Previous Talents Program Awardees

2010

Dr Renée Bazin, Canada

Dr Renée Bazin is Director of Cell Engineering, Research and Development at Héma-Québec, Canada. She is an Adjunct Professor at the department of Biochemistry and Microbiology, Faculty of Science and Engineering and at the Faculty of Pharmacy, at Laval University (Québec, Canada).

Research proposal: 'Preclinical investigation of intravenous immunoglobulin therapy in the triple transgenic mouse model of Alzheimer's disease' (2 years)

Preliminary clinical studies and epidemiological data suggest that IVIG could be successfully used as passive immunotherapy in Alzheimer's disease (AD). Previous research suggested that the beneficial effect of IVIG was initially associated with the presence of amyloid-beta specific antibodies; however, this was difficult to demonstrate in clinical trials and led to the investigation of an animal model of AD. Dr Bazin and Dr Frédéric Calon (Co-investigator, Associate Professor, Faculty of Pharmacy, Laval University) recently demonstrated that the repetitive infusion of IVIG into the 3xTg-AD mouse model did not elicit a mouse anti-human IgG response, which suggested that 3xTg-AD mice could be used as a model for the preclinical investigation of IVIG therapy of AD.

Dr Bazin and her co-investigator hypothesize that infusion of IVIG to 3xTG-AD mice will induce anti-inflammatory effects leading to a reduction of lesions characteristic of AD, and that use of the 3xTG-AD model will permit to determine the mechanisms and mediators through which IVIG exerts its effects. She expects her research to demonstrate that animals treated with IVIG will show improved cognitive performance along with a significant reduction of neuropathological signs of AD pathology. Furthermore, Dr Bazin hopes that her research project will deliver critical data on the underlying mechanisms of IVIG that are necessary for its clinical application in AD patients on a larger scale.

Dr Alexander R Blackwood, USA

Dr Blackwood is Associate Professor of Pediatric Infectious Diseases at the University of Michigan, USA. He is also the Assistant Director of Pediatric Education and the Director of both the Pediatric Mentoring Program and the Pediatric Resident Scholarly Activity Program.

Research proposal: 'IVIG for the prevention of respiratory exacerbations in ventilator dependent children' (2 years)

Tracheotomized and/or ventilator-dependent children often experience pulmonary exacerbations, particularly during the winter and spring. Exacerbations are often triggered by seasonal viral infections and are accompanied by color and viscosity changes in the secretions, as well as fever and an increased requirement for medical interventions and resources.

Dr Blackwood and his colleagues previously noted that patients who were receiving IVIG replacement therapy for agammaglobulinemia appeared to be protected against serious bacterial and viral infections and had fewer seasonal respiratory illnesses than their immunocompetent companions and family members.

Working on the hypothesis that IVIG may reduce the incidence of seasonal respiratory viral infections, Dr Blackwood and his co-investigators intend to treat 15-20 high-risk patients (1-2 exacerbations in previous two winters) with prophylactic IVIG during the winter (December-April) in order to determine their rates and characteristics of infections in comparison with the respiratory episodes experienced in the previous winters.

Dr Blackwood further intends to examine the mechanism(s) by which IVIG influences the inflammatory response during exacerbations caused by respiratory infections. He hypothesizes that pro-inflammatory cytokines and nitric oxide released in response to viral and secondary infections increase the expression of Toll-like receptors, thereby increasing the susceptibility to secondary infections.

Dr Norman Latov, USA

Dr Normal Latov is Professor of Neurology and Neuroscience and Director of the Peripheral Neuropathy Centre at Weill Medical College of Cornell University in New York, USA.

Research proposal: 'Biomarkers of CIDP in patients with diabetes' (1 year)

Current diagnosis of chronic inflammatory demyelinating polyneuropathy (CIDP) is largely based on clinical presentation and results of electrodiagnostic studies that show evidence for demyelination. However, diabetes can also be associated with mild demyelinating changes, and in patients with both diseases, the presence of demyelination is often ascribed to diabetes rather than CIDP, resulting in under diagnosis.

Previous research by Dr Latov and colleagues identified five genes, all associated with inflammatory processes, that were significantly upregulated in skin of patients with CIDP in comparison to normal subjects and patients with CMT1 or diabetic neuropathy. These results suggested that testing for expression of the five genes in patients with diabetes and suspected CIDP might help distinguish those with CIDP, and provide a biomarker for the diagnosis.

Dr Latov intends to use quantitative PCR analysis to measure the level of expression of the five genes in skin biopsies of patients with diabetic axonal neuropathy, CIDP, or both. He further intends to correlate patients' level of expression with the number, type, and distribution of demyelinating changes in their electrodiagnostic studies. A correlation between upregulation of these genes with the extent of demyelination would support their use as biomarkers for CIDP in patients with diabetes.