We are pleased to share our latest progress on the AAV gene therapy project. Keeping with our space travel analogy, we are excited to announce that we now have astronauts (mice) for our rocket-ship! We are loading the rocket-ship with supplies and anticipate a launch in January 2020 to start behavior tests to see if we can get a “rescue” of a mouse with AHC using our vectors.
As a reminder, since June 2018, Cure AHC, AHC Foundation and Hope for Annabel have been collaborating on a gene therapy effort using Adeno Associated Virus (AAV) as a system to deliver functioning ATP1A3 to compensate for the mutated ATP1A3 associated with AHC. This project will require many phases or rocket-ship flights with several steps in each phase/flight to hopefully get to a clinical trial by 2022. We are just in the first phase of the AAV Project where we are developing a viral vector and testing its effects in mice.
In our last update in June 2019, we discussed how scientists around the world collaborated to test and improve our vectors, and that we filed patents with the help of law firm Cozen O’Conner to protect the science and try to keep costs of treatment as low as possible for patients and parents. We also shared that we needed to do additional “quality control” testing on bio-distribution and potency of our viral vectors to make sure they are as effective as possible before we test them in mice with AHC.
After some initial problems trying to breed and maintain a colony of mice with AHC, we made some changes to our “astronaut” training program and are now incredibly excited to share that we have three (3) colonies thriving at two different labs. While these colonies will provide us with enough mice for our behavior experiments, the mice are also “open source” meaning that we can share them with other scientists to help promote further research into AHC and treatment options. All of us on the committee will never look at mice the same way again (they are heroes too)!
After repeating tests on our vectors and making modifications, we have a revised batch of vectors ready to be used for this rocket-ship launch. In early 2020, we will inject these vectors into mice with AHC and then conduct behavior tests to see if the symptoms of the mice have improved. Depending upon results, we will know whether the vectors delivering functional ATP1A3 have helped the mice with AHC compensate for their poorly functioning mutated ATP1A3.
In order to best demonstrate the effectiveness of our vectors, we are sharing them with other scientists who can test them in other ways. So, in addition to our work collecting data about the effects of the vectors on our mice with AHC, by collaborating with other scientists we may be able to show how the vectors also impact human stem cell lines. Drs. Kevin Ess (Vanderbilt) and Al George (Northwestern) have agreed to test our vectors on their collection of induced pluripotent stem cells of patients with AHC. This data could be tremendously useful as we move closer to a clinical trial because it will demonstrate the impact on human cells.
While we are very hopeful that our AAV gene therapy delivering functioning ATP1A3 will be effective, we are not content putting all of your fundraising efforts into one rocket-ship. We are working with Dr. Steven Gray (UT Southwestern) to produce and explore “knockdown options” using sequences of RNA and “ASOs” to interfere with, silence and prevent protein expression in specific cells. We were also excited to read in a recent article in the journal Nature about some advances in CRISPR using a technique called “prime editing.” Both these knockdown options and CRISPR prime editing are other forms of “space travel” that may lead to more personal and effective treatment options for AHC in the future.
Another exciting type of “space travel” is a possible genome project where the foundations may be able to help cover the costs for genome testing for any patient who has not yet undergone this testing. We are working to find a lab and scientists to collaborate with us to gather an open-access, anonymized genome database of all our AHC and ATP1A3 patients. By doing whole-genome testing, we hope this will be a catalyst for more research and to help doctors, scientists and families by identifying related diseases, a second causative gene, and modifier genes as potential therapeutic targets. In addition, a genome database may help us develop more precise therapies for our AHC patients and accelerate natural history studies for clinical trials. More details on this project coming soon.
As a community, we need to continue to raise money so that we can fund and control the development of a possible effective AAV gene therapy on our terms to try to ensure access for all families. The more money we raise as a community, the more leverage we have in negotiating terms as we move towards clinical trial by 2022. Families and organizations wanting to support the AAV Project should feel comfortable directing fundraising efforts to one, two or all three of the foundations: Cure AHC, AHC Foundation or Hope for Annabel.
For questions about the AAV Project or specific fundraising efforts, please contact Tony Pena (firstname.lastname@example.org), Josh Marszalek (email@example.com) and Simon Frost (firstname.lastname@example.org).