URMC Start-up Takes Aim at Memory and Cognitive Problems

Apr. 30, 2015
Drug Developed at School of Medicine and Dentistry Targets Damaging Inflammation in the Brain

Medications are available to treat many of the symptoms of neurodegenerative diseases like multiple sclerosis and Parkinson’s disease, but there is no drug or other therapy that improves the memory and cognitive problems that often plague patients. A new start-up company, built around research conducted at the University of Rochester School of Medicine and Dentistry, hopes to change that.

Camber NeuroTherapeutics Inc., founded based on discoveries made in the laboratories of Harris “Handy” A. Gelbard, M.D., Ph.D. and Stephen Dewhurst, Ph.D., plans to attack the cognitive component of neurodegenerative diseases using a completely new approach: stopping the inflammation in the brain, so-called neuroinflammation, that impairs the function of nerve cells and the vast networks they create. These neural networks allow us to store and recall memories, plan and prioritize, focus on particular tasks, and process sensory information.

Gelbard, director of UR’s Center for Neural Development and Disease, says that neuroinflammation plays a role in multiple sclerosis, Parkinson’s, HIV-associated neurocognitive disorders (HAND), and postoperative cognitive dysfunction (POCD). Left unchecked, chronic inflammation in the brain leads to worsening cognition and can rob people of the ability to work, live independently and maintain their quality of life.  

Harris “Handy” Gelbard and Stephen Dewhurst

The company plans to combat neuroinflammation with a new class of drugs that Gelbard identified while studying HAND, the memory loss and overall mental fog that affects half of all patients living with HIV. (While HIV is thought of as a virus that attacks the immune system, it also attacks the brain.) The research was part of an NIH-funded program for new therapy development. The lead compound, dubbed URMC-099, turns off an enzyme called MLK3 (mixed lineage kinase type 3) that sets the neuroinflammatory process in motion.

URMC-099 successfully stopped inflammation and protected the brain in mouse models of HAND: results were reported in 2013 in the Journal of Neuroscience and the Journal of Medicinal Chemistry. Gelbard’s team has also tested URMC-099 in models of multiple sclerosis and they are extending their studies to models of Parkinson ’s disease and POCD. They believe the drug will exhibit similar anti-inflammatory activity in human studies.

“The same bad actors that are at play in HAND are also active in POCD, multiple sclerosis and Parkinson’s,” said Gelbard, referring to MLK3 and other related enzymes, which jumpstart inflammation in a wide range of disorders. “Our ultimate goal is to restore cognitive function and help people get their lives back. Based on data that we’ve gathered over the past eight years, we think we’ve found an extremely strong drug candidate with great potential.”

Camber NeuroTherapeutics will continue to conduct preclinical studies in 2015 and plans to submit an investigational new drug application (IND) for URMC-099 to the FDA and begin human trials in 2016.

“Camber provides us with the opportunity to translate the results of our basic science research into a first-in-human clinical trial, which is tremendously exciting,” said Dewhurst, vice dean for research and chair of the department of Microbiology and Immunology at the University of Rochester School of Medicine and Dentistry. “This would not have been possible without the NIH’s investment of more than $25 million in our research over 15 years, along with internal funding from the University’s Technology Development Fund and the guidance of expert colleagues in UR Ventures.  Having this ecosystem in place has made a huge difference."

The first in-human trial will be conducted in patients with POCD, a condition that affects approximately half of adults over the age of 65 who undergo major heart or orthopedic surgery. According to Mark Newman, M.D., an anesthesiologist and POCD expert at Duke Medicine, patients come out of surgery and can’t remember simple things or focus on more than one thing at a time. In some patients, cognitive problems resolve after a month or two, but in others they last much longer or become permanent.

Jim New, Ph.D., M.B.A., a senior executive with 34 years of pharmaceutical industry experience and the founder and CEO of Camber NeuroTherapeutics, says that no other company is testing a newly developed drug to treat POCD. Trials in people with HAND and other neurodegenerative diseases will follow.

The University of Rochester has granted Camber NeuroTherapeutics the worldwide patent rights to the drug candidates, including URMC-099. So far, the patents have been issued in the U.S., New Zealand and China and are pending in Europe, Canada, Japan, and Australia.   

The company is based at the Lennox Tech Enterprise Center in West Henrietta and currently employs three people, including New, who says that they plan to conduct as much of the research as possible in Rochester. Gelbard leads Camber NeuroTherapeutics’ scientific advisory board and Dewhurst serves on the board. (Gelbard and Dewhurst are not employees of the company.)