Latest news with #CPS1Deficiency
Sky News
16-05-2025
- Health
- Sky News
Baby gets world's first personalised gene therapy treatment
A baby born with a rare genetic disease is "growing and thriving" after getting bespoke gene therapy. It's the first time anyone in the world has been given an experimental gene-editing treatment designed specifically for their disease and took scientists just seven months to develop. Nine-and-a-half-month-old KJ Muldoon, from Clifton Heights, Pennsylvania, has a rare metabolic condition - known as severe carbamoyl phosphate synthetase 1 (CPS1) deficiency - that meant he has spent the first months of his life in a US hospital on a very restrictive diet. In February, however, the boy received the first dose of his bespoke treatment and then follow-up doses in March and April. "We prayed, we talked to people, we gathered information, and we eventually decided that this was the way we were going to go," said KJ's father Kyle Muldoon. KJ has been able to eat more normally and has recovered well from illnesses like colds, which can strain the body and exacerbate his symptoms. He also now takes fewer medications. Some experts estimate severe CPS1 deficiency affects one in a million babies. Those infants lack an enzyme needed to help remove ammonia from the body, so it can build up in their blood and become toxic. "We're still very much in the early stages of understanding what this medication may have done for KJ," said study author Dr Rebecca Ahrens-Nicklas, a gene therapy expert at the Children's Hospital of Philadelphia (CHOP). "But every day, he's showing us signs that he's growing and thriving." Considering how poorly KJ had been, "any time we see even the smallest milestone that he's meeting - like a little wave or rolling over - that's a big moment for us", said his mother Nicole Muldoon. The team behind KJ's treatment, made up of experts from CHOP and the University of Pennsylvania, published the results of their work in the New England Journal of Medicine. Gene therapy Gene therapy is an innovative treatment that aims to cure disease at the source, by editing the DNA causing the problem. The scientists working on KJ's case used CRISPR, the gene editing tool that won its inventors the Nobel Prize in 2020. In KJ's case, the team found the disease-causing mutation in his genes and created the treatment to flip a "letter" in his genetic code to the correct type. "This is the first step towards the use of gene editing therapies to treat a wide variety of rare genetic disorders for which there are currently no definitive medical treatments," said Dr Kiran Musunuru, a University of Pennsylvania gene-editing expert who co-authored the study. The scientists hope that by publishing the results of their treatment quickly, it'll help others to test out similar bespoke treatments. "Once someone comes with a breakthrough like this, it will take no time" for other teams to apply the lessons and move forward, said Carlos Moraes, a neurology professor at the University of Miami who wasn't involved in the study. "There are barriers, but I predict that they are going to be crossed in the next five to 10 years. Then the whole field will move as a block because we're pretty much ready."
Gizmodo
16-05-2025
- Health
- Gizmodo
First-Ever Custom CRISPR Therapy Saves Infant With Deadly Genetic Disorder
A pivotal medical milestone has been reached. For the first time ever, researchers have used a personalized CRISPR-based gene therapy to treat an infant's rare and life-threatening illness. Doctors at the Children's Hospital of Philadelphia (CHOP) and Penn Medicine detailed their achievement in a study published Thursday in the New England Journal of Medicine. The treated child, named KJ, was born with a metabolic disorder known to kill up to 50% of children in their infancy. Now, three months after his first dose, KJ appears to have responded well to the treatment and is doing better than ever. 'Years and years of progress in gene editing and collaboration between researchers and clinicians made this moment possible, and while KJ is just one patient, we hope he is the first of many to benefit from a methodology that can be scaled to fit an individual patient's needs,' said Rebecca Ahrens-Nicklas, director of the Gene Therapy for Inherited Metabolic Disorders Frontier Program at CHOP, in a statement from the hospital. Soon after his birth last summer, KJ was diagnosed with severe carbamoyl phosphate synthetase 1 (CPS1) deficiency. The disorder prevents his liver from producing a key enzyme that breaks down ammonia, a common waste product, into urea (which is then flushed out in urine). Because of this, ammonia levels continue to build up, eventually causing organ damage. While rare, CPS1 can be caused by a variety of different mutations, meaning that cases often don't share the same genetic cause. Certain treatments, including