate the degradation of several neurodegenerative disease-related proteins such as tau, TDP-43, and ataxin-3, which are linked to Alzheimer disease, frontotemporal dementia, amyotrophic lateral sclerosis, and polyglutamine expansion diseases such as Huntington disease.
Their research also has led to the discovery of targets and small molecules that affect the proteasome’s gating mechanism. The development of compounds that regulate proteasome gating may result in therapeutics that increase the protein degradation capacity of disease-relevant proteins such as tau and α-synuclein, which have been linked to Alzheimer disease and Parkinson disease.
“Protein clearance mechanisms along with cellular pathways governing protein folding and trafficking are the cornerstones of the proteostasis network that maintain proper protein function,” notes Peter Reinhart, Ph.D., president and CSO of Proteostasis.
“Proteostasis is building a novel drug discovery platform for discovering and developing disease-modifying therapeutics that regulate the proteostasis network. These licenses from Harvard provide us with multiple novel targets and compounds that complement our existing programs, which are focused on other pathways within the proteostasis network.”
Dr. Reinhart notes that the company has predevelopment programs aimed at altering folding and trafficking pathways to treat diseases like Parkinson, Alzheimer, and Huntington diseases as well as cystic fibrosis. The firm’s small molecule candidates are called proteostasis regulators.