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Genetic Engineering & Biotechnology News | GENengnews.com | SEPTEMBER 1, 2016 | 39 S cientists at the Martinos Center for Biomedical Imaging at Massachusetts General Hospital (MGH) say they have developed a novel positron emission tomog- raphy (PET) radiotracer that reveals epi- genetic activity within the human brain. In their study ("Insights into Neuroepigenetics through Human Histone Deacetylase PET Imaging"), published in Science Transla- tional Medicine, the investigators report how their radiochemical, called Martinostat, shows the expression levels of important epi- genetics-regulating enzymes in the brains of healthy volunteers. "The ability to image the epigenetic ma- chinery in the human brain can provide a way to begin understanding interactions between genes and the environment," says Jacob Hooker, Ph.D., of the Martinos Cen- ter, senior author of the report. "This could allow us to investigate questions such as why some people genetically predisposed to a disease are protected from it? Why events during early life and adolescence have such a lasting impact on brain health? Is it possible to 'reset' gene expression in the human brain?" Histone deacetylases (HDAC) are impor- tant regulators of gene transcription, and one group of HDACs has been linked to im- portant brain disorders. Several established neuropsychiatric drugs are HDAC inhibi- tors, and others are currently being studied as potential treatment for Alzheimer's disease and Huntington's disease. Martinostat was developed in Dr. Hooker's laboratory and is patterned after known HDAC inhibitors to bind to HDAC molecules tightly in the brain. HDAC Expression Levels PET scans with Martinostat of the brains of eight volunteers revealed characteristic patterns of uptake, reflecting HDAC expres- sion levels that were consistent among all participants. HDAC expression was almost twice as high in gray matter as in white mat- ter. Within gray matter structures, uptake was highest in the hippocampus and amyg- dala and lowest in the putamen and cerebel- lum. Experiments with brain tissues from humans and baboons confirmed Martino- stat's binding to HDAC, and studies with neural progenitor stem cells revealed specific genes regulated by this group of HDACs, many of which are known to be important in brain health and disease. "HDAC dysregulation has been impli- cated in a growing number of brain diseas- es, so being able to study HDAC regulation both in the normal brain and through the progression of disease should help us bet- ter understand disease processes," says Dr. Hooker, who is an associate professor of ra- diology at Harvard Medical School. "We've now started studies of patients with several neurologic or psychiatric disorders, and I believe Martinostat will help us understand the different ways these conditions are man- ifested and provide new insights into poten- tial therapies." n 700 Main St at LabCentral, Cambridge, MA 02139 pilots@fluid-screen.com, +1 203 654 9627 minutes 1440 UNIQUE FEATURES BENEFITS TO PHARMA PILOT OPPORTUNITIES Bacterial detection in just 30 minutes FLUID-SCREEN F L U I D - S C R E E N FLUID-SCREEN F L U I D - S C R E E N Single-use test connected to manufacturing line User interface and data management Bacterial contamination Drug sample Sample: Bioreactor #2 LABEL FREE , no amplification, no growth Results in 30 minutes or less Accurate – over 99% Sensitive – one bacterium Easy to use and portable Differentiates dead and live bacteria Recognizes bacterium type Affordable and disposable for sterility Reduce bioreactor downtime Save time and money Contain contamination & clean-up events Process streamlining and optimization Automated to reduce human error 30min results for slow-growing bacteria Ensure product safety before leaving plant Replace a Petri dish with a microchip and shorten days of bacterial culture into 30 minutes Access to patented technology Product customization Complete bioburden testing solution R&D; collaborations SHIP SAMPLE ANALYZE IN LAB DAYS GROWTH REPORT RESULT COLLECT SAMPLE CURRENT METHOD OUR PRODUCT FLUID-SCREEN F L U I D - S C R E E N FLUID-SCREEN F L U I D - S C R E E N FLUID-SCREEN F L U I D - S C R E E N FLUID-SCREEN F L U I D - S C R E E N 30min 50 TIMES FASTER FLUID-SCREEN F L U I D - S C R E E N pilots@fluid-screen.com www.fluid-screen.com pilots@fluid-screen.com www.fluid-screen.com Replace a Petri dish with a microchip Replace a Petri dish with a microchip Epigenetics Activity Imaged in Human Brain Expression Levels of Important Enzymes Shown for First Time in Craniums of Healthy Volunteers PET scans with Martinostat of the brains of e i g ht h e a l t hy h u m a n vo l u nt e e r s reve a l e d characteristic patterns of uptake, reflecting HDAC expression levels, that were consistent among all participants Getty Images/Yakobchuk