Welcome to the CGTA Research Group
Our name stands for “CNS Gene therapy Translation Acceleration.”
Our goal is to bring gene therapies for rare Central Nervous System diseases into clinical trials and use as quickly and efficiently as possible. Our first project is focused on developing a gene therapy for Huntington’s disease.
As noted below, a poster presenting interim results from our on-going research was presented at the 18th Annual Huntington’s Disease Therapeutics Conference in Dubrovnik in April, 2023. The interim results concerned our project investigating the long-term effects of lowering wildtype huntingtin in the brain using shRNA delivered using a viral vector. At the time, the results showed that five out of five animals receiving a huntingtin-lowering vector in the thalamus of the brain had developed motor deficits, while the three animals receiving a control vector had not. As the project has progressed, we now have found that two out of the three animals receiving the control vector later also developed motor deficits. There is a statistically significant difference between the two groups in the severity of their motor deficits (scored on a standardized rating scale by a blinded rater) during the first several months of their in-life period; however, in later months, two of the animals in the control group develop deficits that were just as severe.
Our current working hypothesis is that in addition to whatever effects of huntingtin-lowering are occurring in these animals, there is also a non-specific effect of the AAV6-delivered shRNA, perhaps “mechanistic toxicity” due to the level of shRNA expression, or a delayed immune or inflammatory reaction to the AAV6. We will be continuing our investigation using a lower dose of the AAV vectors (dropping down to a vector load we have found to be innocuous when delivering AAV2-mediated shRNA delivery to the striatum [Grondin et al, 2012]) and we will present further interim results of this long-term study at the next CHDI conference in February. In the meantime, interested parties should be advised that it is premature to make any final conclusions about the safety of lowering wildtype huntingtin in the thalamus based only on our results so far.
We presented interim findings from our study at the 18th Annual CHDI Huntington’s Disease Therapeutics Conference in Dubrovnik, Croatia. See the abstract for poster #1 in the conference materials, or email firstname.lastname@example.org to request details.
We have initiated our main study and now have seven animals in the “in-life” stage of our study plan. Interim results will be presented at upcoming conferences in the spring of 2023.
After unavoidable delays due to the COVID-19 pandemic, we have initiated our study of the safety of long-term huntingtin-lowering in the brain with the delivery of a huntingtin-lowering agent to the thalamus of a pilot animal. The purpose of the pilot is to confirm the activity and the dosage of the agent to be used in the main study that will start later this year.
We have received word from the National Institute of Neurological Disorders and Stroke as follows: “[your] application was reviewed by the National Advisory Neurological Disorders and Stroke Council at its recent meeting. We are pleased to inform you that we anticipate funding this application. Once all pre-award requirements have been met, a notice of grant award will be issued…”
We will provide more details here once this multi-year research project is underway!
Our Huntington’s disease-related grant application to the National Institute of Neurological Disorders and Stroke (NINDS) was reviewed, discussed, and favorably scored by the scientific study section in October, 2019. Here’s hoping the NIH budget is sufficient this year for our score to be within the pay line.
Our grant application to the National Institute of Neurological Disorders and Stroke (NINDS) was received in good order in June, 2019, and will be reviewed by the Chronic Dysfunction and Integrative Neurodegeneration Study Section on October 15, 2019.
We are in the process of preparing a grant application for submission to NINDS, regarding huntingtin-lowering. This application will be responsive to the reviews of our latest application (which received positive reviews, but not a sufficiently good priority score to make the funding cut), and also recent findings about the effects of huntingtin-lowering in animals. See the literature review by Kaemmerer and Grondin, just published this month.