Rare Disease Day 2023: In conversation with Alex Silver

In support of this year’s Rare Disease Day, the global movement on rare diseases which works towards equity in social opportunity, healthcare, and the provision of diagnostics and therapies for individuals living with rare diseases, we talk to Alex Silver, co-founder of Telaria, Replay’s HSV gene therapy product company targeting rare skin diseases.

After their son Jackson was born and diagnosed with recessive dystrophic epidermolysis bullosa (RDEB), Alex and his wife started a foundation which grew into the EB Research Partnership; the largest global organization dedicated to funding research to treat and cure epidermolysis bullosa (EB).

EB comprises a group of devastating and life-threatening skin disorders affecting children from birth and that makes the skin as delicate as a butterfly's wings. There's currently no cure, so treatments aim to relieve symptoms, reduce pain, and prevent complications, such as infection. The genetic skin disease gene therapy field is advancing research intent on bringing a substantive change to how EB is treated.

You’ve been actively involved in funding and driving research into epidermolysis bullosa (EB) for more than a decade. How has the field changed in that time?

When my fifteen-year-old son was born with recessive dystrophic epidermolysis bullosa (RDEB), there were very few active clinical trials. The disease-modifying trials were highly risky and uncertain in the benefit that could be delivered. Furthermore, gene therapies were much more of a fantasy than a reality. While there is still no disease-modifying therapy approved for EB, the progress over the last 15 years has been tremendous. The number of potential therapies and modalities gives me great hope that a life-changing treatment or potential cure is on the horizon. As the parent of a child living with EB, this can't come fast enough. I am encouraged by the amount of people, companies, and investors working together to create this outcome.

Alex Silver

You established the Epidermolysis Bullosa Research Partnership, which went on to be the largest global organization dedicated to funding research to treat and cure EB. What drove you?

My son has been my motivation since the day he was born. My wife and I were fortunate to have great medical care, but nothing could have prepared us for his diagnosis. After a routine heel prick to test blood sugar because my wife had gestational diabetes, the nurses placed a Band-Aid on his foot that took off all the skin when it was removed. That was the moment that I decided to do whatever I could to help him. We started a non-profit at our kitchen table that I chaired until mid-2022. We grew that from nothing to raising over $55 million, funding over 85 projects and supporting more than 30 clinical trials, mostly via a venture philanthropy model that I created. As my son's condition has advanced – along with my knowledge of how to get commercially sustainable treatments to the finish line – I have reallocated my time towards the most life-changing and commercially viable possibilities out there. I am not alone in saying that as an EB parent, I live in awe of my child's strength, and I am inspired every day by him.

How has the advent of gene therapy changed the EB research field?

Approximately 12 years ago, I was at a leading academic institution that was pioneering a gene therapy for EB. The timeline being discussed was 20+ years out. Yet here we are with gene therapies in or near clinical trial stages! That's amazing. The benefit of gene therapy is that it treats the root cause of the problem. What many people don't realize is that skin is your largest organ, and first line of defense. Everything you do in life impacts your skin – sleeping, waking, and even sitting. In addition, EB really is a connective tissue disorder. The same protein that impacts skin integrity is in your eyes, throat, and GI tract. The people living with EB have a systemic condition. By fixing the gene that causes EB, the therapy should help all the downstream effects of EB such as inflammation, infection, etc. Let's also keep in perspective that there are an estimated 7,000 rare diseases that impact 10% of our population. That is 32-33 million people! Gene therapy is a platform technology. If you can show that it works in EB then you can likely have it work in other rare conditions. In other words, gene therapy success in EB bodes well for the thousands of other rare genetic conditions that exist without treatments.

What are some of the biggest challenges you’ve had to overcome in your EB journey so far?

The greatest challenge for me has been the timeline to an approved life-changing treatment. By that I mean, we established a foundation and drove clinical trials, created a biotech, and advocated for funding in front of the US Senate. I have no doubt that our efforts have helped advance EB therapies and changed the landscape in a positive way. Developing approved, life-changing treatments takes time, and time is something that someone living with a rare disease values the most. I am optimistic though that we are closer to therapies that will really change the lives of those living with EB. When we started our foundation, there were some wonderful supporters, and also some with the view that we couldn't impact the lives of those living with EB because it was too hard to drive change. Looking back now, I can draw a line to almost every single late-stage therapy in clinical trial and our funding of it. That gives me solace, as even if we aren't there yet, we are well on the way.

Given what you know today, compared to when Jackson was born, what advice would you give to a new parent of a child living with EB?

This is a hard question to answer as every child with EB has a unique journey. I think the best advice that I can offer is to try as hard as possible to live in the present and not fantasize about the life that you imagined you would have had as a parent. Nobody believes that his or her child will be born with a rare disease, and there are some very, very hard days. We each have one trip on this earth and, as hard as it has been for my son quite often, I consider myself among the luckiest of people to have him in my life.