Clinical OMICS

SEP-OCT 2018

Healthcare magazine for research scientists, labs, pathologists, hospitals, cancer centers, physicians and biopharma companies providing news articles, expert interviews and videos about molecular diagnostics in precision medicine

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14 Clinical OMICs September/October 2018 www.clinicalomics.com States. Rothstein said that he chose the eight clinics that would enroll patients the fastest. Indeed, Answer ALS has been recruiting patients faster than any other trial—on tar- get to recruit 1,000 patients over three years. The fact that Rothstein's research program is moving quickly is not sur- prising, as even his speaking pace indicates that there is no time to be wasted. What led Rothstein to start Answer ALS? He said that medical history taught him a valuable lesson hav- ing "seen one hundred drugs fail." Although there is an ALS mouse model used widely in labs around the world, Rothstein noted that the mouse (although useful) is not equivalent to patients. He recognized that the ALS research world needs reagents that better match their patients. Although human tissue would be ideal, it is not possible to work on human brains. Rarely, a postmortem brain becomes available, but working on non–living tissue is not ideal, either. Generating induced pluripotent stem cells (iPSCs) from ALS patients was the best platform that Rothstein could imagine. How do they do it? The pipeline starts in the clinic and ends with research. First, samples (whole blood, plasma, serum, and cerebrospinal fluid) are taken from enrolled participants. These are sent to the New York Genome Cen- ter where DNA is extracted and sequenced. The blood is then sent to Cedars Sinai Medical Center where cells are reprogrammed into iPSCs and then neurons. They already have 400 lines made and banked, all of which are available (continued from previous page) Might CRISPR-Cas9 Gene Editing Cure Huntington's Disease? Research in the field of Huntington's disease (HD) is light years ahead of the omics-based exploration being done in ALS or Par- kinson's disease. The reason lies in the deep understanding of the genetic mutations that are the cause of HD. In fact, it would be hard to complete an undergraduate genetics course without a good understanding of the genetics behind HD and the biology that underlies it. HD falls into a class of diseases known as trinucleotide repeat diseases, which also encompass roughly a dozen other neurolog- ical diseases, including Fragile X syndrome and Myotonic dystro- phy—a form of muscular dystrophy. These diseases are caused by an expansion of unstable trinucleotide repeats. In the case of HD, three nucleotides, cytosine-adenine-gua- nine (CAG), are repeated in the huntingtin (HTT ) gene. When there are too many repeats, the resulting protein is toxic, and HD is the result. Because HD is caused by a mutant form of the protein huntingtin, if the protein can be blocked, the dis- ease could be halted. Since the mutations are known, and the expression is dominant, CRISPR-Cas9 gene editing may be a potential way to cure the disease. Gary Dunbar, Ph.D., faculty in the Experimental Psychology and Neuroscience Program at Central Michigan University told Clinical OMICs that the most recent research is "looking at ways in which the CRISPR-Cas9 system can specifically target the mu- tated allele, blocking transcription of the mutated protein, and allowing the production of the normal protein." Jong-Min Lee, Ph.D., assis- tant professor of Neurology at Harvard Medical School and Center for Genomic Med- icine noted that "mutant-spe- cific CRISPR strategies are being actively developed for HD." If the editing target is the CAG repeat, "one CRISPR strategy can be applied to all HD patients." Researcers at Genentech, led by Rob Graham, Ph.D., are searching for new genes associated with Parkinson's disease with the aim finding pathways that could be druggable when the patients initially present with symptoms. Jeffrey D. Rothstein, M.D., Ph.D., is director of the Robert Packard Center for ALS Research at Johns Hopkins Medicine, and a driving force behind Answer ALS, which has a goal of comprehensively assessing every aspect of motor neuron function in ALS patients. Rich Riggins for the Robert Packard Center for ALS Research Gary Dunbar, Ph.D., Central Michigan University

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