Alone, rare diseases are uncommon, each affecting 200,000 people or less in the U.S. Combined, however, they're anything but, affecting nearly 10% of Americans — and posing a significant public health challenge.
Due in part to the way physicians have historically been trained — and the old medical maxim “when you hear hoofbeats, think of horses, not zebras” — the average time to diagnosis for a rare disease patient is five years. For some patients, the journey to diagnosis, known as the “diagnostic odyssey,” lasts decades. Others with ultra-rare disorders may never receive a diagnosis.
Catriona Jamieson, M.D., Ph.D., director of the Sanford Stem Cell Institute and professor of medicine at UC San Diego School of Medicine
“Sometimes hoofbeats are zebras — and we’re working on testing to spot zebras early and find out exactly what kind of zebras they are,” says 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 studies myeloproliferative neoplasms like primary myelofibrosis — a rare blood cancer that can progress to the more aggressive acute myeloid leukemia. “Each zebra has a unique pattern of stripes.”
Researchers at SSCI have taken the fight against rare diseases to the lab, to patients’ bedsides and even to outer space. Their goal: improve the health span — and even lengthen life span — for adults and children with uncommon disorders, for whom treatment options are few or nonexistent. Inspired by their patients, these researchers have seen success, from approved clinical trials in the U.S. and abroad to the creation of bespoke treatments that have saved the lives of children now daring to dream of adulthood.
This Rare Disease Day (February 28, 2026), read on to learn more about five orphan conditions, the people they affect and the researchers fanning the flames of hope for patients around the globe.
Carbamoyl Phosphate Synthetase 1 (CPS) Urea Cycle Disorder
Children with carbamoyl phosphate synthetase 1 deficiency (CPS1D) — a rare inborn error of metabolism — can’t sufficiently remove nitrogen from their body, leading to an excessive build-up of ammonia in the blood. Within mere days of birth, they begin vomiting and refusing food before becoming progressively lethargic and slipping into a coma. Approximately one in every 526,000 to 1.3 million infants worldwide are born with the disorder, which is usually fatal.
Alexis Komor, Ph.D., deputy director of the Sanford Stem Cell Innovation Center and associate professor of chemistry and biochemistry at UC San Diego
When Pennsylvanian KJ Muldoon was born in 2024, it quickly became clear that something wasn’t right. The infant was lethargic, sleeping a lot and eating poorly. Within a couple of days, doctors broke the news to his parents: KJ had CPS1D — a condition that kills half of those born with it within their first week of life.
With no cure available and the clock ticking, KJ’s team of clinicians and scientists at the University of Pennsylvania and the Children’s Hospital of Philadelphia quickly rallied, using a new type of genetic editing called base editing — developed by Alexis Komor, Ph.D., deputy director of the Sanford Stem Cell Innovation Center and associate professor of chemistry and biochemistry at UC San Diego — to create a bespoke treatment for the critically ill infant.
It worked. 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 — the holiday present of a lifetime for his family.
T-Cell Acute Lymphoblastic Leukemia
This rare type of leukemia affects around one person in every million in the U.S., though its prevalence elsewhere depends on where one is in the world. An aggressive blood cancer that often presents suddenly with flu-like symptoms, most patients are alive five years after diagnosis. Around a third, however, relapse within a year or two.
In 2022, doctors told British teen Alyssa Tapley they were out of options to treat her T-cell acute lymphoblastic leukemia. Once again, Komor’s base editing method offered renewed hope. Three years after being treated with BE-CAR7, a cell-based gene therapy utilizing Komor’s method, created by the team of Waseem Qasim, Ph.D., at the University College London and Great Ormond Street Hospital — Alyssa was in remission and planning for life beyond high school — with her eye on cancer research.
Komor credits the success of both KJ and Alyssa’s treatments to their doctors, who understood the biology and severity of their disease; the researchers who developed the treatments using her method; and other professionals who contributed crucial expertise. While Komor has yet to meet either child, she has seen their stories in the news and can’t help but wonder what else she might accomplish for patients without hope.
