Rare diseases affect fewer than 200,000 people individually in the United States, but together they impact nearly 10% of Americans. This presents a significant public health challenge due to difficulties in diagnosis and limited treatment options.
Catriona Jamieson, M.D., Ph.D., director of the Sanford Stem Cell Institute (SSCI) at UC San Diego School of Medicine, commented on the complexity of diagnosing rare diseases: “Sometimes hoofbeats are zebras — and we’re working on testing to spot zebras early and find out exactly what kind of zebras they are. Each zebra has a unique pattern of stripes.”
Researchers at SSCI have expanded their work from laboratory research to clinical applications and even space-based studies. Their aim is to improve health outcomes for adults and children with rare disorders, many of whom lack effective treatments. Some efforts have led to approved clinical trials and personalized therapies that have improved or saved lives.
Carbamoyl phosphate synthetase 1 deficiency (CPS1D) is one such rare metabolic disorder affecting newborns. Without adequate removal of nitrogen from the body, infants develop dangerous levels of ammonia soon after birth. The condition can be fatal within days if untreated. In 2024, a child named KJ Muldoon was diagnosed with CPS1D shortly after birth. A team from the University of Pennsylvania and Children’s Hospital of Philadelphia used base editing—a genetic technique developed by Alexis Komor, Ph.D., deputy director at Sanford Stem Cell Innovation Center—to create a custom treatment for KJ. Following several infusions, KJ’s health improved significantly; he left the hospital almost a year later and took his first steps in December 2025.
Another case involved Alyssa Tapley, a British teenager diagnosed with T-cell acute lymphoblastic leukemia—a rare form affecting about one person per million in the U.S. After exhausting standard treatments in 2022, Alyssa received BE-CAR7 therapy based on Komor’s gene-editing method through work led by Waseem Qasim, Ph.D., at University College London and Great Ormond Street Hospital. Three years post-treatment, she remains in remission.
Komor reflected on these cases: “It’s been very humbling and pretty exciting,” she said. “I’m fairly early in my career. These kids are really motivating me to get up every morning and keep up the work, to see what else I can do.”
Research into Rett syndrome—a progressive neurodevelopmental disorder mostly affecting females—has also seen progress at UC San Diego. Alysson Muotri, Ph.D., director of the Sanford Integrated Space Stem Cell Orbital Research (ISSCOR) Center, discovered that stem cells from patients created fewer functional neurons when turned into brain organoids compared to those without the condition. His findings contributed to developing trofinetide (Daybue), currently the only FDA-approved treatment for Rett syndrome.
Muotri’s research extended to experiments aboard the International Space Station where rapid cell aging under microgravity provided further insights into potential treatments using antiretroviral drugs originally designed for HIV therapy. Clinical trials based on these findings are ongoing in Brazil; Muotri recently secured FDA approval for a similar trial in the U.S.
Pitt-Hopkins syndrome is another neurodevelopmental disorder studied by Muotri’s team. Affecting around 1,700 people globally so far, it leads to intellectual disabilities without regression as seen in Rett syndrome patients. In December 2025, an FDA-approved clinical trial began for gene therapy developed using brain organoids derived from patient skin cells—the first such trial according to Muotri.
“Sometimes there’s just a handful of labs working on a rare disorder, if any,” said Muotri. “I like to give hope to rare disease patients, to let them know there are people who want to study their conditions, that they’re not alone.”
Amyotrophic lateral sclerosis (ALS), while still considered rare—with approximately 30,000 affected Americans—is better known due partly to high-profile cases such as physicist Stephen Hawking and actor Eric Dane (CDC ALS facts). Gene Yeo, Ph.D., MBA—director at Sanford Stem Cell Innovation Center—identified pathways triggering neurodegeneration early in ALS by studying motor neurons generated from patient skin cells (Yeo Lab information). His team found that increasing expression of SmD1 protein protected these neurons; since related proteins play roles in spinal muscular atrophy (for which treatments exist), this discovery may allow repurposing existing drugs for ALS patients.
“We’ve been working more than a decade and a half on ALS,” Yeo stated regarding his lab’s long-term commitment. “Over the last six or seven years we’ve spent a lot of time building next-generation therapeutics for ALS. The next stage is the most difficult…to raise resources necessary to get them to patients.”
