Toronto General Research Institute (TGRI)

Nancy F. Olivieri BSc, MD, FRCPC
Senior Scientist
Division of Clinical Investigation & Human Physiology
Toronto General Research Institute (TGRI)

Dr. Olivieri comments on her research interets:

Over the last 5 years, my main contributions can be divided into three major directions within the hemoglobinopathies.

The first research thrust has focused on the in vivo efficacy and toxicity of deferoxamine, the only available treatment for iron overload. With collaborators at Harvard we had provided the first evidence that the incidence of iron-induced cardiac disease in thalassemia major could be reduced with deferoxamine therapy, followed by the first demonstration that iron-induced gonadal dysfunction and abnormalities in sexual maturation in thalassemia could be prevented with deferoxamine.

We then reported the improvement in survival achieved with sustained reduction in body iron with deferoxamine, establishing that the magnitude of the body iron burden is the principal determinant of survival in thalassemia. Recognizing the primary obstacle to survival in these patients as poor compliance with subcutaneous deferoxamine, we designed a novel delivery system of continuous ambulatory intravenous deferoxamine.

In parallel, toxicities of deferoxamine,including severe deferoxamine-associated neurotoxicity, pulmonary and renal toxicity, deferoxamine-induced cartilagenous changes and failure of growth, were extensively characterized.

The second focus, arising out of the first, have focused on the development of new chelating agents as the use of deferoxamine, while lifesaving, is associated with erratic compliance and great expense. In studies of a new orally active iron chelating agent, deferiprone, we defined dose-responses to this agent, reported the first evidence of reduction in tissue iron stores with any orally active iron chelator, and later extensively characterized its toxicity.

The third area of research focus has been the development and evaluation of agents to augment fetal hemoglobin synthesis. This developed from early observations leading to studies to increase fetal hemoglobin synthesis in vitro. We have reported the first hematologic response to arginine butyrate in thalassemia. After observing a promising initial response to the latter, the nominee extended therapy to a larger cohort of patients, demonstrating the complexity of response to this compound.

This information was copied from on August 14, 2006