Hurler Syndrome

This research aims to assess the safety, tolerability, and initial effectiveness of JWK008 injection in adults with Mucopolysaccharidosis Type I (MPS I), a rare genetic disorder caused by a deficiency of the IDUA gene enzyme. Current treatments have limitations, particularly in treating effects on the central nervous system. This study investigates a novel gene therapy designed to cross the blood-brain barrier and target liver tissue to deliver therapeutic effects to the brain and body. Participants will receive a single intravenous infusion of JWK008 at one of two doses: 5.0×10^12 or 2.0×10^13 vector genomes per kilogram of body weight. The study uses a dose-escalation design to monitor safety and responses in small groups of participants. This is an open-label trial without a placebo group, focusing on evaluating this gene therapy's effects over time. During the five-year follow-up, researchers will monitor adverse events and measure enzyme activity and glycosaminoglycan levels in blood, urine, and cerebrospinal fluid. Participants will also undergo physical tests like the Six-Minute Walk Test and joint motion assessments, as well as imaging studies to evaluate liver and spleen size. Vector shedding will be tracked to understand how the gene therapy is processed. This long-term monitoring aims to evaluate safety and biological effects comprehensively.

Researchers are evaluating Ambroxol, a drug given in increasing doses, for adult patients with Sanfilippo disease (MPS III). This dose escalation study aims to assess the safety, tolerability, and how the drug behaves in the body over time. The study includes adults aged 18 and older with genetically confirmed MPS III, focusing on important health measures and disease symptoms. Participants will receive Ambroxol orally, either mixed with soft foods or through a feeding tube if needed. The treatment starts with a dose of 9 mg/kg/day divided into three doses, escalating to 18 mg/kg/day and then 27 mg/kg/day at weeks 12 and 24. Each dose increase is followed by assessments including blood and urine tests, heart monitoring, motor skills evaluations, hearing tests, questionnaires, and safety checks conducted both in person and via telemedicine. During the approximately one-year treatment period, participants will undergo multiple visits for health evaluations and drug monitoring. After treatment ends at week 52, a safety follow-up visit occurs four weeks later. Researchers will closely track safety and tolerability, motor function, quality of life, and how Ambroxol is processed in the body. This comprehensive monitoring helps understand the drug's effects and any side effects in adults with MPS III.

Researchers are studying how heart and blood vessel problems develop in people with Mucopolysaccharidosis (MPS), a rare condition affecting the body. They want to understand if people with MPS experience faster changes in their blood vessels and if certain proteins in their blood are linked to these changes. The study also aims to find reliable blood and urine markers to track heart health and guide future treatments. The study includes two groups: people diagnosed with MPS types I or IVA and healthy participants without MPS who have similar age and biological sex. Participants will undergo yearly tests for four years, including carotid ultrasound to image neck blood vessels, echocardiogram to image the heart, blood draws, and urine collection. These tests help track changes in heart and blood vessel structure and function over time. Participants will visit once a year for four years to complete the tests. Researchers will measure heart and carotid artery structure and function, as well as biomarkers in blood and urine at each visit. The study helps monitor heart health changes and may inform future treatment strategies. Participation is open from birth up to 99 years old, and healthy volunteers are included for comparison.

Researchers are evaluating the safety and tolerability of ISP-001, an investigational treatment using genetically engineered B cells, in patients with Mucopolysaccharidosis Type I Hurler-Scheie and Scheie syndromes. This Phase 1, first-in-human, open-label study focuses on using autologous plasmablasts modified to express the enzyme b1-L-iduronidase (IDUA) through the Sleeping Beauty transposon system. The purpose is to assess how well patients tolerate this novel cellular therapy and monitor any related adverse effects. Participants will receive a single infusion of ISP-001 at one of two dose levels: either 5 x 10e7 cells/kg or between 1 x 10e8 and 2 x 10e8 cells/kg on Day 0. The study is non-randomized and involves one treatment group receiving the engineered B cells. After infusion, patients will be monitored closely for safety and treatment impact over several time points, with follow-up evaluations required. During the study, participants will undergo various assessments including monitoring of treatment-related adverse events over 24 and 48 weeks, and immune cell population analyses up to one year. Researchers will also measure IDUA enzyme concentration, storage material levels, circulating antibodies, and perform blood cell analyses. Patients must commit to traveling to the study site for follow-up visits and staying nearby for at least five days after the infusion to ensure proper monitoring. The total study duration for safety and efficacy assessments extends up to one year post-treatment.

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.

Researchers are studying mucopolysaccharidosis (MPS) diseases to better understand their patterns and natural progress. This observational study collects detailed past and ongoing health information from French patients with different types of MPS, including their symptoms, complications, and cognitive development. The goal is to gather comprehensive data to characterize how these diseases affect patients over time. Participants are not given any specific treatment as part of this study. Instead, the study gathers clinical, radiological, electrophysiological, biochemical, and molecular data through regular evaluations. These include growth assessments, imaging tests like bone X-rays and MRI, enzyme activity measurements, and psychomotor and cognitive milestone tracking, collected over an average of five years. During the study, participants will have ongoing clinical evaluations and various tests to monitor their health status and disease progression. The researchers will analyze data on symptoms, complications, and treatment outcomes, including before and during specific therapies if applicable. This long-term follow-up aims to provide detailed insight into MPS diseases and their management, with participation lasting about five years on average.

Researchers are studying Mucopolysaccharidosis VII (MPS VII), also known as Sly Syndrome, to understand how the disease presents and progresses over time. This global, prospective, multicenter, and longitudinal program aims to assess the long-term effectiveness and safety of the treatment vestronidase alfa, including monitoring for hypersensitivity reactions and immune responses. Both treated and untreated patients with MPS VII are included to gather a comprehensive understanding of the disease. The program includes patients receiving vestronidase alfa either through prescription or early access/compassionate use, as well as patients who are untreated or receiving treatments other than vestronidase alfa. This is an observational study without randomization, designed to collect standardized high-quality data from multiple global sites. Treatments are not assigned by the study but observed as part of routine care or compassionate use. Participants will be monitored over a period of 10 years to track the clinical course of MPS VII, the long-term effectiveness of vestronidase alfa, and its safety profile. Data collection includes biomarker analysis, clinical assessments, and patient or caregiver-reported outcomes. The study aims to provide detailed insights into disease heterogeneity and progression by gathering consistent and meaningful data during routine clinical visits.

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.

Researchers are collecting and analyzing clinical information and biological samples from people worldwide who have leukodystrophies, a group of genetic white matter brain disorders. The study aims to improve understanding of these diseases, find new genetic causes, develop biomarkers, and track the natural history of leukodystrophies to support future research and treatment development. This project is one of the largest biorepositories for leukodystrophy patients, with nearly 2,000 participants enrolled over more than ten years. Participants include individuals with suspected or confirmed leukodystrophies or related genetic white matter disorders, as well as healthy controls. The study involves collecting clinical data, standardized assessments, and biological samples to achieve multiple goals, such as defining new patient groups, evaluating next-generation genetic testing, understanding disease mechanisms, and following patients' care and outcomes over time. Consent and assent are required for participation, and participants may be contacted for future studies. During the study, researchers gather clinical information, imaging data, and biological samples to track disease progression and care over a period of up to ten years from enrollment. The main outcome is to identify new homogeneous patient groups with unclassified leukodystrophies. Secondary outcomes include evaluating genetic testing methods, understanding disease biology, and maintaining contact with participants for ongoing research. Participation involves providing data and samples and completing assessments to help advance diagnosis and treatment for leukodystrophy patients globally.