ammonia storm unmasking a suspected rare proximal urea cycle disorder in adulthood

Original title: “Ammonia storm: unmasking a suspected rare proximal urea cycle disorder in adulthood.”

An Ultragenyx gene therapy has scored a win at the midway | An Ultragenyx gene therapy has scored a win at the midway point of its phase 3 trial, successfully reducing ammonia levels in patients with a rare urea cycle disorder. One-time treatment with DTX301 led to 18% lower ammonia levels compared to placebo at 36 weeks, hitting one of the trial's two key endpoints. That gene therapy snub, combined with a pair of phase 3 fails for its brittle bone disease antibody, prompted Ultragenyx to lay off 10% of its workforce last month. Now, the company also has a class-action lawsuit stemming from its communications around the brittle bone disease data to contend with. Ultragenyx urea cycle disorders rare diseases Cell & Gene Therapy Clinical Trial Results clinical trial data Clinical Data Biotech Thirty-six weeks after one-time treatment with the AAV-based gene therapy DTX301, patients’ ammonia levels were 18% lower than placebo, a statistically significant result that met one of the trial’s co-primary endpoints, Ultragenyx reported March 12. After meeting the measure for change in 24-hour plasma ammonia levels, the trial still must meet another primary endpoint—the percent of patients who achieve a response as measured by discontinuation or reduction in baseline disease management. A positive OTC deficiency readout would provide a morale boost for Ultragenyx, as the rare disease specialist has struggled with some setbacks as of late. The company recently resubmitted its application for FDA approval of its Sanfilippo syndrome type A gene therapy, which the agency initially rejected back in July 2025 due to manufacturing concerns.

Original title: “Ultragenyx gene therapy hits co-primary endpoint in phase 3 rare disease study, teeing up potential win”

Observed annually on the last day of February—most recently on February 28, 2026—Rare Disease Day serves as a vital global platform to raise awareness for the Current investigational work includes novel capsids optimized for intravitreal delivery, the use of different promoters to target specific retinal cell types, and dual‑vector strategies aimed at genes too large to fit into a single AAV genome. ... Inborn errors of metabolism are a natural fit for liver‑directed AAV therapy because many disease‑causing enzymes are normally produced in hepatocytes, and relatively modest levels of restored activity can be clinically meaningful. Ongoing trials are exploring AAV therapy for glycogen storage diseases, urea cycle disorders such as ornithine transcarbamylase deficiency, and disorders like phenylketonuria. Neurologic disease has become one of the most intensively targeted categories for AAV gene therapy. Many CNS disorders share three attractive features for this modality: they are often driven by a single gene defect, are relentlessly progressive, and currently lack curative options. As of late 2024–2025, the FDA has licensed multiple AAV vector-based gene therapies across at least six distinct disease areas: inherited retinal dystrophy (RPE65), spinal muscular atrophy (SMA), hemophilia A, hemophilia B, DMD, and AADC deficiency. Notably, some areas now benefit from more than one approved AAV product, such as hemophilia B and SMA (2). Table 1. Recent approved AAV gene therapies. ... Roctavian (valoctocogene roxaparvovec) from BioMarin treats hemophilia A, marked by low factor VIII. It gained EMA approval in 2022 and FDA in 2023 as the first for this disorder. Using AAV5, it carries a working F8 gene for factor VIII to the liver, where cells make the protein.

Original title: “PackGene's Advanced Capabilities in AAV Gene Therapy for Rare Diseases | PackGene Biotech”

