The mazda pharma Guide 12th August to 18th August 2013 | Page 65

? ? PHARMACEUTICAL ARTICLE antagonist could offer potential benefits in the treatment of disorders such as Alzheimer's disease and in November 2009 Lundbeck initiated the above described 24 week clinical phase II trial with Lu AE58054 as adjunctive therapy in Alzheimer's disease. Alzheimer's disease is a progressive brain disorder in which the brain gradually degenerates. People with Alzheimer's disease develop distressing changes in memory, thought, function and behavior, which worsen over time. These changes increasingly impact the person's daily life and reduce their independence until ultimately these patients are entirely dependent on others. Alzheimer's disease is associated with brain shrinkage and disruptions in the activity of neurotransmitters. The largest development efforts to date on investigational drugs for Alzheimer's have focused on reducing amyloid plaque formation or excessive phosphorylation of tau proteins. The blocking of 5HT6 receptors represents an alternative, potentially promising approach. Alzheimer's disease also has an enormous impact on the patient's caregiver. Most caregivers are close relatives who provide care at home — a demanding and exhausting role that represents a significant emotional and physical burden. Otsuka Pharmaceutical Co., Ltd. is a global healthcare company with the corporate philosophy: 'Otsuka-people creating new products for better health worldwide.' Otsuka researches, develops, manufactures and markets innovative and original products, with a focus on pharmaceutical products for the treatment of diseases and nutraceutical products for the maintenance of everyday health.Lundbeck is a global pharmaceutical company highly committed to improving the quality of life of people living with brain diseases. Proteins involved in immunity potentially cause cancer : A set of proteins involved in the body's natural defenses produces a large number of mutations in human DNA, according to a study led by researchers at the National Institutes of Health. These findings suggest that these naturally produced mutations are just as powerful as known cancer-causing agents in producing tumours. The proteins are part of a group called apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like (APOBEC) cytidine deaminases. The investigators found that APOBEC mutations can outnumber all other mutations in some cancers, accounting for over two-thirds in some bladder, cervical, breast, head and neck, and lung tumors. The scientists published their findings in the journal Nature Genetics. Dmitry Gordenin, Ph.D., is corresponding author of the paper and a senior associate scientist at the National Institute of Environmental Health Sciences (NIEHS), part of NIH said that scientists knew the main functions of APOBEC cytosine deaminases were to inactivate viruses that attack the body and prevent ancient viruses present in the human genome from moving around and causing disrupting mutations. Because they are so important to normal physiology, he and his collaborators were surprised to find a dark side to them — that of mutating human chromosomal DNA. The study is a follow-up to one Gordenin and his group published in Molecular Cell in 2012, after they discovered APOBECs could generate clusters of mutations in some cancers. “The presence of APOBEC clusters in the genome of tumor cells indicates that APOBEC enzymes could also have caused many mutations across the genome," Gordenin said. Gordenin's team at NIEHS, comprised of scientists from the Chromosome Stability Group, headed by Michael Resnick, Ph.D., and the Integrative Bioinformatics Group, headed by David Fargo, Ph.D., took the 2012 research one step further by applying a modern data science approach. The group collaborated with cocorresponding author Gad Getz, Ph.D., and other colleagues from the Broad Institute of MIT and Harvard. They looked for signs of genome-wide APOBEC mutagenesis in cancers listed in The Cancer Genome Atlas, a cancer database funded and managed by the National Cancer Institute and the National Human Genome Research Institute, both part of NIH. Using APOBEC's distinctive DNA mutational signature, they examined approximately 1 million mutations in 2,680 cancer samples, and found that, in some tumours, nearly 70 per cent of mutations in a given specimen resulted from APOBEC mutagenesis. The mutation pattern, which appeared in clusters and individual mutations, could affect many cancer-associated genes. Steven Roberts, Ph.D., a postdoctoral fellow who works with Gordenin, is first author on both studies. He explained that since APOBECs are regulated by the immune system, which is responsive to many environmental factors, he believes there may be a significant environmental component to APOBEC mutagenesis. “We hope that dete ???????????????????????????????????????????????????????????????????????????????t?I???????????%?????????????????????????????????????????????A=  ???????????????????????????????????????????????9%!L??????????????????????????????????????????????????????????????????????????????9% ?9% ???????????????????????????????????????????????????????UL????????????!?????????!????M???????9% ???????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????5?????????????????????????????????Q]??A?????????????%??????????????????????????????????????????????????????????????????????????????????????????????????U?????M???A??????Q???????=???????Q???????????????UL??????????????????????????????????????????????????????????????Q]?????????????????????????????????????Q?????????????????Q]??A??????????????????????????????????????????????????????????????????????????????????%$????????????????????????????????]????????????????????????????????????????????U?????M?????????????????????????????????????????????????????? ????? ? ???????????????Q]??A??????????????5??????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????%????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????Q]?????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????? ??????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????Q]??????????????????????????????????????????????????????????????????????????????????????????????????????Q]????????????????? ????????????????????????????????????????u??????????%5L?!????????????????????????????????????????????????????????????????UL???????????????????????????????????????????????????????????????????????????????????]????!?????=???????????]!