Gaucher Disease

Gaucher disease type 1 GD1 is caused by mutations in the GBA1 gene, leading to a deficiency in the enzyme glucocerebrosidase GCase. This deficiency results in the buildup of glucosylceramide GlcCer in various organs, including the liver, spleen, kidney, bone, lung, and brain, causing cells to change and leading to tissue and organ problems. Researchers are evaluating LY-M001, a gene therapy using an rAAV8 vector, which aims to deliver the GCase protein to liver cells after a single intravenous infusion to address this enzyme deficiency. This clinical trial includes two phases Phase I is a dose escalation study with three dose groups, starting at a lower dose and increasing to higher doses to assess safety. Participants receive a single intravenous infusion of LY-M001 at one of the specified doses. Phase II is a dose expansion study where the recommended dose from Phase I is given to more participants to further evaluate safety and efficacy. The study has a main period of 52 weeks following infusion and a long-term follow-up phase lasting from 53 weeks up to 5 years. Participants will undergo regular assessments including monitoring for adverse events, liver function tests, blood enzyme activity, blood counts, imaging of liver and spleen volumes, bone mineral density, and bone marrow evaluation. Safety evaluations also include electrocardiograms, vital signs, and laboratory tests. The study aims to track the effects of LY-M001 over time, with extended follow-up to gather long-term data on safety and treatment impact throughout the study duration.

Researchers are evaluating LY3884961, a genetic therapy delivered as a single intravenous infusion, in adults with peripheral symptoms of Gaucher Disease. This Phase 12, open-label, multicenter study aims to assess the safety and tolerability of different dose levels of LY3884961. The study includes dose-finding cohorts followed by an expansion cohort to better understand the therapys effects in this patient group. Participants will receive one dose of LY3884961 and will be monitored closely for 18 months to evaluate safety, tolerability, immune response, biomarkers, and treatment effects. The study may include up to three dose levels tested in small groups of patients, with an additional group enrolled afterward. The total study duration for each patient is about five years, including a screening period of up to 60 days. During the trial, participants will have regular evaluations including laboratory tests, imaging, and clinical assessments to track treatment-emergent adverse events and changes in spleen volume, platelet count, and relevant biomarkers. Researchers will also monitor the use and discontinuation of enzyme replacement or substrate reduction therapies. Long-term safety and immune response will be followed for up to 42 months after the initial 18-month period.

Researchers are evaluating the gene therapy FLT201 in adults with Gaucher disease Type 1 who have been on stable enzyme replacement therapy ERT or substrate reduction therapy SRT for at least two years. This Phase 3, non-randomized, multicenter study aims to confirm the efficacy and safety of FLT201 after participants stop their current treatments. FLT201 is an advanced therapy designed to address this rare genetic condition by delivering a gene using a recombinant adeno-associated virus vector. Participants receive a single intravenous infusion of FLT201 during the study. This gene therapy uses a replication-incompetent viral vector to introduce the therapeutic gene. The study includes only one treatment group and does not involve placebo or comparison arms. The primary treatment period focuses on evaluating FLT201s impact over one year after stopping prior therapies. Throughout the study, participants undergo regular assessments to monitor their health and treatment effects. Researchers evaluate the therapys efficacy by measuring clinical outcomes at one year. Safety is closely observed to identify any adverse effects. The total study duration extends to 2032, allowing long-term follow-up of participants responses and overall well-being.

Researchers are studying Gaucher disease to understand its long-term effects, evaluate how well treatments like enzyme replacement therapy ERT and substrate reduction therapy SRT work over time, and identify possible complications. This observational study involves reviewing health records of individuals with all three types of Gaucher disease to gather detailed information. The study is led by Dr. Kishnani at Duke University, a specialist in this condition. Participants health information will be collected systematically from medical records, both from Duke and other treating physicians. The study does not change the usual care patients receive. Researchers will monitor health status at least once a year, depending on when medical information becomes available from treating doctors. The study includes long-term follow-up to observe the course of the disease and treatment outcomes. During the study, researchers will document how Gaucher disease affects various body systems such as the nervous system, liver, and spleen over a period of 10 years. They will also record any adverse events related to ERT or SRT and track long-term complications. Participants will complete surveys and screenings every six months to a year to assess their health and neurological symptoms. This ongoing monitoring helps provide a comprehensive understanding of the diseases progression and treatment effects.

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.

