Mucopolysaccharidosis (MPS)

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 5.01012 or 2.01013 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 therapys 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 the safety, pharmacokinetics, pharmacodynamics, and effectiveness of an investigational drug called GNR-055 in patients with Mucopolysaccharidosis Type II MPS II, also known as Hunter syndrome. This condition is a genetic disorder caused by a deficiency of the enzyme iduronate-2-sulfatase ID2S, leading to harmful buildup of certain substances in cells that affects growth, organs, and the nervous system. The study is a phase 23, multicenter, open-label trial involving different age groups to better understand how GNR-055 works and its safety profile. GNR-055 is a modified enzyme replacement therapy designed to cross the blood-brain barrier, potentially preventing neurological damage and improving quality of life for patients with MPS II. Participants receive weekly intravenous infusions of GNR-055 at doses ranging from 1.0 to 3.0 mgkg, depending on their study group. The study includes multiple cohorts, with adult and pediatric patients receiving specific dosing regimens over the trial period. During the study, participants will undergo various assessments including monitoring of adverse events, urine and serum levels of glycosaminoglycans GAG, cerebrospinal fluid analysis, joint motion measurements, MRI scans of liver, spleen, and brain, heart and lung function tests, neurocognitive evaluations, and biomarker analysis. These evaluations occur at baseline and multiple follow-up visits up to week 56. The study aims to gather detailed data on the drugs impact on disease symptoms, safety, and biological markers to inform future treatment options.

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 12 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 evaluating the efficacy and safety of tividenofusp alfa DNL310, an investigational enzyme-replacement therapy that can penetrate the central nervous system, compared with the standard enzyme replacement treatment idursulfase in children and young adults with mucopolysaccharidosis type II MPS II, which includes neuronopathic and non-neuronopathic forms. This Phase 23, double-blind, randomized, controlled study also allows some participants to enter an open-label treatment phase based on specific criteria. The study includes two main groups Cohort A with participants aged 2 to under 6 years who have neuronopathic MPS II, and Cohort B with participants aged 6 to under 26 years who have non-neuronopathic MPS II. Both tividenofusp alfa and idursulfase are given by repeated intravenous doses. Participants who meet certain criteria may continue treatment in an open-label phase with either DNL310 or idursulfase. Participants will be closely monitored through various assessments during the study, including measurements of cerebrospinal fluid heparan sulfate levels, adaptive behavior scales, developmental tests, walking distance tests, and imaging for liver and spleen volume. Caregiver impressions of change are also collected. The primary outcomes are assessed at 24 and 96 weeks, with additional secondary outcomes measured up to 48 or 96 weeks. The study is designed to last until December 2027, ensuring thorough evaluation of safety and treatment effects.

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 mgkgday divided into three doses, escalating to 18 mgkgday and then 27 mgkgday 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 drugs effects and any side effects in adults with MPS III.

Researchers are evaluating JR-446, a study drug, in patients with Mucopolysaccharidosis type IIIB MPS IIIB, a rare genetic condition. This open-label Phase III trial aims to assess the safety and tolerability of JR-446 while exploring its potential effects in treating MPS IIIB. The study is sponsored by JCR Pharmaceuticals Co., Ltd. and includes children up to 17 years old. Participants will receive JR-446 through intravenous infusion. The study will last up to 4 years with multiple visits during this period to closely monitor patients. The trial does not include a placebo group and does not involve masking or blinding. This long-term study will observe how the drug behaves in the body and evaluate its pharmacodynamic effects. During participation, patients will undergo safety assessments and tests to track the drugs impact, including pharmacokinetic profiling. Researchers will also explore the drugs potential to benefit MPS IIIB symptoms. Visits will include various evaluations and monitoring to ensure participant safety throughout the trial period, which concludes by April 2030.

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 collecting clinical data from patients with various non-malignant disorders undergoing hematopoietic stem cell transplantation HSCT using a reduced-intensity chemotherapy-based regimen. This regimen includes alemtuzumab and other drugs and aims to reduce graft failure and help immune system recovery. The study follows patients with conditions like primary immunodeficiency, inherited metabolic disorders, hereditary anemias, and inflammatory diseases to better understand treatment outcomes. Participants will receive one of three types of stem cell transplants umbilical cord blood, bone marrow, or peripheral blood stem cells. All receive a reduced-intensity conditioning regimen that involves alemtuzumab, melphalan, thiotepa, fludarabine, and hydroxyurea, administered according to the treating physicians guidance at the UPMC Childrens Hospital of Pittsburgh. This observational study gathers medical data without altering standard care. During the study, researchers will monitor outcomes such as the occurrence of acute graft versus host disease GVHD and overall survival for up to five years after transplantation. They will also assess engraftment levels, the timing of immune system recovery, the use of immunosuppressant medications, and donor leukocyte infusions. Medical information will be collected from patients charts after informed consent, with follow-up extending up to five years to evaluate long-term results.

Researchers are investigating a new treatment using ISP-001 in patients with Mucopolysaccharidosis Type I Hurler-Scheie and Scheie syndromes. This Phase 1, first-in-human, open-label, single-arm study aims to evaluate the safety and tolerability of autologous plasmablasts engineered to express alpha-L-iduronidase IDUA through the Sleeping Beauty transposon system. The study focuses on these specific forms of MPS I to assess this novel biological therapy. Participants receive autologous plasmablasts B cells engineered to produce IDUA. Two dose levels are studied 5 x 10e7 cellskg or between 1 x 10e8 and 2 x 10e8 cellskg, both given on Day 0. The treatment involves infusion of these modified cells, and participants are monitored closely afterward. The study does not involve randomization or blinding and includes only one treatment arm. During the study, participants are followed for safety and immune response assessments up to one year. Researchers measure treatment-related adverse events within 24 and 48 weeks, B and T cell populations, IDUA enzyme levels, storage material glycosaminoglycan, circulating antibody levels, and peripheral blood mononuclear cells. Participants must attend follow-up visits and stay close to the study site for at least five days after infusion to ensure safety monitoring. The total duration of participation may extend up to a year or more depending on assessments.