The Cross-Border Biotech Blog

Biotechnology, Health and Business in Canada, the United States and Worldwide

Friday Science Review: July 8, 2011

Reductive DNA Damage, A New Evil

University of Waterloo ♦ University Health Network ♦ University of Toronto ♦ Published in PNAS, July 5, 2011

The mechanism behind oxidative DNA damage is well known. It has long been thought that oxidative damage causes the majority of DNA damage in a cell, leading to malignant transformation and cancer. New findings suggest that reductive damage is just as bad, if not worse, for the well-being of a cell. Scientists were able to observe ultrafast-electron-transfer reactions between a rare species of electron, known as a prehydrated electron, and different electron scavengers. These measurements are extraordinarily fast, occurring on the femtosecond time scale. When comparing the reductive damage done by electron transfer reactions involving prehydrated electrons, to the oxidative damage done by OH radicals, researchers came upon a rather surprising finding: the yield of reductive DNA strand breaks was roughly twice that of oxidative strand breaks, as measured using gel electrophoresis.

Clinical Study Results: Glutamic Acid Decarboxylase Vaccine in Patients with Type 1 Diabetes

Hospital for Sick Children (and other sites) ♦ Published in Lancet, June 27, 2011

Results from a clinical study run at multiple test centres in both Canada and the USA, indicate that an antigen vaccination targeting glutamic acid decarboxylase (GAD) was unsuccessful in treating type 1 diabetes. Although GAD is a major target of autoimmune response, preclinical data acquired through animal studies failed to translate into an effective treatment in the clinic. The patient group under examination included those 3 – 45 years of age, diagnosed with type 1 diabetes within 100 days. Patients received one of three courses of treatment: (1) three injections of GAD mixed with an adjuvant, (2) two injections of GAD mixed with adjuvant, and one injection of adjuvant alone, or (3) three injections of adjuvant alone.

The primary outcome of the study was the mean area under the curve of serum C-peptide during the first two hours of a meal tolerance test at one year. Patients in the group receiving three doses of the vaccine had a C-peptide value of 0.412 nmol/L at the one year mark, while those receiving three doses of the adjuvant alone had a value of 0.413 nmol/L; the loss of insulin secretion virtually unchanged.

Utilizing the host immune system to attack disease endogenously is a powerful paradigm upon which to build future therapies, but as is so often the case, finding relevant and predictive animal models is a serious limitation in their pursuit.

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