Hunter Syndrome (MPS II)

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 2/3, 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 mg/kg, 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 drug's 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 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 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 2/3, 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 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 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 physician's guidance at the UPMC Children's 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 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.