a strict low-protein diet, can help keep ammonia levels down in people with CPS1, but around half of those who develop it as infants die within the first week (cases that emerge later in life have a much higher survival rate). Until now, the only curative treatment available for CPS1 was a liver transplant. But babies like KJ typically have to wait until they're old enough to survive the intensive procedure, during which time they're vulnerable to the severe complications of CPS1, including permanent brain damage. As luck would have it, though, researchers at CHOP and Penn Medicine had been trying to rapidly develop customized gene therapies for people with rare genetic diseases. And KJ seemed like the perfect test case for their emerging approach. With permission from his parents and eventually the Food and Drug Administration, the team set to work. Over the course of just six months, the researchers crafted, tested, and treated KJ with his own personalized gene-editing drug. The therapy uses a form of CRISPR—delivered to his liver cells using lipid nanoparticles—to edit a specific base (bases being the building blocks, or letters, of DNA) in the defective gene responsible for KJ's condition. The goal is to repair the defect and allow his liver to break down ammonia as usual. The therapy was first tested in mice and then monkeys. KJ was initially given a low dose of the gene therapy, codenamed k-abe, in February 2025. After he appeared to tolerate it well, he received two higher doses in March and April with no apparent serious side effects. In the months since, he's been able to ingest increasing amounts of protein and he's required lower doses of another treatment used to manage the condition. He did experience several common childhood infections during this time period, which can be life-threatening in people with CPS1, but he recovered with no major issues—another promising sign. It will take time to know whether the therapy is safe over the long term, however, or if KJ might require additional treatments. But for now, everything seems to be working just as hoped. And KJ's story is ideally only the start. The researchers believe their approach can be tweaked to treat a wide array of ultra-rare genetic diseases. If so, KJ's success might herald a new era of personalized medicine. 'We want each and every patient to have the potential to experience the same results we saw in this first patient, and we hope that other academic investigators will replicate this method for many rare diseases and give many patients a fair shot at living a healthy life,' said Kiran Musunuru, a geneticist at Penn Medicine and lead author of the NEJM paper, in a statement. 'The promise of gene therapy that we've heard about for decades is coming to fruition, and it's going to utterly transform the way we approach medicine.'
Yahoo
16-05-2025
- Health
- Yahoo
US baby receives first-ever customized CRISPR treatment for genetic disease
When you buy through links on our articles, Future and its syndication partners may earn a commission. A baby born with a rare and devastating genetic condition has become the first person ever to be successfully treated with a personalized CRISPR therapy. After receiving three doses of the therapy in the past few months, the infant is now 9.5 months old and thriving, his doctors report. "We want each and every patient to have the potential to experience the same results we saw in this first patient," Dr. Kiran Musunuru, a professor for translational research at the University of Pennsylvania's Perelman School of Medicine, said in a statement. "The promise of gene therapy that we've heard about for decades is coming to fruition, and it's going to utterly transform the way we approach medicine." Musunuru is a co-author of a new paper describing the procedure, which was published Thursday (May 15) in The New England Journal of Medicine. The results were also presented at the American Society of Gene & Cell Therapy's annual meeting in New Orleans this week. The treated child, referred to as KJ, was born with severe carbamoyl phosphate synthetase 1 (CPS1) deficiency. The inherited condition is estimated to affect 1 in 1.3 million people worldwide. It's inherited in an autosomal recessive pattern, meaning a person must inherit two mutant copies of the gene — one from each parent — to develop the condition. Related: CRISPR 'will provide cures for genetic diseases that were incurable before,' says renowned biochemist Virginijus Šikšnys The condition arises from mutations in the CPS1 gene, which codes for a protein the liver uses to process nitrogen compounds in the blood. This nitrogen, generated as the body breaks down proteins, needs to be processed and detoxified into a product called urea to be excreted in urine. But when the CPS1 gene is mutated, the nitrogen-containing compound ammonia builds up in the body and causes damage, especially