The AAV project continues to move forward and we have both progress—and some unexpected developments to report.
The AAV Project originated as the best path towards a viable therapy for children already living with ATP1A3 diseases (e.g.: AHC). It began after more than 6 months of intensive research by our scientific team into therapeutic options. Essentially, the only two real options were drugs and genetic therapies.
We continue to move forward, but also experienced several unanticipated results. In the update below, you’ll see that they turned out to be a blessing in disguise.
On March 10, 2020, Jackson Laboratory (“JAX”) expanded our ATP1A3 mouse colony using IVF. We expected 200 mice to be born, and approximately half of those to harbor a D801N mutation in ATP1A3 and present symptoms of AHC. Here is what occurred:
Because of their error, JAX agreed to pay for both the IVF expansion, and a pilot study on the 26 remaining AHC mice. They injected our mice with one of our AAV vectors and tested them for a rescue at no cost to the project. Even though it delayed the project, we learned an enormous amount.
In the experiments that followed in Jax’s pilot study, mice treated with the therapeutic vector showed:
We are now calibrating the numerous variables at play. Those include identifying the cause of death in our mice, the adequacy of the distribution and expression of our vectors in the mouse brain, potential toxicity of our vectors, the optimal DNA sequence of our vectors (including promoter analysis), specificity of expression of our vectors (expression in the right parts of the brain, and no expression in the wrong parts), dosage testing to make sure we are not over-dosing the mice (overexpression or toxicity), and optimizing the delivery site to make sure that our injections are not injuring the mice and causing additional deaths or seizures.
We see this as very important testing before we initiate the larger, significantly more expensive investigation.
JAX’s error, and their steps to correct it, has allowed us to pause and strengthen the next step – the expensive and extensive round of behavioral tests.
Collaborating scientists have been briefed on our results and have offered substantial input in all areas. Scientists tend to take these course corrections in stride, but all of us as parents feel the delay acutely. To that end, we are currently pursuing these next steps:
The compelling reasons that make AAV-mediated gene therapy such a strong choice for AHC remain. It is a mature, well-tested, highly successful therapy that can be approved by the FDA with relative ease. With a strong plan and this stroke of good luck, the AAV-Project continues to move forward.
For questions about the AAV Project or specific fundraising efforts, please contact Tony Pena (email@example.com), Josh Marszalek (firstname.lastname@example.org) and Simon Frost (email@example.com).
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Alternating Hemiplegia of Childhood Foundation is a 501(c)(3) organization. All contributions are tax deductible.