NeuroNEXT: New Neuroscience Network Aims to Speed Up Phase 2 Trials

Abstract

“One important question is whether drugs acting on mTORC1 signaling might have the same anti-dyskinetic effect of rapamycin without causing immune suppression,” he said. “Another question is whether rapamycin or analogues to it can counteract dyskinesia once it has been established. In our initial study, we only showed that the development of dyskinesia is reduced when you give rapamycin at the same time you begin L-DOPA therapy.” Whereas the drugs already in clinical trials for dyskinesia act upon neurotransmitter receptors, all three of the approaches presented at the symposium target defects occurring within the striatal neurons themselves, Dr. Fisone said. “This concept of targeting intracellular signalling molecules is already being used in the treatment of cancer, but it has lagged behind in the treatment of disorders of the nervous system,” he said. “We think that acting at the level of intracellular signaling represents an alternative treatment approach for neuropsychiatric and neurodegenerative disorders.” • REFERENCES: • Ahmed MR, Berthet A, Bychkov E, et al. Lentiviral overexpression of GRK6 alleviates L-DOPA–induced dyskinesia in experimental Parkinson’s disease. Science Translat Med 2010; 2 (28): 1-9. • Fasano S, Bezard E, D’Antoni A, et al. Inhibition of Ras-guanine nucleotide-releasing factor 1 (RasGRF1) signaling in the striatum reverts motor symptoms associated with L-DOPA–induced dyskinesia. Proc Natl Acad Sci 2010; 107 (50): 21824-29. • Santini E, Heiman M, Greengard P, et al. Inhibition of mTOR signaling in Parkinson’s disease prevents L-DOPA induced dyskinesia. Science Signaling 2009; 2 (80): 1-10. DR. GILBERTO FISONE: “This concept of targeting intracellular signaling molecules is already being used in the treatment of cancer, but it has lagged behind in the treatment of disorders of the nervous system. We think that acting at the level of intracellular signaling represents an alternative treatment approach for neuropsychiatric and neurodegenerative disorders.” Dyskinesia Continued from page 22 If you’ve ever played a role in conducting a federally funded clinical trial, you know that one of the biggest challenges often isn’t the science — it’s the paperwork. Moving a phase 2 exploratory clinical trial forward so that it can answer the necessary questions about a new therapy and — hopefully — lead to testing that therapy in a larger phase 3 trial, nearly always involves cumbersome approval processes that are exponentially multiplied by the number of sites involved in the trial. Have 10 trial sites? That requires 10 institutional review boards (IRBs) and 10 contracts with the NIH that need to be reviewed and reapproved annually. “I have a trial with over 60 sites,” said Merit Cudkowicz, MD, the Julieanne Dorn Professor of Neurology at Harvard Medical School and director of the Neurology Clinical Trials Unit at Massachusetts General Hospital. “It can often take the entire year to get that trial’s contract renegotiated at all 60 sites. And then the next year you have to amend it and do it all over again.” In an effort to turn the cumbersome elephant of today’s phase 2 neuroscience trials into a sleek and effi cient cheetah, the NINDS has recently announced the establishment of an innovative new trials network: NeuroNEXT, a Network for Excellence in Neuroscience Clinical Trials. NINDS will invest more than $84 million over the next seven years in supporting the NeuroNEXT infrastructure, which brings together a group of 25 neuroscience clinical trials sites plus one coordinating center (Massachusetts General) and one data center (the University of Iowa). The aim: to facilitate the rapid, effi cient advancement of phase 2 exploratory trials in neuroscience.