Grant: Project Grant

Creatine (Cr) is an important molecule in cellular metabolism that supports the body's energy requirements, particularly in high energy organs such as the heart, muscles and brain. Cr deficiency can arise due to dysfunctions in the gene (SLC6A8) that encodes a protein called creatine transporter (CT). This Cr deficiency causes a disorder, which is known as CT deficiency (CT-D), and presents with intellectual disability, autism and a wide spectrum of developmental delay/seizures because the levels of Cr in the brain are insufficient to meet energy demands. Currently, there are no treatments available for CT-D, and hence there is a desperate unmet need to find a treatment for it. Our research work to date has led to the development of a gene therapy drug for CT-D, which we call AAV9-hCRT-1. We have established proof-of-concept that this drug can restore Cr levels in the brain and rescue CT-D associated brain abnormalities in mice. The next stage of our work requires include two goals: Goal (a) - Preclinical studies in mice -one study in mice to confirm the safety and therapeutic window of response to drug - called AAV9-hCRT-1 from which we can identify an initial target dose for clinical testing in patients with CT-D; (b) to check distribution of the drug in animals close to humans - non-human primates; and (c) prepare paperwork required to file an application to Health Canada. Completion of these studies will prepare us to attract investors and likely will help commercialize this drug. The drug companies are looking for a advanced programs in which risks have been reduced quite a bit in advance. Moreover, there are incentives in Canada and USA to develop novel drugs for rare diseases. Excitingly, the business market for gene therapy drugs is very encouraging at present and in coming years. We have a strong and capable team to move this project further towards success. This drug may prove to be first effective and long lasting treatment for CT-D.