Innovator Spotlight

Q: What prompted the creation of Jonah's Just Begun (JJB)? What were the challenges in Sanfilippo Syndrome research that JJB felt it could address?
JJB was formed after our 20-month-old son Jonah was diagnosed with Sanfilippo type C. Sanfilippo is a single gene defect disorder and is part of the six mucopolysaccharidosis and one of the many lysosomal storage disorders (LSDs).

In Sanfilippo, the body is missing or lacking an enzyme that breaks down the substrate heparan sulfate (HS). HS is then stored in the lysosome of every cell, causing catastrophic failure leading to death before adulthood. Sanfilippo has four subtypes, designated A to D, depending on which of the four enzymes responsible for breaking down HS is missing or lacking.

After Jonah's diagnosis, my husband I educated ourselves on the science and located scientists interested in helping. From the literature we learned that Sanfilippo type C, unlike the other subtypes, is a membrane bound enzyme, making it harder to treat then the other types. We found that there was no natural history study (NHS), no animal model, no research, no registry, and very few known patients. Type C is the rarest of the four subtypes, occurring in 1 in 1.5 million births, while type A occurs in 1 in 100,000 births.

There are currently several Sanfilippo foundations mainly focused on A and B research. When Jonah was diagnosed, types A and B had mouse models, an ongoing NHS, and upcoming clinical trials.

We realized we had a lot of catching up to do. JJB set out to build our patient population, create a mouse model, and identify treatment options.

Q: Talk about JJB's research strategies and how they overcome the barriers you've identified.
JJB is based out of Brooklyn, NY, and we are surrounded by many renowned hospitals. We were taken under the wing of several influential geneticists, academics, and neurologists well-versed in LSDs. Dr. Wendy Chung at Columbia Presbyterian gave us our marching orders: "Build your patient population, find the academics working in this field, and start your natural history study… By laying the ground work to a clinical trial, pharmaceutical companies will take interest."

Chung offered to hold a patient population meeting for us. A year later our mouse model was created, and we held our first patient population meeting to discuss treatment options. JJB brought together three academics -- Alexey Pshezhetsky, Brian Bigger, and Daniel Greenberg. Maria Escolar, a leading clinician in Sanfilippo, also joined us.

We identified the three most accessible treatment options for Sanfilippo C. We agreed we could try to fix the mutation causing Sanfilippo, try to reintroduce the enzyme back into the body, or lower the level of HS.

Today, three years later, we are making good progress to seeing a treatment for Sanfilippo C. The collaborations formed among our initial principal investigators doubled to include other collaborative scientists. More science continues to unfold with the revelations made from the mouse model. There is now more science going on for Sanfilippo type C than we have funding to keep up with. We have also collaborated with scientists to help them write more grants that are commercially focused to help translate their ideas to products.

Q: JJB has started a biotech company called Phoenix Nest. Why did you take that unusual step for a patient foundation?
Since the founding of JJB, we had accomplished everything we had set out to do. We had our dream team of scientists, active parents, and supportive advisors. Forming Phoenix Nest was the next logical thing to do to commercialize the scientific discoveries we were catalyzing.

We believe we're making steady progress toward a treatment, and there are more possible research projects then we can fund through JJB. The problem with having an ultra-rare single gene defect disease is not the science. Our tiny patient population poses the biggest problem. We are overlooked by pharma and grant reviewers (who see no commercial return on investment or blockbuster drug), and subsequently the disease has not been given adequate support from federal dollars.

Phoenix Nest is a way to tap into additional funding sources through STTR and SBIR grants. Currently we have two STTR grants in review, through collaboration with academic scientists. STTR grants also have higher funding rates than R01 grants.

Creating Phoenix Nest is a practical and preemptive strike; it shows we're serious about getting to treatment. It might sound unusual for many other disease groups. But are they an ultra-rare disease? In the United States a rare disease is defined as one that has 200,000 or fewer patients. Sanfilippo C has about 100 U.S. patients. Treating this disease will have implications for other related diseases; demonstrating this through our strategy may change the way companies view ultra-rare diseases and what is deemed commercially viable.

Q: What do you consider JJB's greatest accomplishments to date?
Our greatest accomplishment is the formation of our consortium HANDS (Helping Advance Neurodegenerative Disease Science), a collaborative consortium made up of advisers, scientists, and Sanfilippo foundations -- JJB and our sister foundations, Sanfilippo Sud, Sanfilippo Barcelona, and JLK-Sanfilippo Research Foundation. Our scientists are the best in the field and are open to collaborations; they have saved each of our foundations valuable time and funding by working together. Their collaborations have made for better science and have opened many doors for novel research. Our advisers play an invaluable role for us. They fill the gap between the scientists and the foundations. When in doubt we can always go to one of our advisors for their expert and impartial advice.

Together we have laid the groundwork for a treatment. We have created a registry, our natural history study is coming together, we have a plethora of basic and applied science ongoing, and this should lead to a treatment in the very near future.

There is something to be said for working in the ultra-rare disease space. There is very little academic competition, so there's no need to work in competitive isolation. Whatever these scientists bring to the clinic or publish will be novel and ground breaking and will hence have high impact. When funded (all or in part) by patient foundations, scientists aren't hampered by competitive funding opportunities that come with a lot of red tape and cyclical funding cycles.

Q: What are top research goals over the next year, and what will it take to reach these goals?
Now that we have laid the foundations for how to treat the disease and have the data to support the concept, our priority will be to find a compound to fit our treatment needs. High-throughput screening for chaperones for Sanfilippo syndrome will be a major focus for us, searching for a specific compound for each type. More assays and animal models will need to be created, and this will require more funding.

The gene therapy program we have funded will be heading to longevity studies this year. The priority will be to balance the funding needs for this and our natural history study and to continue to keep our current projects on track. A lot of time will be required to be spent fundraising this year through grassroots efforts, crowdfunding, and grant writing.

With our upcoming NHS starting to enroll this year, we will need to boost our efforts to find patients who can participate in this study. Finding these patients by promoting our patient registry will be a priority. For that, our HANDS consortium will actively participate in conferences and symposiums related to lysosomal storage diseases, presenting posters, giving talks, using social media, and reaching out to clinicians around the world.