Shanghai Children's Medical Center Launches World's First Base Editing Clinical Study for Pediatric Chylomicronemia Syndrome

Background

Familial chylomicronemia syndrome (FCS), also known as hyperchylomicronemia, is a rare autosomal recessive genetic disorder. It is caused by biallelic mutations in the lipoprotein lipase (LPL) gene or genes regulating its activity. This leads to severely impaired clearance of chylomicrons, resulting in extremely elevated fasting triglyceride levels, often leading to recurrent acute pancreatitis, abdominal pain and other complications. Current management relies primarily on very low-fat diets, which are difficult to maintain long-term, with limited effectiveness from conventional lipid-lowering drugs.

Shanghai Children's Medical Center has developed a comprehensive system for rare diseases. It established a multidisciplinary team (MDT) clinic for rare and difficult diseases in 1998, founded one of China's first rare disease diagnosis and treatment centers in 2015, led the Shanghai Children's Rare Disease Clinical Research Center in 2020, and built a registry with nearly 10,000 rare disease cases along with specialized databases. The hospital also conducts gene therapy research, including for AADC deficiency.

What was achieved

In January 2026, a team led by Professor Wang Xiumin, director of the Department of Endocrinology, Genetics and Metabolism, and Deputy Director Chang Guoying, launched the world's first clinical study of an in vivo base editing therapy for children and adolescents with FCS. The investigator-initiated trial (IIT) uses CS-121, a lipid nanoparticle (LNP)-delivered base editing drug targeting the APOC3 gene. It is a prospective, single-center, open-label, single-arm study to evaluate safety and efficacy in patients aged 4-18 years with hyperchylomicronemia.

The study is registered as NCT07371767. The hospital's dedicated clinical research ward, which features 26 beds and was built to Phase I standards, supports such trials. In 2025 the ward assisted with more than 30 global multicenter GCP projects and 30 investigator-initiated trials. Subsequent reports noted that the first pediatric patient completed dosing and two-month follow-up with reduced triglyceride levels and no serious adverse events.

How it works

In FCS, defective LPL function prevents breakdown of triglyceride-rich chylomicrons from the diet, causing them to accumulate in the blood. APOC3 is a protein that inhibits LPL and other pathways for clearing these fats. People with natural loss-of-function mutations in APOC3 have lower triglycerides and lower pancreatitis risk without major side effects.

Base editing is a gene-editing technique that uses a modified CRISPR system with a deaminase enzyme to make precise single-letter changes in DNA without creating double-strand breaks. This reduces risks associated with traditional gene editing. In this therapy, LNPs encapsulate the base editor components and are infused intravenously. The particles are taken up primarily by liver cells, where the editor makes a targeted change in the APOC3 gene to reduce or silence its expression, aiming to restore fat clearance and lower triglyceride levels from within the body. The approach is designed as a potential one-time treatment.

What it means for international patients

Shanghai Children's Medical Center operates an International Medical Services Department, established in 2001, which provides services to overseas patients including English language support and multilingual volunteers. The department handles specialist consultations, observation, wards, surgery and well-child checks for international families. It has treated children from countries including Poland, Bulgaria, the United Arab Emirates and Mongolia for conditions such as liver tumors, cerebral palsy and rare diseases.

As this remains an early-phase clinical study with defined inclusion criteria (including age 4-18 years), international patients interested in FCS treatment or participation should contact the hospital's international department directly to confirm current availability, eligibility and enrollment status. The hospital's experience with innovative therapies for rare pediatric conditions may be relevant for families exploring advanced care options.

About the hospital

Shanghai Children's Medical Center is a tertiary pediatric specialty hospital located at 1678 Dongfang Road in Shanghai's Pudong New Area. Affiliated with Shanghai Jiao Tong University School of Medicine, it is designated as a National Children's Medical Center. Founded in 1998, it integrates clinical care, education, research and prevention.

The hospital is known for expertise in congenital heart disease, pediatric hematology and oncology, functional neurosurgery, genetic metabolic disorders and rare diseases. It maintains a dedicated clinical research infrastructure and international medical services unit to support patients from abroad.