“It’s been very humbling and pretty exciting,” Komor says. “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 is a progressive neurodevelopmental disorder that typically affects females, though rare male cases have been reported. Those born with the condition — approximately 5 to 10 out of every 100,000 females — develop normally until 7 to 18 months, when they begin to lose the ability to communicate and move their hands intentionally. Children with the disorder develop a lack of muscle coordination, autistic-like behaviors, feeding difficulties, slow growth and seizures.
Alysson Muotri, Ph.D., director of the Sanford Stem Cell Institute Integrated Space Stem Cell Orbital Research Center and professor of pediatrics at UC San Diego School of Medicine
In 2010, Alysson Muotri, Ph.D. — director of the Sanford Integrated Space Stem Cell Orbital Research (ISSCOR) Center and professor of pediatrics at UC San Diego School of Medicine — discovered that, when turned into brain organoids, stem cells created from the skin of people with the syndrome created fewer functional neurons than skin from people without the condition. He later discovered that the hormone insulin-like growth factor 1 helps ease anxiety and breathing issues in females with the condition.
Muotri’s discovery contributed to the development of trofinetide, also known as Daybue — the first and only FDA-approved treatment for Rett syndrome. His research on the syndrome — on the International Space Station, in particular, where cells age more rapidly due to the stress of microgravity and radiation — led to a recent clinical trial of another potential treatment for Rett. Muotri discovered that antiretrovirals — medications used to stop HIV from multiplying in the bodies of those infected with the disease — appeared to reduce inflammation and improve functioning in brain organoids created from the skin cells of those with Rett. A trial of such drugs for Rett syndrome patients is currently underway in Brazil. Last fall, Muotri received FDA approval to launch a U.S. version of the clinical trial as well.
Pitt-Hopkins Syndrome
Like Rett syndrome, Pitt Hopkins syndrome is a rare neurodevelopmental disorder, though it doesn’t involve regression. Children with Pitt-Hopkins — diagnosed in around 1,700 patients worldwide so far — experience intellectual disability, delays in reaching developmental milestones, difficulty speaking, seizures and abnormal breathing patterns.
In December, the FDA approved a clinical trial of a gene therapy for those with the syndrome, developed by Muotri using brain organoids created from the skin cells of those with the disease. It’s the first gene therapy discovered using human brain organoids to reach clinical trial, according to Muotri.
“Sometimes there’s just a handful of labs working on a rare disorder, if any,” Muotri says. “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.”
Gene Yeo, Ph.D., MBA, Sanford Stem Cell Innovation Center Director, who is also professor of cellular and molecular medicine at UC San Diego School of Medicine
Amyotrophic Lateral Sclerosis (ALS)
ALS, also known as Lou Gehrig’s disease, is rare but common enough that you’ve likely heard of it. It affects around 30,000 Americans at any given time — a list that has included celebrities like the late Grey’s Anatomy actor Eric Dane and the late physicist Stephen Hawking. It’s a fatal neurodegenerative disease that destroys neurons in the brain and spinal cord, causing muscle weakness and atrophy, respiratory failure, dementia and paralysis.
In 2024, Sanford Stem Cell Innovation Center Director Gene Yeo, Ph.D., MBA, who is also professor of cellular and molecular medicine at UC San Diego School of Medicine and team discovered a key pathway that sets off neurodegeneration in the early stages of the disease. When his team created motor neurons from the skin cells of patients with ALS, they found that boosting the expression of RNA splicing-associated protein SmD1 spared motor neurons from degeneration — and opened the door to potential therapies. The SmD1 protein is part of a multiprotein complex implicated in spinal muscular atrophy — another rare neurodegenerative disorder, and one for which treatments exist. Such treatments might be repurposed in ALS, halting degeneration after diagnosis, according to Yeo.
“We’ve been working more than a decade and a half on ALS,” Yeo says of his lab. “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.”
