Morquio Syndrome

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.

This research aims to find genetic causes of unexplained congenital skeletal disorders (GSDs) and better understand their natural development and complications. It is a 5-year project involving collaboration among genetic and bone research institutions. The study focuses on participants with unsolved GSD diagnoses, using advanced genetic testing to identify new gene variants and study their effects in cells and animal models. The goal is to improve diagnosis, knowledge of disease mechanisms, and future treatment strategies for skeletal diseases. Participants include a well-characterized group of 300 individuals with GSD, including 120 with unknown diagnoses. Researchers use whole genome sequencing and RNA sequencing to search for molecular causes. Candidate gene variants are selected with support from clinical findings and large genetic databases. The effects of new variants are studied both in laboratory cells and in transgenic mice to understand their role in disease. During the study, data on the genetic changes, clinical features, and complications of different GSD groups are collected and summarized. The project tracks new gene discoveries and gathers information about the natural course of rare skeletal disorders. This information aims to help develop personalized follow-up and treatment plans. Participation involves genetic sample analysis and clinical data review, with an overall focus on advancing scientific knowledge about skeletal diseases over the 5-year period.

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.

Morquio A disease, also known as Mucopolysaccharidosis IVA (MPS IVA), is a rare genetic disorder causing serious skeletal problems and other health issues like joint laxity, tracheal obstruction, and reduced lung capacity. Researchers are working to better understand how the disease progresses and affects patients of all ages. This study aims to develop non-invasive ways to assess these problems and define clear clinical goals for future treatments. The study involves detailed non-invasive assessments including imaging tests like X-rays, MRI, CT angiography, bone density scans, and gait analysis. It also evaluates lung function, joint mobility, hearing, quality of life, and biochemical markers. These tests will be done at different times over several years to track changes and disease progression without burdening patients. Participants will undergo multiple evaluations at baseline and follow-ups at 18, 36, and 48 months. These include physical measurements, questionnaires, pulmonary tests, imaging scans, and hearing and gait analysis. The study carefully tracks many health aspects to better understand the disease's impact and support the design of future clinical trials and therapies for Morquio A patients.

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 collecting information from individuals diagnosed with various forms of microcephalic primordial dwarfism and related conditions through a registry. The goal is to better understand these rare conditions, identify risk factors, and ultimately improve care and quality of life for those affected. This is an observational study focused on gathering data from medical records without additional procedures or visits. The study involves reviewing existing medical records, including specialist evaluations, surgical reports, blood and urine test results, genetic testing, and imaging such as x-rays, CT, MRI, or MRA scans. No new tests or clinic visits are required for participation. All data is collected and stored solely from the participant's medical history. Participants will not be required to attend any study visits or undergo special testing. The research team will analyze the collected information to characterize the natural history of these forms of primordial dwarfism over a period of five years. The study is designed to be minimally invasive, relying entirely on existing medical information without impacting the participant's routine care.

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.