January 2005 Inside this issue... New Research 3-D Structure of Molecule Solved Dyslexia Risk Factor Identified DNA Repair and Prostate Cancer Survival in Parkinson Disease Molecule Important for Fighting Heart Disease Exercise and Fibromyalgia Breaking News TGRI Welcomes New Director New Chair Appointed TWRI/TWH Scientist Honoured Visit us at... UHN's Research Internet Site

New Research Breakthroughs at UHN Finding Will Lead to Targeted Therapies for Heart Disease and Brain Disorders A groundbreaking discovery by OCI/PMH’s Dr. Mitsu Ikura and PhD candidate Ivan Bosanac will lead to the development of new therapies for treating and preventing heart and brain disorders. In collaboration with Dr. Katsuhiko Mikoshiba of the University of Tokyo, Dr. Ikura used special molecular imaging techniques to visualize the IP3 receptor (IP3R) molecule in three-dimensions. Along with its cousin receptor the ryanodine receptor (RyR), the IP3R is responsible for regulating the levels of calcium in our cells—a process that is crucial for many physiological functions including the regulation of our heart beat and brain function. Says Dr. Ikura, “This is a big step towards understanding how the calcium level in the cell is controlled so precisely. The structure of this part of the IP3R is the same in the RyR receptor. Since the IP3R functions in the brain and the RyR functions in the heart, this information could be used to develop drugs for heart problems and brain disorders in the future.” Mol Cell 2005 Jan 21;17(2):193-203. [PubMed abstract] Institute: OCI/PMH Division: Structural & Molecular Biology Risk Factor for Dyslexia Identified Dyslexia is an inherited language-based learning disability and new research by TWRI/TWH’s Dr. Cathy Barr provides evidence that the region containing the gene called EKN1 may be a risk factor for the disorder. Following up on studies by others, Dr. Barr examined the relationship of the EKN1 gene to dyslexia in children aged six to sixteen, who were recruited from 148 families with known reading difficulties. Her genetic analysis revealed that the chromosomal region containing this gene contributes to reading ability and reading-related processes. Says Dr. Barr, “Our findings support the idea that the region of the EKN1 gene may be involved in dyslexia, but further studies are necessary to determine the precise relationship of the gene to the disorder.” Mol Psychiatry. 2004 Dec;9(12):1111-21. [PubMed abstract] Institute: TWRI/TWH Division: Cell & Molecular Biology DNA Repair in Prostate Cancer: When Too Much Isn’t Enough A recent study by OCI/PMH’s Drs. Robert Bristow and Jeremy Squire may have implications for the diagnosis and treatment of prostate cancer. The team compared the levels of expression and function of DNA repair genes in normal and cancerous prostate cells. Despite having a higher expression of DNA repair genes, the cancerous cells acquired a greater number of DNA lesions and chromosome aberrations indicating that certain DNA repair pathways were dysfunctional. Says Dr. Bristow, “Our research shows that the loss of normal DNA repair activity likely plays a role in prostate tumour progression. In the future, we may be able to use this finding to predict how aggressive a tumour is within individual patients and treat their tumours using drugs designed to re-activate DNA repair.” Cancer Res. 2004 Dec 1;64(23):8526-33. [PubMed abstract] Institute: OCI/PMH Divisions: Experimental Therapeutics and Cell & Molecular Biology Study Zeroes in on Predictors of Parkinson Disease Survival A recent study conducted by TWRI/TWH’s Drs. Connie Marras and Anthony Lang, in conjunction with the international Parkinson Study Group, shows that the mortality rate in a large cohort of clinical trial participants with Parkinson disease (PD) is no different than the mortality rate of people in the general population. To examine PD survival in a large group of subjects long-term, the team examined data collected from 800 Parkinson patients who took part in the DATATOP clinical trial starting in 1987. “The data shows that the mortality rate of Parkinson patients who participated in the DATATOP trial does not differ from the general population,” explains Dr. Marras. “It also shows that mortality rates are not different between men and women or between older and younger individuals. It does show though, that mortality is related to the clinical features of PD—specifically the severity of the disease and its rate of worsening, even when observed very early in the disease.” Neurology. 2005 Jan 11;64(1):87-93. [PubMed abstract] Institute: TWRI/TWH Division: Applied & Interventional Research Molecule Critical for Fighting Viral-Induced Heart Disease Myocarditis is an inflammatory disease of the heart muscle that is often caused by infection with a virus called the coxsackievirus. In serious cases, it can lead to heart failure. Previous studies by others indicated that the immune molecule called IFN-beta plays an important role in fighting the virus, and TGRI/TGH’s Drs. Eleanor Fish and Peter Liu further assessed its role by comparing the severity of coxsackievirus infection in mice missing the IFN-beta molecule, to mice with the IFN-beta molecule intact. “Our results clearly show that the viral infection was more aggressive in mice missing IFN-beta,” says Dr. Fish. “The data confirm a critical role for IFN-beta in mediating protection from coxsackievirus infection and subsequent heart problems.” Circulation. 2004 Dec 7;110(23):3540-3. [PubMed abstract] Institute: TGRI/TGH Divisions: Cell & Molecular Biology and Experimental Therapeutics Exercise Eases Symptoms of Musculoskeletal Disease Research by Drs. Sue Gowans, Susan Abbey (TGRI/TGH) and colleagues proves that aerobic exercise can improve physical function, mood, and symptom severity for at least one year following 23 weeks of supervised aerobic exercise in people with fibromyalgia, a disorder that causes widespread musculoskeletal pain and fatigue. Says Dr. Abbey, “The results of our study prove that exercise can improve the symptoms associated with fibromyalgia, and points to the role of exercise in improving quality of life for people with this disorder.” Arthritis Rheum. 2004 Dec 15;51(6):890-8. [PubMed abstract] Institute: TGRI/TGH Division: Behavioural Sciences & Health Breaking News from UHN Research TGRI/TGH Welcomes New Director UHN Research is pleased to announce the appointment of TGRI/TGH’s own Dr. Richard Weisel as the new Director of the Toronto General Research Institute. Dr. Weisel is a cardiovascular surgeon and his major research interests lie in cell transplantation, myocardial protection, and vascular biology. As Director, Dr. Weisel, working with the TGRI Research Council, will help set Research directions at the institute and will help launch integrated initiatives which will support world-leading research programs. OCI/PMH Researcher Awarded Inaugural Chair UHN Research extends its congratulations to Dr. Andrea Bezjak (OCI/PMH) who was awarded the inaugural John and Gail MacNaughton Chair in Thoracic Radiation Oncology. TWRI/TWH Scientist Delivers Award Lecture At the American Academy of Optometry meeting in Florida in December, 2004, Dr. John Flanagan (TWRI/TWH) delivered the Glenn Fry Award Lecture. The award is the highest offered for significant research contributions to the understanding of causes of vision loss.

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