Grant: Operating Grant: Clinical Trials Projects - Indirect Costs

There are over 7000 rare diseases affecting 260-440 million people across the world. This staggering number is almost identical to the number of people afflicted with diabetes worldwide. A large proportion of these rare diseases affect the central nervous system (CNS). In our lab, we focus on developing gene therapy treatments for two rare diseases that directly affect the CNS. These genetically inherited diseases were first described in 1881 by W. Tay, and in 1968 by K. Sandhoff. Today, these diseases are known as Tay-Sachs and Sandhoff disease (TSD and SD, respectively). Children who inherit TSD and SD suffer from progressive and rapid death of brain cells that begins very early in life. This is due to inheritance of gene mutations that cause its encoded protein, beta-HEXA, to lose biological function. Consequently, beta-HEXA fails to carry out its normal biological duty to metabolize a type of brain fat known as GM2 ganglioside. This results in toxic accumulation of unmetabolized GM2 which eventually kills brain cells; and which ultimately, leads to progressive degeneration of overall CNS function. This degeneration is so rapid that children with TSD and SD, die within 5 years of age. Unfortunately, treatments are unavailable for TSD and SD. This motivated a decade-long effort to find a gene therapy-based cure for these diseases. These efforts only recently paid-off with the development of a gene therapy (hB-A) that easily cures TSD and SD in mice. Shortly after in 2021, Health Canada approved hB-A for testing in humans in the first clinical trial for TSD and SD (NCT04798235). Early results proved to be extremely promising; however, the trial was paused due to changing priorities of our sponsor. In this study, we propose to continue testing hB-A on 9 infant participants as part of a new clinical trial. Encouraged by the results of our previous trial, we believe that hB-A has the potential to meet the urgent unmet need to treat children with TSD and SD.