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Archive - Apr 15, 2011

Immunotherapy May Be Helpful in Wiskott-Aldrich Syndrome

In a novel approach that works around the gene defect in Wiskott-Aldrich syndrome, an inherited immune deficiency disorder, researchers used an alternative cell signaling pathway to significantly improve immune function in a 13-year-old boy with the disease. The study, at The Children's Hospital of Philadelphia, provides a proof-of-principle that immunotherapy, which harnesses elements of the body's immune system, may be used to treat this rare but often deadly disorder. "If this encouraging initial result holds up in further clinical studies, we may have a new treatment option for patients with Wiskott-Aldrich syndrome," said pediatric immunologist Dr. Jordan S. Orange, who holds the newly established Jeffrey Modell Endowed Chair in Pediatric Immunology Research at Children's Hospital. The immunotherapy study appears in the April 2011 issue of The Journal of Clinical Investigation. Wiskott-Aldrich syndrome (WAS) is a complex immunodeficiency disorder characterized by recurrent infections, eczema and thrombocytopenia (a low platelet count). Mutations in the WAS gene disable its ability to produce WAS protein (WASp), which crucially affects immune cells—particularly natural killer (NK) cells, a major component of the innate immune system. Without WASp, immune defenses are compromised, leaving WAS patients at risk for premature death from infection and cancers. This risk exists even for patients mildly affected by WAS. The only current cure for WAS is stem cell transplantation, a potentially risky procedure presently justified in severe cases. In addition, Dr. Orange recently contributed to a small experimental study of gene therapy for WAS led by European researchers, which achieved clinical benefits in two severely affected young boys.

NIH Completes Whole-Exome Sequencing of Melanoma

A team led by researchers at the National Institutes of Health is the first to systematically survey the landscape of the melanoma genome, the DNA code of the deadliest form of skin cancer. The researchers have made surprising new discoveries using whole-exome sequencing, an approach that decodes the 1-2 percent of the genome that contains protein-coding genes. The study appears in the April 15, 2011, early online issue of Nature Genetics. Melanoma is the most serious form of skin cancer and its incidence is increasing more quickly than that of any other cancer. A major cause is thought to be overexposure to the sun, particularly ultraviolet radiation, which can damage DNA and lead to cancer-causing genetic changes within skin cells. "It is now clear that genomic analysis will have a major impact on our ability to diagnose and treat cancer," said National Human Genome Research Institute Director Dr. Eric D. Green, who was not involved in the study. "This study represents a collaboration of basic science, clinical research, genome sequencing, and data analysis at its best." The researchers conducted a comprehensive genome analysis and explored the melanoma genome's functional components, especially gene alterations, or mutations. They studied advanced disease — the metastatic stage — when cells have the highest accumulation of gene mutations. "Melanoma is one of the most challenging solid cancers to work with because it has such a high rate of mutation," said senior author Dr. Yardena Samuels, investigator in the Cancer Genetics Branch of the NHGRI's Division of Intramural Research.

Antenna Transcriptome Characterized for Tobacco Hornworm

Insects use their antennae for smelling and thus for locating resources in their environment. Max Planck researchers now present the first complete analysis of genes involved in antennal olfaction of the tobacco hornworm Manduca sexta. Approximately 70 different receptors expressed in some 100 000 neurons allow these moths to detect a large number of odors and to perform odor-guided behaviors. This is the first essentially complete antennal transcriptome characterized in a non-model insect. Insects have a highly sensitive sense of smell. Extremely low concentrations of odor molecules in the air are sufficient to be detected by receptor neurons on their antennae. Specific proteins, so-called receptor proteins, expressed in these neurons recognize the odors. The odor molecules bind to the receptors and produce chemical and electrical signals that are processed in the insect brain and eventually affect the insect's behavior. Apart from the receptors, further proteins involved in olfaction, including enzymes and chemosensory proteins, come into play. Based on these molecular principles, all insects follow their innate and elementary survival formula: finding food, recognizing mates, and − in the case of females − identifying adequate oviposition sites that guarantee nutritious and easily digestible food for their offspring. Moths are popular research objects in addition to fruit flies. The genome of the silkworm Bombyx mori has been fully sequenced; however, this insect has been domesticated by humans for thousands of years, therefore its native conspecifics cannot be found anymore.

New Research Could Lead to Safer, More Effective Trypanosome Treatment

A safer and more effective treatment for 10 million people in developing countries who suffer from infections caused by trypanosome parasites could become a reality thanks to new research from Queen Mary, University of London published in the April 15 issue of the Journal of Biologicasl Chemistry. Scientists have uncovered the mechanisms behind a drug used to treat African sleeping sickness and Chagas disease, infections caused by trypanosome parasites which result in 60,000 deaths each year. The study investigated how the drug nifurtimox works to kill off the trypanosome. Co-author of the study, Dr. Shane Wilkinson from Queen Mary's School of Biological and Chemical Sciences, said: "Hopefully our research will lead to the development of anti-parasitic medicines which have fewer side effects than nifurtimox and are more effective. "What we've found is that an enzyme within the parasites carries out the process nifurtimox needs to be converted to a toxic form. This produces a breakdown product which kills the parasite. "This mechanism overturns the long-held belief that nifurtimox worked against the parasites by inducing oxidative stress in cells." Nifurtimox has been used for more than 40 years to treat Chagas disease (also known as American trypanosomiasis) and has recently been recommended for use as part of a nifurtimox-eflornithine combination therapy for African sleeping sickness (also called human African trypanosomiasis). Dr. Wilkinson and his colleagues Dr. Belinda Hall and Mr. Christopher Bot from Queen Mary's School of Biological and Chemical Sciences focused their research on the characterization of the breakdown product from nifurtimox. "The backbone of nifurtimox contains a chemical group called a nitro linked to a ring structure called a furan," Dr. Wilkinson explained.