PALO ALTO, Calif., May 3, 2018 /PRNewswire/ -- In a new study just published in the journal Nature, researchers have discovered patterns of abnormal brain activity that produce motor deficits in Parkinson's disease (PD). PD is the second most common neurodegenerative disease affecting 10 million individuals worldwide, and while it is one of the brain diseases where treatments do exist, current therapeutics are far from optimal and no cure exists. The study, a multi-year collaboration between Dr. Mark Schnitzer at Stanford University and Dr. Michael Ehlers, formerly Group Senior Vice President, BioTherapeutics at Pfizer, and now Executive Vice President, Research & Development at Biogen, offers hope that new therapeutics can be developed based on their ability to correct abnormal brain circuit activity.
The researchers used state-of-the-art brain imaging technology, a miniature microscope-based platform from the Silicon Valley neurotechnology company, Inscopix, to peer into a brain region called the striatum in a mouse model of PD. By monitoring activity in hundreds of neurons simultaneously in the living brain, they observed aberrations in striatal activity patterns that encode voluntary movement. The researchers then tested compounds like L-DOPA, the mainstay PD treatment, and other dopamine agonists that have proven to be less efficacious than L-DOPA in the clinic, and found significant correspondence between a compound's ability to correct the pathological striatal activity patterns and its clinical efficacy.
"The striatal circuits of motor control are critical for disease states such as Parkinson's disease, and restoration of neural ensemble function holds great potential as a circuit endophenotype for therapeutic development," said Dr. Ehlers, the study's co-lead. "Visualization of hundreds of genetically-defined neurons during behavior, in disease models, and in response to systemic pharmacological intervention represents a novel paradigm for preclinical drug testing. This study highlights the new era of neurotherapeutic development that we are entering."
Such a neural circuit-based approach holds great promise for pre-clinical neurotherapeutic development as it provides an objective and quantitative measure for evaluating efficacy of candidate therapies directly in the brain. PD drug development has traditionally used restoration of motor behavior in animal models as a predictor of the compound's clinical efficacy. Unfortunately, animal behavior has been a poor predictor of human clinical efficacy. Indeed, in the research reported, the clinically less successful dopamine agonists corrected motor behavior deficits, but did not correct the abnormal striatal circuit patterns, suggesting that circuit-based screening accurately predicts clinical efficacy (or lack thereof).
Inscopix plans to build on the results of this study and develop the first neural circuit-based assay for preclinical testing and development of therapeutics for PD.
About Inscopix, Inc.
Inscopix is pioneering a new paradigm in the quest to understand the brain and its diseases. Inscopix has developed the means to relate neural circuit dynamics to corresponding behavior. With its flagship products, nVista and nVoke, Inscopix is today disseminating these capabilities to neuroscientists across the world, empowering them to gather unprecedented data sets and make breakthrough scientific discoveries. With in-house and field-based neuroscience expertise combined with strategic collaborations around the world, Inscopix stands at the brink of making fundamental advances in brain research and pharmaceutical development for neurological diseases.
SOURCE Inscopix, Inc.