in the brain. The severity of CPS1 deficiency depends on whether the affected person has complete or partial absence of the gene's encoded protein. Those with a complete lack of the enzyme, like KJ, have the most severe form of the disease. This causes symptoms to show up shortly after birth, including unusual sleepiness, a poorly regulated breathing rate, unwillingness to feed, vomiting after feeding, unusual body movements, seizures or coma. About half of children with this form of the condition die in early infancy. Children who survive to older ages then need to follow a tightly regulated diet, to limit their protein intake, and they may have developmental delays and intellectual disability due to neurological damage. For KJ, symptoms emerged within the first 48 hours of birth. A rapid genetic analysis revealed that both his maternal and paternal copies of the CPS1 gene were shorter than usual, meaning they were "truncating" gene variants. The paternal mutation, called Q335X, had been reported to cause the disease in a previous case. Renal-replacement therapy was used to filter KJ's blood. Later, he was switched to a drug that captured the extra nitrogen in his blood, and he was put on a protein-restricted diet. "Given the severity of his disease, the patient was listed for liver transplantation at 5 months of age," the report notes, but he would have had to grow big enough — and be medically stable enough — to receive one. In the years prior to KJ's birth, Musunuru and Dr. Rebecca Ahrens-Nicklas, director of the Gene Therapy for Inherited Metabolic Disorders Frontier Program at Children's Hospital of Philadelphia, had begun exploring the feasibility of customized gene therapies built using the gene-editing technique known as CRISPR. The two CRISPR-based therapies approved to date have a one-size-fits-all approach: They work by completely disabling a specific gene. But in many genetic disorders, function needs to be restored to a broken gene, and the way that gene is broken differs from patient to patient. One way to address such disorders is through personalized therapies designed to address a patient's unique mutation. The duo had focused on urea cycle disorders, such as CPS1 deficiency, and demonstrated success in animal experiments. When KJ was born, Ahrens-Nicklas approached his parents — Kyle and Nicole Muldoon — with the idea of designing their newborn a custom gene therapy built on their prior work. After discussing the details of the experimental treatment, the Muldoons agreed, Genetic Engineering and Biotechnology News (GEN) reported. The team rapidly developed a customized therapy built upon base editing, which works by changing just one letter in DNA's code. The therapy was designed to fix the Q335X mutation KJ carried, and it was ready to administer within six months of his birth. The infant received his first dose of the therapy in February 2025, at between 6 and 7 months of age, and he received follow-up doses in March and April. These three doses had no serious side effects. KJ can now consume more protein safely and take less of the nitrogen-scavenging drug. He's started sitting up by himself — a sign that he's gaining motor function that may not have been possible otherwise. RELATED STORIES —CRISPR can treat common form of inherited blindness, early data hint —New CRISPR system pauses genes, rather than turning them off permanently —CRISPR used to 'reprogram' cancer cells into healthy muscle in the lab "Seeing him reach milestones that are important for any infant blows us away even more because we know what was stacked up against him from the very beginning," KJ's mother told reporters during a news conference, GEN reported. Although the effects of the treatment have been promising, KJ will need to be carefully monitored for the rest of his life, Ahrens-Nicklas said in the statement. "Although this has been a very specific approach, partly motivated by the devastating nature of the disease, it represents a milestone that demonstrates these therapies are now a reality," Miguel Ángel Moreno-Mateos, a geneticist at Pablo de Olavide University in Seville, Spain, told The Guardian. "As the article reports, the patient will be monitored for a long time to ensure his wellbeing and determine whether additional doses are needed to further improve the symptoms of the disease."
Washington Post
15-05-2025
- Health
- Washington Post
A rare disorder threatened baby KJ. Could a race to edit his genes save him?
On the second day of KJ Muldoon's life, doctors noticed that he was too sleepy. A doctor lifted up his arm. It trembled as it fell back down to his side. A race was on to understand what was wrong. A blood test revealed toxic levels of ammonia building up in KJ's body, threatening to damage his brain — a sign of an ultrarare and severe genetic disorder called carbamoyl-phosphate synthetase 1 (CPS 1) deficiency.
