AAV Project Updates

Courtesy of Cure AHC, AHC Kids, and Hope for Annabel

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June 14th, 2019

As we approach the first anniversary of this ground-breaking collaborative effort between Cure AHC, AHC Foundation and Hope for Annabel, 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 a clear target for our rocket-ship!  So, we just need a few more tests before we are ready to load up with supplies and start the countdown for the first rocket-ship flight to test our viral vectors on mice with AHC.  

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 March 2019, we celebrated the incredible fundraising efforts of our global AHC community to help fund this initial phase of developing an effective AAV gene therapy treatment.  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. 

We have a target and modified our supply list:  After repeating tests on our vectors, we now have incredibly important information about how best to use our vectors to get optimal bio-distribution in mice brains.  Based upon this new information, we made some changes to the vector design to also increase potency.  We are still waiting for a few more test results but generally we are seeing positive news about the vectors.  We are in the process of producing new batch of these modified vectors that should be ready to begin testing on mice with AHC in the next 2-3 months.  

We have expanded our crew:  We are fortunate to be working with amazing scientists, universities and research labs around the world.  Since our last update, we expanded our “crew” to include another lab to increase capacity and maintain an aggressive timeline for testing our vectors and performing experiments on mice with AHC.  The scientists and labs have shared information and materials so that we can develop an AHC mouse colony for these experiments as quickly and inexpensively as possible.       

We took steps to ensure a safe and affordable landing: One of our biggest concerns is that if we are able to develop an effective treatment using AAV gene therapy, we want to make sure that the treatment is affordable for all families.  Due to the free legal services donated by the Cozen O’Conner law firm, we were able to file a patent in the US and internationally with ownership assigned to Cure AHC, AHC Foundation and Hope for Annabel to try to protect the intellectual property rights of this collaborative research effort.  By protecting the science, we are in a stronger position to negotiate with industry to keep the cost of any treatment as low as possible.  While we will have filing fees and other costs associated with these patents, we believe that the investment is necessary to make the “landing” or treatment affordable for everyone.  

Although we are ecstatic about the recent development of effective gene therapy treatments for the SMA rare disease community, we also see why it is important to protect our intellectual property rights to avoid the astronomical costs often associated with industry development of treatments for rare diseases.  The new SMA gene therapy treatments cost per patient between $2.1 million for a one-time treatment or $4 million for treatment over 10 years. FDA Approves a Gene Therapy that is the Most Expensive Drug in the World 

Keep supporting our AAV gene therapy mission:  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 AHCAHC Foundation or Hope for Annabel.   


March 5th, 2019

To pick an analogy for this second AAV Project update, we would say that it is like preparing for space travel.  We have the captain and crew, but before we start the countdown we need to make sure our rocket has a clear target, is thoroughly tested, and is fully loaded with fuel and supplies.  

Since June 2018, Cure AHC has lead the charge, collaborating with AHC Foundation and Hope for Annabel 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 with several steps in each phase to eventually get to a clinical trial.  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 on January 20th, we shared that the three foundations had funded over $225,000 of preliminary research and development in preparation for the experiments on mice scheduled to start on April 1st.  We shared that this next step of mice experiments would cost approximately $500,000.  

Our rocket is fueled:  Due to the phenomenal fundraising efforts by families, friends and strangers, we are thrilled to share that the 3 foundations have $436,000 in the bank to dedicate to the next steps of the AAV Project! In addition, our international partners from France, Iceland, Ireland, Netherlands, Spain and the United Kingdom have pledged over $110,000 towards the AAV Project.  We are absolutely in awe of the support of this AAV Project by the AHC community and beyond!  

While we have been able to pool resources to meet and exceed the $500,000 goal for the mouse experiments, please don’t stop your fundraising efforts!  The AAV Project is a multi-phased initiative.  Our gene therapy project is already attractive to industry and institutions who are offering financial support, and the more we can raise as a community the more we can attract the right institutions and the right capital partners.  The goal is to keep our therapy affordable or free for patients and families, and there is much more that we as a community will need to do and fund before we can accomplish that.

Redundancy plans, safety checks, and rocket-supplies:  Our therapy is performing very well in initial experiments, but we have concluded that further testing is necessary before we launch our rocket-ship.  We are determined to proceed carefully and methodically.  Thoroughness is even more important than speed.  

There are still two fundamental questions we need to answer before our rocket has “lift-off”: (1) can our rocket go far enough (biodistribution), and (2) is our payload potent enough (viral potency).  As a result, we are doing another round of quality-control testing, and we are building the same set of viral vectors using a different production technique as a redundancy plan.  To avoid lift-off too early, we need to make sure our therapy will deliver ATP1A3 to the right parts of the brain in exactly the right amounts.  We estimate these additional tests will take approximately three months.  In addition, the development of the mouse colony for experiments is also seeing some delays.  We need the mice to breed quickly to create a large enough colony for our planned tests but breeding mice with AHC is challenging.  The upside is that by doing our additional quality control testing, the mice colony will have time to grow as well.

We want to make sure that the families who have embraced this effort are not disheartened.  Timeline delays are commonplace for meticulous scientists.  We have a rocket-ship that is fully fueled, with a captain and a crew.  Take-off is slightly delayed since we have chosen to implement additional tests.  We feel an intense responsibility to be excellent stewards of your fundraising efforts to ensure we get the best therapeutic results for our kids.   

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 AHCAHC Foundation or Hope for Annabel.