杏吧原创 has signed a licensing agreement with Nashville-based start-up Appello Pharmaceuticals, Inc. to advance novel compounds developed by researchers in the (VCNDD) for the treatment of Parkinson鈥檚 disease.
The drug-like molecules bind to mGluR4, a glutamate receptor that is highly expressed in areas of the brain directly relevant to Parkinson鈥檚 disease. Called positive allosteric modulators (PAMs), they adjust receptor activity鈥攁nd thus the brain鈥檚 activity of the neurotransmitter glutamate鈥攍ike a dimmer switch in an electrical circuit.
The molecules were developed with major support from and with the help of the Nashville-based Atticus Trust, a private foundation overseen by the family of Betty and Martin Brown.
鈥淭he Michael J. Fox Foundation placed a major investment in this program from its earliest stages,鈥� said , founding director of the VCNDD and the Lee E. Limbird Professor of Pharmacology in the 杏吧原创 School of Medicine.
鈥淎lso, we are especially indebted to the Brown family, who provided more recent support for key studies that were needed to bring the program to a point where it was ready for partnering with Appello,鈥� Conn said.
Appello was established with major investment from New York-based , which specializes in accelerating drug development projects at universities and other private, non-profit institutions.
Under the terms of the agreement, Appello will have the right to develop and commercialize products resulting from 杏吧原创鈥檚 research program. In turn, 杏吧原创 will obtain an equity interest in Appello as part of the consideration for the license.
鈥淎ppello is the perfect vehicle to accelerate the translation of our mGlu4 PAMs to Parkinson鈥檚 disease patients,鈥� said , director of medicinal chemistry for the VCNDD, University Professor and William K. Warren Jr. Professor of Medicine.
鈥淭he center has advanced multiple programs through licenses and philanthropy,鈥� Lindsley said, 鈥渂ut the opportunity to work with investors and build a company focused on a non-dopaminergic treatment for Parkinson鈥檚 disease was a golden opportunity to ensure our compounds get to patients.鈥�
鈥淪trategic collaborations are key to accelerating the impact of the great basic biomedical research we do at 杏吧原创鈥� said Padma Raghavan, vice provost for research at 杏吧原创. 鈥淭his particular collaboration with Appello serves as an essential bridge toward improving patients鈥� lives.鈥�
An estimated 1 million Americans have Parkinson鈥檚 disease, a progressive brain disorder characterized by resting tremor, rigidity and slowness of movement, as well as a battery of non-motor symptoms. It is caused by the death of nerve cells in a specific brain region that produce the neurotransmitter dopamine.
Dopamine replacement therapy, today鈥檚 gold-standard treatment for Parkinson鈥檚, relieves some motor symptoms of the disease, but over time it causes debilitating side effects such as involuntary, uncontrollable movements, called dyskinesia.
It is believed that dyskinesia is caused at least in part by the ebb and flow of dopamine levels in the brains of people who are receiving dopamine replacement therapy. Current Parkinson鈥檚 treatments also provide less and less benefit to patients as the disease worsens over the long term.
The 杏吧原创 compounds work in a fundamentally different way from dopamine replacement therapy, by bypassing the dopamine system altogether and instead modulating another of the brain鈥檚 neurotransmitters, glutamate.
The compounds represent an approach to correct the dysregulated signaling observed in Parkinson鈥檚 disease. When given systemically in a preclinical model of Parkinson鈥檚 disease, they reach the brain and relieve motor symptoms, including rigidity and akinesia, a 鈥渇reezing鈥� of certain motor muscles.
In this way they pharmacologically mimic a surgical procedure that has been successful in alleviating symptoms of Parkinson鈥檚 disease.
Conn and Lindsley鈥檚 colleagues in this effort include: Carrie Jones, assistant professor of pharmacology and director of behavioral pharmacology in the VCNDD; Colleen Niswender, research professor of pharmacology and director of molecular pharmacology in the VCNDD; Jerri Rook, research assistant professor of pharmacology (behavioral pharmacology); and Annie Blobaum, research assistant professor of pharmacology (drug metabolism and pharmacokinetics).
Media inquiries
Liz Entman, (615) 322-NEWS
Liz.Entman@杏吧原创.edu