Cures in Sight – Building Momentum for NPHP1 Gene Therapy
Thank You
Thank you for your support of the NPHP1 Family Foundation. With this newsletter, our intent is to periodically share updates with you, so that you can see your support in action and get as excited as we are that cures for NPHP1-associated retinal dystrophy are in sight — and the path to get there is becoming clearer all the time.
As You May Know…
NPHP1 gene mutations and deletions are the most frequent cause of nephronophthisis, which leads to unavoidable kidney failure, often by the early teens. It can be treated with a kidney transplant, after which the condition does not reappear. In the U.S., nephronophthisis occurs in 1 in 922,000 live births.
Of that number, 6-10% of patients will also develop retinal dystrophy, which is a blinding disease of the eye. Having both is extremely rare and falls within a category of conditions termed “diseases of no commercial interest.”
For parents, it’s a triple gut punch: Your child is sick. There is no cure. And there is no interest in developing one. That’s why we exist. We are building a gene therapy to preserve the vision of children and adults impacted by NPHP1 retinal dystrophy. And you are a critical part of that effort.
Why We’re Optimistic
Multiple components of what’s required to build an NPHP1-specific gene therapy already exist.
Gene therapies for the eyes are the most viable routes to treatment, and therapies for other retinal conditions have been approved by the FDA.
NPHP1 is one of only about 100 genes in the body that fit onto the established delivery mechanisms for gene therapies, called AAV vectors.
The regulatory environment is focused on accelerated drug development and approval for rare diseases.
Our partners are incredible.
We just need to put the pieces together, and we will stop this rare, blinding eye disease in its tracks.
Partners in Our Effort
We are heartened by the partners who have enthusiastically joined our effort. Odylia Therapeutics is an innovative, non-profit biotech firm focused on gene therapies for rare diseases of the eye. They are guiding us through the drug development process and have been incredible partners to us.
In parallel, this summer, the National Institutes of Health collected stem cells that will eventually be used to test our therapy. The effort was coordinated by specialized researchers at Stanford University.
Your Support in Action
Establishing Human Cell Lines
In July, we took the first step in our drug development effort. Donated human skin cells were, effectively, “reprogrammed” to behave like retinal cells. Our partners will use these cells in the lab to test how well our therapy works on humans. So cool.
Recovering Cryopreserved Mice
Drug development for rare diseases usually begins by creating a model to replicate the disease in a mouse to test a drug’s efficacy and safety. That process can take years and significant investment.
We are fortunate that there are available mice with NPHP1 retinal dystrophy, and we are in active discussions about recovering them from cryopreservation for testing.
Developing a Patient Community
The largest study of patients with NPHP1 retinal dystrophy included just 16 patients. (One of its authors is an advisor to us.) With his and others’ help, we are building a patient community and collecting data that will inform an eventual natural history study — a key element of the U.S. Food and Drug Administration’s review process.
What’s Next
In our next newsletter we hope to bring you updates on:
Execution Partners
We are receiving proposals now from academic collaborators interested in taking our project forward. These partners would perform the actual mouse and human cell line research, and would put together what’s called a “package” of data to send to the FDA to request to begin a clinical trial. This month, we had fantastic conversations with exceptional researchers and geneticists at top-notch institutions. Any one of them would be fantastic to work with.
Vector Production
Alongside the mouse and cell research, our partners at Odylia will soon begin developing the vector for use in our therapy. The vector is, essentially, the delivery method for gene therapies. Once the vector is designed, we would work with a manufacturing partner to develop enough vector for us to use in testing and in our eventual clinical trial.
FDA Interactions
We have been advised to begin conversations with the FDA as soon as possible, specifically with its Center for Biologics Evaluation and Research (CBER) and its Center for Drug Evaluation and Research (CDER). The reason for this is so that we can get clear expectations, upfront, around what the FDA will want to see in our Investigational New Drug (IND) application. We’re starting those conversations now.
Again, our deepest thanks for your support. If we can answer any questions — or if there’s more you want to see in our next newsletter — please don’t hesitate to get in touch..