Looking ahead, CHOP researchers ... CHOP's Gene Therapy for Inherited Metabolic Disorders (GTIMD) Program. They are studying conditions such as urea cycle disorders, organic acidemias, fatty acid oxidation defects, and phenylketonuria. KJ's case is also spurring discussions about new approval models for personalized therapies, and a New England Journal of Medicine editorial highlighted the lessons it offers the rare-disease ... Looking ahead, CHOP researchers are pursuing causes and treatments for hard-to-treat metabolic disorders through CHOP's Gene Therapy for Inherited Metabolic Disorders (GTIMD) Program. They are studying conditions such as urea cycle disorders, organic acidemias, fatty acid oxidation defects, and phenylketonuria. KJ's case is also spurring discussions about new approval models for personalized therapies, and a New England Journal of Medicine editorial highlighted the lessons it offers the rare-disease community. 25, 2026 /PRNewswire/ -- February 25, 2026 marks one year since KJ, an infant born with severe carbamoyl phosphate synthetase 1 (CPS1) deficiency, became the world's first person to receive a personalized CRISPR-based gene editing therapy. The therapy was developed by physician-scientists at Children's Hospital of Philadelphia (CHOP) and Penn Medicine, and in May 2025, CHOP shared that the treatment – created specifically for KJ's rare disease – was administered safely. Ahrens-Nicklas and Musunuru joined the FDA in announcing a new "plausible mechanism" framework for individualized therapies to speed approvals for rare diseases where large, randomized trials aren't possible. Under the pathway, all variant-specific versions of a gene editor would be treated as one drug, simplifying review. For example, a single trial could enroll people with any of seven urea cycle disorders (from seven different genes) that the same editor can fix, and positive results in as few as 5-10 patients, rather than hundreds, could be enough for FDA approval of the overall platform. We're also working on designing umbrella clinical trials that move us beyond one-patient treatments, accelerating access to scalable, adaptable therapies." Earlier this month, the Muldoon's traveled with KJ to Washington, DC, alongside Ahrens-Nicklas and Musunuru, to share KJ's story with lawmakers. CHOP hosted educational briefing events in collaboration with the Rare Disease Congressional Caucus and the Personalized Medicine Caucus, highlighting the need for sustained federal funding for pediatric research and policies that expand access to personalized gene therapies.

Original title: “Children's Hospital of Philadelphia Marks One-Year Anniversary of World's First Personalized CRISPR Gene Therapy for Child with Rare Genetic Disease”

Looking ahead, CHOP researchers ... CHOP's Gene Therapy for Inherited Metabolic Disorders (GTIMD) Program. They are studying conditions such as urea cycle disorders, organic acidemias, fatty acid oxidation defects, and phenylketonuria. KJ's case is also spurring discussions about new approval models for personalized therapies, and a New England Journal of Medicine editorial highlighted the lessons it offers the rare-disease ... Looking ahead, CHOP researchers are pursuing causes and treatments for hard-to-treat metabolic disorders through CHOP's Gene Therapy for Inherited Metabolic Disorders (GTIMD) Program. They are studying conditions such as urea cycle disorders, organic acidemias, fatty acid oxidation defects, and phenylketonuria. KJ's case is also spurring discussions about new approval models for personalized therapies, and a New England Journal of Medicine editorial highlighted the lessons it offers the rare-disease community. 25, 2026 /PRNewswire/ -- February 25, 2026 marks one year since KJ, an infant born with severe carbamoyl phosphate synthetase 1 (CPS1) deficiency, became the world's first person to receive a personalized CRISPR-based gene editing therapy. The therapy was developed by physician-scientists at Children's Hospital of Philadelphia (CHOP) and Penn Medicine, and in May 2025, CHOP shared that the treatment – created specifically for KJ's rare disease – was administered safely. Ahrens-Nicklas and Musunuru joined the FDA in announcing a new "plausible mechanism" framework for individualized therapies to speed approvals for rare diseases where large, randomized trials aren't possible. Under the pathway, all variant-specific versions of a gene editor would be treated as one drug, simplifying review. For example, a single trial could enroll people with any of seven urea cycle disorders (from seven different genes) that the same editor can fix, and positive results in as few as 5-10 patients, rather than hundreds, could be enough for FDA approval of the overall platform. We're also working on designing umbrella clinical trials that move us beyond one-patient treatments, accelerating access to scalable, adaptable therapies." Earlier this month, the Muldoon's traveled with KJ to Washington, DC, alongside Ahrens-Nicklas and Musunuru, to share KJ's story with lawmakers. CHOP hosted educational briefing events in collaboration with the Rare Disease Congressional Caucus and the Personalized Medicine Caucus, highlighting the need for sustained federal funding for pediatric research and policies that expand access to personalized gene therapies.

Original title: “Children's Hospital of Philadelphia Marks One-Year Anniversary of World's First Personalized CRISPR Gene Therapy for Child with Rare Genetic Disease”