Researchers at the University of California San Diego are working to address several rare diseases, which individually affect fewer than 200,000 people in the United States but collectively impact nearly 10% of Americans. Due to limited awareness and diagnostic tools, patients with rare diseases often face long delays before receiving a diagnosis.
“Sometimes hoofbeats are zebras — and we’re working on testing to spot zebras early and find out exactly what kind of zebras they are,” said Catriona Jamieson, M.D., Ph.D., director of the Sanford Stem Cell Institute (SSCI) and professor of medicine at UC San Diego School of Medicine. Her lab focuses on myeloproliferative neoplasms such as primary myelofibrosis, a rare blood cancer that can progress to acute myeloid leukemia. “Each zebra has a unique pattern of stripes.”
The SSCI team conducts research in laboratories, clinical settings, and even in space. Their efforts have led to approved clinical trials and personalized treatments for patients who previously had few or no options.
One condition under study is carbamoyl phosphate synthetase 1 deficiency (CPS1D), a metabolic disorder that prevents infants from removing nitrogen from their bodies, leading to toxic ammonia buildup. This condition is usually fatal within days after birth. In one case from 2024, doctors used base editing—a gene-editing technique developed by Alexis Komor, Ph.D., deputy director of the Sanford Stem Cell Innovation Center—to create a tailored treatment for an infant named KJ Muldoon. The treatment improved his condition significantly; he was discharged nearly a year after birth and began walking later that year.
T-cell acute lymphoblastic leukemia is another rare disease targeted by researchers. It affects about one person per million in the U.S. British teenager Alyssa Tapley received BE-CAR7 cell-based gene therapy using Komor’s base editing method after exhausting other options. Three years post-treatment she remains in remission.
“It’s been very humbling and pretty exciting,” Komor said regarding these cases. “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.”
Rett syndrome primarily affects females who initially develop normally but then lose communication skills and hand control between 7–18 months old. Research by Alysson Muotri, Ph.D.—director of the Sanford Integrated Space Stem Cell Orbital Research Center—helped lead to trofinetide (Daybue), currently the only FDA-approved treatment for Rett syndrome. Muotri also discovered potential benefits from antiretroviral drugs typically used for HIV; clinical trials are underway in Brazil and planned for the U.S.
Pitt-Hopkins syndrome is another neurodevelopmental disorder studied at UC San Diego; it causes intellectual disability and developmental delays among other symptoms. A new gene therapy developed by Muotri’s team became the first such therapy created using human brain organoids to enter clinical trials after recent FDA approval.
“Sometimes there’s just a handful of labs working on a rare disorder, if any,” Muotri said. “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) affects around 30,000 Americans at any given time and leads to progressive loss of motor function due to neuron degeneration. In 2024 Gene Yeo, Ph.D., MBA—director of the Sanford Stem Cell Innovation Center—identified an RNA splicing protein called SmD1 as protective against motor neuron degeneration when expressed at higher levels in cells derived from ALS patients’ skin samples. This discovery could lead existing spinal muscular atrophy treatments being repurposed for ALS.
“We’ve been working more than a decade and a half on ALS,” Yeo said about his laboratory’s research focus. “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, at least from the economic side: to raise the resources necessary to get them to the patients.”
