Wolman Disease

Researchers are evaluating a gene therapy called AAV9-GLB1 for treating Type I and Type II GM1 gangliosidosis, a rare and fatal disorder that destroys nerve cells due to a deficiency in the enzyme beta-galactosidase. This trial aims to test if the gene therapy can help improve symptoms related to these types of GM1 gangliosidosis. The study is a Phase 1/2 non-randomized trial focusing on safety and effectiveness in children ranging from 6 months to 12 years old, sponsored by the National Human Genome Research Institute (NHGRI). Participants will receive a single intravenous infusion of the AAV9-GLB1 gene therapy at doses determined in stages. In Stage 1, different groups of Type I and Type II subjects will receive varying doses to assess safety. Immune system modulation drugs such as rituximab, sirolimus, methylprednisolone, and prednisone will be given before and after gene therapy to reduce immune reactions. Participants will stay at the study site for 8 to 10 weeks initially and may remain for additional safety monitoring after infusion. Stage 2 will administer the dose selected based on Stage 1 data, with further assessments planned. During the study, participants will undergo many tests including blood and urine tests, heart and hearing assessments, ultrasounds, EEGs, lumbar punctures, MRIs, bone scans, IQ and speech tests, and neurological exams. Central line placement and skin biopsies may also be done. Follow-up visits will occur at 3 and 6 months after treatment, then every 6 months for 2 years, and again at 3 years, with yearly visits for 2 more years in an extension study. Researchers will monitor safety, brain development, neurological function, motor skills, and immune responses throughout the study period.

Researchers are conducting a study to systematically screen newborns in the Normandy region for lysosomal storage diseases such as Mucopolysaccharidosis type I and Pompe disease. This observational study aims to evaluate the occurrence and epidemiology of these diseases using dried blood samples collected from newborns. The study is based on previous pilot work and seeks to include about 100,000 newborns over a period of three years. All newborns born in Normandy maternity hospitals who are participating in the national neonatal screening program will have additional blood samples collected on blotting paper for this study. The screening occurs within the first few days after birth, typically from day 2 to day 4. The study will continue until the target number of participants is reached. Participants will have blood samples collected as part of routine neonatal screening, with extra samples taken specifically for this research. The main outcome measured is the number of newborns screened relative to the number of samples collected. Secondary outcomes include the number of positive cases detected for Mucopolysaccharidosis type I and Pompe disease. The study involves parental consent and monitors newborns during these early days, with no further intervention or long-term follow-up described.

Researchers are studying Neutral Lipid Storage Disease (NLSD) and Triglyceride Deposit Cardiomyovasculopathy (TGCV), which are rare diseases with limited information about their symptoms and progression. This study aims to gather worldwide data on when these diseases start, background information about affected patients, and their natural disease course. The study also explores factors that may predict disease outcomes and assesses how well specific treatments work. The study involves creating an international registry to collect information from patients diagnosed with NLSD or TGCV. This registry includes patients with Jordans' anomaly in certain white blood cells, allowing inclusion of various genetic types of NLSD beyond common gene mutations. The study collects both past medical records and ongoing data from patients. Participants will have their health monitored through various tests and evaluations over up to five years. These include blood tests, muscle and heart assessments, biopsies, imaging scans, exercise tests, and surveys of physical function. The main measure is the time from diagnosis to death from any cause. Secondary measures track many health aspects such as muscle strength, heart and liver function, and neurological symptoms. This long-term observation helps researchers understand the disease and treatment effects better.

Researchers are studying the progression of rare genetic neurodegenerative disorders that affect the brain. This research aims to better understand how these diseases develop over time and to analyze the effects of different interventions. The study is observational and focuses on disorders such as MLD, Krabbe Disease, ALD, and many other rare conditions affecting the nervous system. Participants are observed without receiving experimental treatments. The study collects data from patients who are receiving standard care, including those who have undergone Hematopoietic Stem Cell Transplantation (HSCT) and those receiving palliative care. Evaluations by a multidisciplinary team occur regularly: every 3 months during the first year, every 6 months in the second year, and once a year thereafter. During these visits, researchers assess key developmental areas including cognitive, language, gross and fine motor skills, and adaptive living skills over a 15-year period. Brain neurodegeneration is monitored using MRI diffusion tensor imaging in patients from birth to 5 years old, while exploratory biomarkers are also collected. This long-term follow-up helps track disease course and intervention outcomes for up to 15 years.

