Precision Medicine for improving health care worldwide and treating the untreatable
Modern medicine now understands that among a population of individuals with a given disease there exists considerable variability in the underlying molecular pathophysiology, natural history and in the response to treatment. Personalized medicine refers to the ability to target therapy to an individual based on her or his unique characteristics. Based on an understanding of the heterogeneity between individuals in their disease it is possible to identify the most appropriate and precise treatment for a given individual.
The Levy lab has applied this precision medicine paradigm in two areas of medicine:
First, we have sought to understand why it is that some individuals with Diabetes Mellitus never develop vascular complications such as heart disease or kidney disease. We have identified a common functional polymorphism in the Haptoglobin (Hp) gene which identifies which individuals with Diabetes are at high risk for these complications. Molecular studies done in vitro and in mice transgenic for this polymorphism have demonstrated that this effect is likely due to differences in iron trafficking, antioxidant protection and HDL metabolism. Randomized clinical studies have demonstrated that knowledge of the Hp genotype can improve patient outcomes when coupled with strategies to reduce oxidative stress and hyperglycemia. Ongoing studies are designed to further develop the Hp algorithm in large randomized clinical trials are underway.
Second, we have sought to demonstrate that it is possible to treat autism, intellectual disability and drug resistant epilepsy using precision medicine. We seek to demonstrate proof of concept that a disorder for which there is currently no treatment and which is thought to be untreatable. The studies are based on our discovery of a missense mutation in the gene IQSEC2 in an Israeli child resulting in autism, intellectual disability and drug resistant epilepsy. We are using state of the art CRISPR generated mouse models of the disease and induced pluripotent stem cells from the patient differentiated into neurons to study the pathophysiology of the disease and to use as platforms for drug development.