Rare diseases, while individually uncommon, collectively affect nearly 10% of Americans. The average time to diagnosis for a rare disease patient is five years, with some patients experiencing diagnostic odysseys lasting decades. Researchers at the UC San Diego Sanford Stem Cell Institute are tackling five orphan conditions using precision science, including base editing, organoids, and RNA biology to drive clinical trials and FDA-approved therapies.
Carbamoyl Phosphate Synthetase 1 Urea Cycle Disorder
Children with carbamoyl phosphate synthetase 1 deficiency cannot sufficiently remove nitrogen from their body, leading to excessive ammonia buildup in the blood. Approximately one in every 526,000 to 1.3 million infants worldwide are born with the disorder, which is usually fatal. When infant KJ Muldoon from Pennsylvania was born in 2024, he was lethargic, sleeping excessively, and eating poorly. Doctors confirmed he had CPS1D, a condition that kills half of those born with it within their first week of life. Using a new type of genetic editing called base editing, developed by Alexis Komor, PhD at UC San Diego, clinicians at the University of Pennsylvania and Children’s Hospital of Philadelphia created a bespoke treatment for the critically ill infant. With every infusion, KJ’s condition improved. On June 3, 2025, nearly a year after his birth, KJ was discharged from the hospital for the first time, and in December 2025, he took his first steps.
T-Cell Acute Lymphoblastic Leukemia
This rare leukemia affects around one person per million in the U.S. In 2022, British teen Alyssa Tapley was told she had exhausted treatment options for her T-cell acute lymphoblastic leukemia. Komor’s base editing method offered renewed hope. Three years after being treated with BE-CAR7, a cell-based gene therapy created by Waseem Qasim, PhD at the University College London and Great Ormond Street Hospital, Alyssa was in remission and planning for life beyond high school.
Rett Syndrome
Rett syndrome is a progressive neurodevelopmental disorder typically affecting females, with approximately 5 to 10 out of every 100,000 females diagnosed. Children develop normally until 7 to 18 months, when they begin losing the ability to communicate and move their hands intentionally. Alysson Muotri, PhD, director of the Sanford Integrated Space Stem Cell Orbital Research Center, discovered that insulin-like growth factor 1 helps ease anxiety and breathing issues in females with the condition. His research contributed to trofinetide (Daybue), the first and only FDA-approved treatment for Rett syndrome. Muotri’s research with brain organoids created from skin cells of those with Rett found that antiretrovirals—medications used for HIV—appeared to reduce inflammation and improve functioning. A trial of such drugs in Brazil is currently underway, and the FDA approved a U.S. version of the clinical trial last fall.
Pitt-Hopkins Syndrome and ALS
Pitt-Hopkins syndrome, a rare neurodevelopmental disorder without regression, is diagnosed in around 1,700 patients worldwide so far. In December, the FDA approved a clinical trial of a gene therapy for the syndrome developed by Muotri using brain organoids. It is the first gene therapy discovered using human brain organoids to reach clinical trial. For amyotrophic lateral sclerosis (ALS), which affects around 30,000 Americans at any given time, Gene Yeo, PhD at UC San Diego discovered a key pathway that sets off neurodegeneration in early disease stages. When his team created motor neurons from skin cells of ALS patients and boosted expression of the RNA splicing-associated protein SmD1, motor neurons were spared from degeneration, opening the door to potential therapies that might be repurposed from treatments for spinal muscular atrophy.
This article is an AI-assisted summary. All facts and figures are drawn from the original report: https://today.ucsd.edu/story/from-rett-and-pitt-hopkins-to-als-5-rare-diseases-uc-san-diego-researchers-are-tackling-in-the-lab