Tay-Sachs Disease

Researchers are studying the natural history and progression of gangliosidosis diseases, including Tay-Sachs disease, Sandhoff disease, and GM1 gangliosidosis. The study aims to develop quantitative methods to understand how these diseases evolve and vary among patients. This information will be important for evaluating future treatments like gene therapy, guiding medical decisions, measuring treatment outcomes, and informing families about potential disease outcomes. The study includes two main parts. The first part follows infants and juveniles with these diseases to observe how their condition changes over time. The second part focuses on adults with late-onset Tay-Sachs disease, using brain imaging and cognitive tests to study nervous system changes. Participants will be observed over multiple years to collect detailed data on their disease progression. Participants will undergo neuropsychological tests, brain MRIs, enzyme activity measurements, genetic testing, and clinical assessments at enrollment and then at 12, 24, 36, 48, and 60 months. The study collects detailed information on brain structure, cognitive status, and biochemical markers to track disease changes. This observational study lasts several years, with ongoing monitoring to better understand these rare conditions and support future treatment development.

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 long-term safety, tolerability, pharmacokinetics, biomarkers, and clinical effects of daily Nizubaglustat (AZ-3102) in patients with GM2 gangliosidosis or Niemann-Pick Type C (NPC) disease. This open-label phase 2 study includes two groups: patients continuing from a previous phase 2 study (RAINBOW), and NPC patients transitioning from stable, full-dose Miglustat treatment after at least 12 months. The study aims to understand safety and disease impact with this new treatment approach. Participants in both cohorts receive daily oral Nizubaglustat tablets. Cohort 1 includes patients who previously participated in the RAINBOW study and continue treatment, while Cohort 2 consists of NPC patients aged 12 or older who have received Miglustat but experienced stable or worsening disease and now switch to Nizubaglustat. The study does not involve a placebo group and is open-label. During the average 4-year study period, participants undergo regular assessments including monitoring of adverse events, electrocardiograms, seizure frequency, and blood tests for drug levels and biomarkers related to disease activity. Researchers evaluate changes in specific substances in the blood linked to GM2 gangliosidosis and NPC disease. Participants are expected to complete all treatment and evaluation visits as scheduled to help assess the long-term effects and safety of Nizubaglustat.

Researchers are evaluating the safety and effects of oral nizubaglustat (AZ-3102) in children and young individuals aged 4 years and older diagnosed with late-infantile or juvenile forms of Niemann-Pick type C disease, GM1 gangliosidosis, or GM2 gangliosidosis. This Phase 3, double-blind, randomized, placebo-controlled, multicenter trial uses a Master Protocol Research Program to study these rare diseases in separate subprotocols. Participants are randomly assigned in a 2:1 ratio to receive either oral nizubaglustat tablets or a matching placebo. The study includes two main subprotocols based on disease type: one for Niemann-Pick type C disease and another for GM1 or GM2 gangliosidosis. Each subprotocol may have specific procedures and eligibility requirements that are detailed separately. During the 18-month trial, participants will be monitored for safety and efficacy outcomes related to their specific disease. Researchers will collect information on how many participants are assigned to each subprotocol from the baseline through month 18. The trial is quadruple-masked, meaning patients, caregivers, investigators, and those assessing outcomes will not know the treatment assignments. The overall participation duration is 18 months, allowing for thorough observation and evaluation.

Researchers are exploring how the stress of caregiving affects the health and well-being of adults who care for people with chronic medical conditions. This observational study aims to understand the social, psychological, behavioral, and biological factors involved in caregiving over time, including during and after the death of the care recipient. The study includes caregivers of various chronic conditions such as inherited metabolic disorders, undiagnosed diseases, Batten's disease, Tay Sachs, and diabetes. Participants may be grouped as active caregivers or bereaved caregivers who have lost their care recipient. Over one year, and possibly up to five years, participants will complete online surveys about their health, caregiving experiences, and social support networks. They will also take part in two-part phone interviews about their caregiving and social connections. Some may keep a diary every three months to record daily social activities, stress, and feelings. Blood samples may be collected annually for biological analysis. During the study, participants will provide information through surveys, interviews, and diaries, with some giving yearly blood samples. Researchers will assess changes in social, psychological, behavioral, and biological factors related to caregiving. The primary outcome is to track the natural history of caregiver stress over time. Participation involves various tasks and assessments done online or by phone, with follow-ups possible for up to five years to understand long-term effects.

