BioMotiv, a drug development accelerator associated with The Harrington Project, the University of California San Francisco (UCSF) and University of Washington, Seattle, have announced the formation of OptiKira, a platform company that will develop small molecule therapeutics that prevent cell death in pathologies caused by misfolded or unfolded proteins.
OptiKira is based on intellectual property exclusively licensed from UCSF and University of Washington.
The project was initiated at UCSF and the University of Washington by scientific founders Scott Oakes, M.D., associate professor of pathology at UCSF; Feroz Papa, M.D., Ph.D., associate professor of medicine at UCSF; Bradley Backes, Ph.D., associate professor of medicine at UCSF; and Dustin Maly, Ph.D., associate professor in chemistry at University of Washington.
Oakes and Papa are members of the first class of Harrington Scholar-Innovators, an annual grant competition implemented by the Harrington Discovery Institute at University Hospitals in Cleveland, Ohio—part of The Harrington Project for Discovery and Development—that enables inventors' discoveries to be advanced towards preclinical proof-of-principle.
Extensive research by the founders has helped define the biological pathway leading to progressive cell death which characterizes diseases such as retinitis pigmentosa, diabetes and amyotrophic lateral sclerosis (ALS). They have found the unfolded protein response (UPR), a mechanism by which the cell deals with functionally abnormal proteins, has an important housekeeping role in cell metabolism. However when overloaded, the "terminal UPR" results in the accumulation of excessive unfolded proteins and cellular death.
The team has synthesized inhibitors of IRE1a to prevent the activation of the terminal UPR, while not disrupting the housekeeping role of the enzyme. They have demonstrated that inhibitors of IRE1a, which they have named kinase-inhibiting RNase attenuators (KIRAs), protect cells from degeneration in preclinical models of retinitis pigmentosa and diabetes.