This research aims to evaluate the safety, initial efficacy, pharmacodynamics, immunogenicity, biodistribution, and viral shedding of LY-M001 injection in adult patients with Gaucher Disease Type I. The study is prospective, single-center, open-label, single-arm, and involves a single intravenous dose. The study includes a main phase and a long-term follow-up phase, focusing on adults aged 18 to 60 with confirmed Gaucher Disease Type I. Participants receive a single intravenous infusion of LY-M001 at a dose calculated based on their body weight, administered at a rate of 1 mL per minute. The initial dose group uses 5.0 1012 vgkg, starting with one subject observed for 28 days for safety before enrolling additional subjects. Dose adjustments may be made depending on safety and efficacy data. The study includes a screening period, baseline period, treatment and safety observation period, and a short-term follow-up lasting up to 38 weeks. Those completing the main study or withdrawing early may enter a long-term follow-up lasting up to five years. Throughout the study, participants undergo various assessments including monitoring for treatment-related adverse events and dose-limiting toxicities within 38 weeks post-infusion. Laboratory tests measure glucocerebrosidase protein levels and enzyme activity, as well as glucosylsphingosine in plasma. Participants complete all required evaluations at the end of the study or early withdrawal, and are monitored for safety and efficacy during both short-term and long-term follow-up periods.

Researchers are evaluating the safety, pharmacokinetics, pharmacodynamics, and preliminary effectiveness of an anti-GPRC5D CAR-T cell product called OriCAR-017 in adults with relapsed or refractory multiple myeloma. This Phase III open-label study is the first clinical trial of OriCAR-017 in the United States by OriCell Therapeutics Co., Ltd., aiming to find suitable dosing and assess early treatment results in this patient group. The study includes a Phase I dose escalation stage with three different doses given as a single intravenous infusion to up to 18 participants. This is followed by a dose expansion stage with 10-15 participants and then a Phase II stage that may include up to 48 participants. Each participant receives one infusion of OriCAR-017 to evaluate its effects and safety. Participants will be closely monitored for up to two years after treatment. Researchers will assess the maximum tolerated dose and dose-limiting toxicities within 28 days after infusion. They will also study how the drug moves through and affects the body, measure response duration, progression-free survival, overall survival, and other response rates. Regular evaluations include laboratory tests, clinical assessments, and safety monitoring throughout the study period.

Researchers are studying Gaucher disease, a condition affecting various body systems, focusing on its natural history, clinical outcomes, and biological features in patients receiving standard medical care. The study aims to better understand the disease progression in different types of Gaucher disease, including Type 1 non-neuronopathic, Type 2 acute neuronopathic, and Type 3 chronic neuronopathic. Specific goals include investigating lung and lymphatic involvement in neuronopathic types, refractory skeletal disease, and the overlap between Gaucher disease and Parkinsons disease. Participants are grouped based on disease subtype and symptoms. One group includes patients with neuronopathic Gaucher disease Type 2 or 3 who have lung disease or significant lymph node enlargement. Another includes individuals aged 10 to 75 years with persistent bone disease despite long-term treatment. A third group involves adults with Gaucher disease showing signs of Parkinsons disease. All participants receive standard-of-care therapy, and the study observes their clinical progress over time. During the study, participants undergo evaluations at baseline and at 6, 12, 24, and 36 months. These assessments include measuring lung and lymphatic disease burden, oxygen needs, lung function, bone marrow involvement, bone density, fracture occurrences, neurological symptoms, and Parkinsons-related imaging scores. Blood tests track biomarkers related to inflammation and disease activity. The study also monitors safety and disease progression, providing comprehensive data on Gaucher disease under usual medical treatment over a three-year period.

Type II Gaucher disease is a rare genetic disorder that affects infants, causing severe neurological and visceral problems often leading to death before age two. This trial aims to explore the safety and tolerability of a gene therapy called VGN-R08b, which is designed to address the underlying enzyme deficiency in affected patients. The study is an early-phase, open-label trial conducted at a single center, focusing on infants diagnosed with this condition. VGN-R08b is a gene therapy using an adeno-associated virus AAV9 to deliver a functional copy of the GBA1 gene directly into the brain via intracerebroventricular injection. The study has two parts a dose-escalation phase testing two dose levels with one patient each, followed by a dose-expansion phase including 2 to 4 additional patients. Treatment is given once, and the trial will investigate how well patients tolerate the gene therapy and monitor for side effects. Participants undergo regular assessments including monitoring for adverse events, survival rates up to 24 months of age, and changes in relevant enzyme activity and biomarkers in blood and cerebrospinal fluid over up to five years. The study includes immunogenicity testing and tracking of the gene therapy vector in the blood. Safety follow-up continues long term to assess lasting effects. Parents or guardians provide consent and help with study assessments throughout the participation period.