This research aims to evaluate the software "Lipidica 1.0," designed to process lipidomic data from an in-house diagnostic device, for screening pancreatic cancer (PaC) in people at high risk due to family history, gene mutations, or hereditary pancreatic diseases. Pancreatic cancer often has a poor prognosis due to late detection and rapid progression. Early screening in high-risk groups may improve outcomes, and this study builds on previous findings showing distinct lipid profiles in pancreatic cancer patients. Participants are divided into two groups: those with confirmed resectable pancreatic cancer, who will have one baseline visit for blood sampling to analyze lipid profiles and tumor markers; and those at high risk without cancer, who will have two or three visits over up to 12 months. The high-risk group undergoes blood tests and medical imaging such as endoscopic ultrasonography, magnetic resonance, or computed tomography. The software's ability to distinguish between cancer patients and high-risk individuals without cancer is the main focus. Participants will attend visits for blood collection and imaging at the start and end of the study, with some having an additional visit based on initial results. Blood tests include lipidomic analysis, tumor markers CA 19-9 and CEA, HbA1c, and hCG for women of childbearing potential. Imaging assessments occur up to three times per participant. Researchers will analyze these data to verify the software's performance in differentiating disease presence. The study is expected to continue for about three years, with interim analysis after one year.

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 efficacy, safety, and tolerability of zeleciment rostudirsen (DYNE-251), given intravenously every 4 weeks, in ambulatory male children and adolescents aged 4 to 18 years with Duchenne muscular dystrophy (DMD) who have a specific mutation suitable for exon 51 skipping. This Phase 3 study aims to provide important information about this treatment option for this group of patients with DMD. The study includes three distinct periods: a Screening period lasting up to 6 weeks, a Placebo-Controlled Period of 72 weeks where participants are randomly assigned to receive either zeleciment rostudirsen or placebo every 4 weeks, and an open-label Long-Term Extension Period of up to 96 weeks during which all participants receive the study drug every 4 weeks. This design allows researchers to compare the treatment to placebo and then assess longer-term effects. Participants will be closely monitored throughout the study with regular assessments including the primary outcome of Rise From Floor (RFF) velocity measured at baseline and Week 73. Various secondary measures such as walking speed, stair climbing ability, lung function, patient global impressions, blood creatine kinase levels, and safety through adverse event monitoring and blood drug levels will be collected up to Week 169 or study completion. The total study duration including the extension is up to approximately 168 weeks. This thorough evaluation helps understand the treatment’s impact and safety over time.

This research aims to understand how patients undergoing in vitro fertilization (IVF) perceive and are motivated to receive additional genetic information about their embryos, specifically concerning risks for polygenic disorders. It focuses on patients who are already having their embryos tested for chromosomal abnormalities (aneuploidies) and explores their interest in learning about other inherited disease risks through genetic counseling. The study involves patients planning IVF with preimplantation genetic testing for aneuploidies (PGT-A) and evaluates their choices and responses to receiving polygenic risk information (PGT-P). Patients who meet the criteria will be offered participation by their IVF doctor before starting ovarian stimulation. After consenting and genetic counseling, they can choose to receive PGT-A results first and then decide about PGT-P results, or get a combined comprehensive report covering both. The PGT-P report may include risk predictions for diseases such as Type 1 and Type 2 Diabetes, heart conditions, several cancers, and other hereditary diseases. Each patient will also provide saliva samples for genetic ancestry testing to better understand the accuracy and applicability of polygenic risk predictions based on ethnic background. Participants will be followed for up to two years, during which their interest in polygenic testing will be measured. Genetic counseling will address the benefits and limits of each test, and the study will gather data on patient choices and motivations. Information from embryo biopsies and saliva samples will be collected and analyzed. The study is observational and does not affect the standard IVF treatment. Overall, the study seeks to inform future use of genetic testing in embryo selection and patient decision-making.