This research aims to collect detailed, long-term information about patients with Lysosomal Acid Lipase (LAL) Deficiency, a rare genetic disorder caused by a deficiency of the enzyme responsible for breaking down certain fats in the body. The condition can present as a severe and rapidly progressing disease in infants or a more chronic illness in children and adults, affecting the liver, spleen, and lipid levels, and leading to serious health complications including liver damage and cardiovascular risks. The study focuses on understanding the disease's natural history and variability to improve patient care worldwide. This is an observational, multi-center, international disease registry where patients diagnosed with LAL Deficiency, regardless of their treatment status, are followed over time. The registry collects real-world data to evaluate the long-term outcomes and effectiveness of treatments including sebelipase alfa. Participation is voluntary for both patients and physicians, and the study includes patients living with the disease as well as those deceased. Participants contribute data through their regular medical care and follow-up visits, with researchers gathering information about disease progression, treatment responses, and clinical outcomes. The primary goal is to enhance knowledge about LAL Deficiency by monitoring varied patient experiences and health changes over time. The study is ongoing and aims to support clinical practice and regulatory commitments related to sebelipase alfa therapy. The total duration of participation varies based on ongoing data collection.

This research aims to understand the prevalence, diagnostic methods, and clinical features of lysosomal acid lipase deficiency (LAL-D) in children and adolescents considered at risk in the Russian Federation. It is a multicenter real-world observational study focusing on patients aged 12 months to 18 years who have not previously been tested for LAL-D. The study seeks to gather detailed information on how this condition presents and is diagnosed in routine clinical settings. Participants will not receive experimental treatments as this is an observational study. Instead, the study involves identifying patients with signs or symptoms that may suggest LAL-D, such as unexplained liver enlargement, persistent abnormal liver enzyme levels, or specific patterns of cholesterol abnormalities. Researchers will observe and record diagnostic pathways used and clinical characteristics without altering patient care. During the study, participants will undergo evaluations including genetic testing to confirm LAL-D by detecting decreased enzyme activity and specific genetic variants. The primary outcome is to estimate how many patients in the target age group with predefined risk factors have genetically confirmed LAL-D. Assessments will occur around 60 days after enrollment, with data collected on clinical signs, laboratory results, and family history. The study will continue until June 2028, providing insights into this rare condition in pediatric and adolescent populations.

Researchers are evaluating the safety and feasibility of delivering enzyme replacement therapy (ERT) during pregnancy to fetuses diagnosed with Lysosomal Storage Diseases (LSDs). These conditions carry a high risk of serious complications and death around birth, especially when associated with Non-Immune Hydrops Fetalis (NIHF). The study aims to understand if starting ERT before birth can improve outcomes by reducing immune reactions and possibly supporting better brain development during critical periods. The study involves delivering ERT directly into the umbilical vein of the fetus in the womb. The dose depends on the specific LSD and the estimated fetal weight, matching the recommended postnatal weight-based dosing. This treatment is repeated every 2 to 4 weeks, a schedule chosen to balance safety and enzyme activity. This phase 1 trial focuses on determining if fetal enzyme therapy can be safely given and maintained throughout pregnancy. Participants will be pregnant women aged 18 to 50 carrying a fetus diagnosed with one of eight specific LSDs. Researchers will monitor for any treatment-related side effects, the ability to deliver full doses, enzyme activity in urine, and improvements in hydrops if present. Antibody levels against the enzyme will also be checked. The study involves multiple visits over pregnancy and will follow outcomes for up to six years to assess long-term safety and effectiveness.

Researchers are gathering information about patients diagnosed with Lysosomal Storage Diseases (LSDs) to better understand the natural course of these diseases and the results of fetal therapies. The goal is to improve how these conditions are managed before birth and enhance patient care overall. This registry collects both past and current data from individuals diagnosed with various types of LSDs. This study is observational and does not involve any treatments or interventions. It includes patients diagnosed with different lysosomal storage diseases, either before birth or after. The registry aims to collect detailed information on patient outcomes, clinical management, medical decisions, and care quality to help improve healthcare practices for these conditions. Participants will provide data over time, which may include prenatal features, urine tests measuring glycosaminoglycans (GAGs), antibody levels against enzymes, and assessments of heart, growth, movement, and brain functions. The study will track these outcomes up to 15 years, helping researchers understand how these diseases progress and how therapies impact patients. No treatments are given as part of the study, and participation may include sharing medical information and attending periodic evaluations.