Issue link: http://www.e-digitaleditions.com/i/164496
S H E D Q UI ON IS AI G CH L T US B MEET THE COMPOUND VITAL SIGNS NAME: PF-02545920 CHEMICAL FORMULA: C25H20N4O MOLECULAR MASS: 392.452 g/mol TYPE OF COMPOUND: PDE10A Inhibitor MECHANISMS OF ACTION: PDE10A inhibition increases the activity of both the cAMP and cGMP signaling cascades, as well as the MAP kinase pathway, and results in a powerful induction of striatal gene transcription and an overall increase in striatal output. PF-02545920 Pfizer, cont... PAPAPETROPOULOS: By combining ICM's expertise with our medicinal chemistry and clinical experience, we are hoping to directly translate the circuitry level data acquired in our preclinical trials into HD patients. We are also looking at safety, because this will be the first time that our PDE10A inhibitor, or any PDE10A inhibitor, will be administered to HD patients. Details about the study are listed at www.clinicaltrials.gov6.The design of the study was presented at the recent CHDI meeting in Venice, and there is a lot of enthusiasm at Pfizer for this study. HD INSIGHTS: It sounds like you're doing lots of novel things in this trial. The first is that you're investigating a novel class of compounds for HD. And the second is that you're including some novel techniques to measure connectivity, including functional MRI. I don't believe fMRI has been used before as a technique in HD clinical trials. PAPAPETROPOULOS: That is correct. This is our attempt to humanize clinical research and look at circuits rather than symptoms. We believe that circuits are more preserved than behaviors, so they are easier to translate. And when we see congruency between human clinical patients and animal models, our confidence increases. The question remains whether a signal in the circuit will translate into a clinical patient benefit, but that is still to be addressed in future trials. HD INSIGHTS: Dr. Zaleska, Dr. Papapetropoulos, thank you for your contributions to HD research and for taking the time to share them with HD INSIGHTS. Spyros Papapetropoulos, MD, PhD, is a neurologist and movement disorder specialist trained at the National Hospital for Neurology and Neurosurgery, Queen Square, London UK, who leads Pfizer's HD clinical program. He holds an academic appointment with the University of Miami Miller School of Medicine. He has spent his entire academic career studying movement disorders, and since transitioning to industry, he has focused on migraine and pain, neurodegeneration, and neurorehabilitation. When Dr. Papapetropoulos is not working to develop drugs for HD, he focuses on medications for Parkinson disease. He is also an avid tennis player. Margaret Zaleska, PhD is a neuroscientist who leads the PDE10 inhibitor for HD research project in the Pfizer Neuroscience division. She earned her PhD in Biochemistry at the Polish Academy of Science in Warsaw, Poland, and then completed post-doctoral programs focused on neuroscience research at SUNY in the Department of Pharmacology and Experimental Therapeutics, and at the Oklahoma Medical Research Foundation. She was a member of the research faculty of the Perelman School of Medicine at the University of Pennsylvania, then joined Wyeth Research's Neuroscience Division in Princeton, NJ in 1993. When Pfizer acquired Wyeth in 2009, Dr. Zaleska became a member of the Pfizer Neuroscience team. In her spare time, Dr. Zaleska enjoys exploring Pfizer Neuroscience's new hometown of Cambridge, Massachusetts. HD Insights, Vol. 5 Copyright © Huntington Study Group 2013. All rights reserved. 7