Spotlighting Rare Diseases Research Blog

I began working in the area of rare disease research during the early years of my research training as a PhD student. This work was focused on molecular genetics, disease gene cloning, and genetic diagnosis of several rare disorders of the central nervous system (CNS), including Canavan disease, Hurler syndrome, and Hunter syndrome. I eventually identified the gene mutations that cause Canavan disease and published my findings in Nature Geneticsin 1993. Soon after, I wanted to search for a treatment for Canavan disease and started conducting research on gene therapy, which gradually culminated in a series of discoveries: the identification of a viral vector that can be used for delivering gene therapy to the CNS and treating Canavan disease with intravenous injection; the first preclinical proof-of-concept Canavan disease gene therapy in a mouse model of the disease; and the first-in-human expanded access trial on a patient with Canavan disease. The gene therapy medicine that we developed was licensed to a biopharmaceutical company for formal clinical development in March 2018.

Current Research on Rare Diseases  

My lab continues to conduct research on gene therapy for Canavan disease, as well as on its neurometabolic pathomechanisms.  We are currently also focusing on developing gene therapies for a number of rare genetic conditions that affect neurological functioning (Alexander disease and GM3 synthetase deficiency), metabolic functioning (maple syrup urine disease), and functioning of multiple systems in the body (NGLY1 deficiency).  These projects additionally aim to uncover the molecular pathomechanisms of some of these conditions, including GM3 synthetase deficiency and maple syrup urine disease.   

The Future of Rare Disease Research

I am very optimistic about the effectiveness and safety of gene therapy for monogenetic rare diseases. There are over 7,000 rare diseases, and none are off the table for research and therapeutic development.  Hence, there is always hope for any rare disease, especially when patients participate in research. Their participation provides data that are critical for understanding the molecular pathomechanisms of rare diseases and for evaluating novel therapeutics for safety and efficacy.  My work continues to be inspired by the suffering of rare disease patients and their families, and by my confidence in, and witnessing of, gene therapy‘s effectiveness in treating these diseases.