In a recent episode of The Genetics Podcast, Patrick spoke with Dr. Sal Rico, Chief Medical Officer at Encoded Therapeutics. Having worked across small molecules, medical devices, and now gene therapy, Sal has spent the last decade improving treatments for severe neurological conditions, particularly in children.
During the episode, he shares stories from his early career, reflects on the lessons learned from both successful results and heartbreaking challenges in gene therapy, and gives a look behind the scenes at what Encoded is working on now in Dravet and Angelman syndromes.
A winding path to gene therapy
Sal’s journey into drug development started in Mexico, where he initially debated between medicine, law, and computer science. (He jokes that he chose medicine partly to avoid a career staring at screens, which is something he now does daily.) After training in clinical pharmacology in Madrid and Barcelona, Sal worked across therapeutic areas including insomnia, sepsis, infectious disease, and blood safety.
But a turning point came in 2017 when he saw a video of dogs with myotubular myopathy (MTM) responding dramatically to AAV gene therapy. The before-and-after footage was so drastic; dogs that were once immobile were soon walking, then running. The power of genetic medicine was clear, and he knew he had to be part of it.
The highs and lows of XLMTM
Soon after, Sal joined Audentes Therapeutics to lead development of AT132, a gene therapy for XLMTM, a rare, life-limiting muscle disorder. At first, the results were extraordinary: children on ventilators gained strength, met milestones that had never been seen in XLMTM, and in some cases began walking. It was hailed as one of the most promising gene therapies in development.
But a devastating turn followed. In 2020, several patients died due to liver complications, which was something not fully understood at the time. It was a sobering reminder that even in the face of clinical success, gene therapy can carry serious risks. The experience shaped Sal’s thinking going forward; he now places greater emphasis on humility, a deeper understanding of natural history data, and an even stronger focus on patient safety.
What's next at Encoded
At Encoded Therapeutics, Sal is now helping to lead the next generation of precision gene therapies. What sets the company apart is its focus on regulatory elements, non-coding DNA sequences that control when and where genes are expressed. By using proprietary genomics and machine learning tools, Encoded aims to precisely control gene expression in specific cell types. This has big implications for treating neurological conditions where overexpression in the wrong cells could be harmful. Sal is optimistic that, with the right data, they can reduce trial burden, accelerate timelines, and bring treatments to patients faster.
A field built on learning and iteration
Throughout the conversation, Sal says that gene therapy is still in its early chapters. There's enormous promise, but also a lot of roadblocks and difficulties to overcome. Delivery challenges, regulatory uncertainty, and the need for better natural history data are still holding the field back. But learnings from early programs, cross-industry insights, and a growing base of rigorous research are moving things forward.
At the end of the conversation, Sal leaves us with a hopeful message: setbacks are part of the journey, but gene therapy is already changing the way we treat disease. With the right partnerships, clear frameworks, and strong science, that progress can and should reach many more patients in the years ahead.
Listen now:
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