The University of Sheffield and Parkinson’s UK have combined forces to create Keapstone Therapeutics. The goal of the newly formed company is to help move research into nuclear factor erythroid 2-related factor 2 (Nrf2) through the development process and, hopefully, into testable treatments for Parkinson’s disease. Parkinson’s disease affects around 1 million people in the U.S. and 127,000 in the U.K.

Research on Nrf2 has been taking place at the University of Sheffield, while Parkinson’s UK is a nonprofit charitable foundation that has years of experience with, and dedicated funding for, Parkinson’s disease research. Parkinson’s UK formed the spinoff company, their virtual biotech venture, dedicated to a single asset: discovering and developing revolutionary medications for Parkinson’s disease. The term virtual biotech “means that the actual laboratory work will be outsourced (to Sygnature Discovery and Peak Proteins in the first instance), but managed by Keapstone,” said Thomas Bartlett, Ph.D., of Sheffield Healthcare Gateway.

According to James Beck, Ph.D., vice president of Scientific Affairs at the Parkinson’s Disease Foundation, a division of the Parkinson’s Foundation, “The idea of a virtual biotech entity is not new in general; however, having a charity in the driver’s seat is. There have been charities in the U.S. that have created daughter organizations. For example, the National Multiple Sclerosis Society, at one point, created Fast Forward as a separate entity that would make investments in the pharmaceutical industry. But this is not a virtual biotech per se. Overall, from the perspective of the Parkinson’s Foundation, which aims to both fill the pipeline with new ideas and drive drug development to improve lives now, this is an interesting approach to spurring drug development for our community.”

The virtual biotech was created to keep potential drugs from falling through the cracks that pose a hazard to early clinical development. The charity provides the funding and leadership, and its partners provide the scientific knowledge, research personnel and research facilities. Because of the single-asset focus, any potential treatment identified during the research phase can be funded appropriately and immediately move forward to clinical trials. The function is the same as a small biotech company, but without the commercial focus. The goal is simply to find new treatments that will improve quality of life for people living with Parkinson’s.

Keapstone is actually wordplay on the science that is key to its goals. Kelch-like ECH Associated Protein 1 (KEAP1) inhibits and degrades Nrf2. Nrf2 regulates the intracellular manufacture of antioxidants by initiating their gene transcription. A protein identified by Richard Mead, Ph.D., of the Sheffield Institute for Translational Neuroscience (SITraN), blocks KEAP1, allowing Nrf2 to do its job. This protein will be modified in the laboratory, and the most promising of the resulting, small drug-like molecules moved forward along the research pipeline.

“The Mead Keap1 project was chosen because the target is already quite well-validated and the compounds are more promising starting points for neurodegenerative disease drugs than any other compounds that have ever been discovered to inhibit the interaction between the proteins Keap1 and Nrf2,” said Bartlett.

Parkinson’s Disease Foundation’s Dr. Beck noted, “Research is an international endeavor and groups all over the world are looking into Nrf2 as one of many potential therapies for Parkinson’s. Keapstone’s approach is to create inhibitors that prevent the breakdown of Nrf2. There have been clinical trials of Nrf2 activators, which could achieve a similar biological effect.”

Parkinson’s researchers have also looked into administering large doses of antioxidant compounds, without a great deal of success. If a new treatment is developed that allows individuals to ramp up their own antioxidant defenses, their bodies can more effectively combat the oxidative stress caused when free radicals accumulate in brain neurons, as occurs with Parkinson’s. This amplified combative response could lessen, or perhaps even prevent, the neurodegeneration responsible for the disease.

Bartlett said, “Nrf2 activators directly address the degeneration of neurons so they may be preventative against Parkinson’s disease and motor neuron disease, but it is too early to tell until clinical trials.” However, promising breakthroughs in medications do not always translate to clinically testable drugs, as funding for development is not always forthcoming. Keapstone hopes to solve this problem for Parkinson’s medications.

Clinical trials are still five to 10 years away, assuming that testable medications come out of this research. At that point, Keapstone will hand the research over to the trial industry. “The plan is for Keapstone to be a preclinical development company,” said Bartlett.

Parkinson’s UK also focuses on improving clinical trials, making approval faster and easier by working with the government to clarify the regulatory process, thereby motivating companies to perform the needed research. Parkinson’s UK has so far promised 1 million pounds ($1.2 million) to Keapstone Therapeutics, with the commitment to continue funding as long as promising medications continue to be identified.

Companies in the U.S. have similar goals. The Michael J. Fox Foundation has its own internal team of researchers and project managers. The Parkinson’s Disease Foundation funds external research and fellowship programs, and participates in collaborative endeavors that focus on moving from “bench to bedside.”

Dr. Beck said, “The Parkinson’s Foundation is focused on ensuring that the pipeline is constantly filled early on with new compounds and is partnering with patients and clinical researchers to both accelerate and directly invest in clinical studies when new therapies are ready to be tested. For example, we recently announced half a million dollars toward clinical studies to meet unmet needs in Parkinson’s such as fatigue and cognitive difficulties. Together, these multifaceted approaches will help us create a world without Parkinson’s.”

He continued, “It’s critical that organizations such as the Parkinson’s Foundation and Parkinson’s UK—as representatives of the community’s urgency—play a role in ensuring that promising therapy ideas are never lost or unexplored due to lack of funding.” 

This article was reprinted from Volume 21, Issue 11, of CWWeekly, a leading clinical research industry newsletter providing expanded analysis on breaking news, study leads, trial results and more. Subscribe »