Niemann-Pick Disease

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 safety, tolerability, and effectiveness of N-acetyl-L-leucine (IB1001) compared to standard care for patients aged 4 years and older diagnosed with Niemann-Pick disease type C (NPC). This is a pivotal, randomized, double-blind, placebo-controlled, multi-center study designed to provide important information on this treatment's impact on NPC symptoms. The study includes a crossover design where participants receive both the study drug and placebo during separate periods. Participants will take N-acetyl-L-leucine or a placebo orally as granules suspended in water, orange juice, or almond milk. Patients aged 13 and older will receive a total daily dose of 4 grams divided into three doses, while those under 13 will receive weight-based dosing. The study consists of a baseline period followed by two treatment periods of about 12 weeks each, where participants switch from one treatment to the other. After completing the parent study, some patients may join an open-label extension phase providing up to three years of treatment. During the trial, participants will undergo assessments at several points, including before and after each treatment period. These include scales measuring ataxia severity, functional ability, disability, clinical global impressions from physicians, caregivers, and patients, and quality of life questionnaires. Researchers will monitor adherence and safety throughout the study. The trial continues until December 2030, with careful evaluation of the primary outcomes after each treatment phase and ongoing follow-up for those in the extension phase.

Researchers are conducting a multicenter, open-label observational study to assess the long-term safety and immune response to olipudase alfa therapy in young children with acid sphingomyelinase deficiency (ASMD), including Niemann-Pick diseases. This study focuses on pediatric patients under 2 years of age, aiming to gather real-world clinical data without altering their prescribed treatments. The study design is hybrid, allowing patients to participate without needing to travel to study sites. The study will observe patients receiving olipudase alfa as part of their routine clinical care. No treatments are administered by the study itself. The total study duration is 5 years, with an enrollment period up to 4 years and follow-up from 1 to 3 years for each participant. Data collected include safety events, immune responses to the drug, and laboratory and vital sign abnormalities over a 3-year period. Participants will provide informed consent through their parents or guardians and be monitored through clinical and laboratory assessments. Researchers will track adverse events, anti-drug antibody presence and levels, and any changes in laboratory tests and vital signs. The study collects data without influencing treatment decisions, aiming to understand long-term outcomes and safety during routine care.

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.

Niemann-Pick type C (NPC) disease is a rare and progressive neurodegenerative disorder that mainly affects the brain, liver, and spleen, but can also impact other parts of the body. Symptoms vary widely among individuals and may include seizures, difficulty moving or talking, or dementia. This research aims to better understand why NPC affects people differently by collecting detailed clinical and genetic information about the disease. Participants diagnosed with NPC will be involved in an observational study where their medical records will be reviewed to gather data on symptoms, duration, demographics, medications, and other test results. Each participant will have blood drawn once to analyze their DNA. This study will create the first and largest database combining clinical and genomic information to support future NPC research and potential therapeutic development. During the study, data on clinical findings and genomic markers will be collected and analyzed over a two-year period. Researchers will communicate with participants to discuss the study and address any questions. Participation may include providing medical records and a blood sample, with compensation of up to $190. The study focuses on understanding disease progression and variability rather than testing treatments.

Researchers are investigating Niemann-Pick Disease, Type C (NPC), a rare genetic disorder that causes progressive loss of nervous system function. This study aims to identify clinical and laboratory tests that may help determine if an investigational drug can slow the disease's progression. It also seeks to find clinical or biochemical markers to measure treatment response and to define the rate at which these markers change over time in NPC patients. Participants of any age with NPC undergo evaluations every six months during 4- to 5-day admissions. These include medical, neurological, and neuropsychometric exams; blood and urine tests; lumbar punctures to collect cerebrospinal fluid; eye exams and eye movement studies with special contact lenses; hearing tests; electroretinography to assess retina function; brain MRI scans; psychometric questionnaires; and pregnancy tests for females over 10 years old. Photographs may be taken for scientific use with consent. Throughout the study, researchers assess clinical and biochemical markers, including plasma oxysterols, to track disease progression. Participants may experience a range of neurological symptoms from mild to severe but must be stable enough to travel and undergo testing. Data collected will help guide future treatment trials and improve outcome measurements for NPC. Participation involves repeated visits and comprehensive testing over time to monitor the disease's course and response to potential treatments.

Researchers are studying patients with splenomegaly or those who have had a splenectomy without a known cause, focusing on the possible presence of Gaucher disease (GD) and Acid Sphingomyelinase Deficiency (ASMD). These conditions may be linked to monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM), which have been found more frequently among Gaucher and ASMD patients. The study aims to improve diagnosis of unknown causes of splenomegaly and undiagnosed cases of MGUS or MM in these patients. The study involves using standard diagnostic procedures for unknown splenomegaly and splenectomy patients, including collecting blood samples for a dry drop test (DBS). This test measures enzymatic and genetic activity related to Gaucher disease and ASMD, alongside analysis of LisoGl1 and LisoSM biomarkers. No specific treatment or intervention is applied since this is an observational study. Participants will undergo clinical evaluations and blood sampling to help identify the prevalence of Gaucher disease and ASMD over a 36-month period. Researchers will track how many patients with unknown splenomegaly or MGUS/MM have these enzyme deficiencies. The study is observational, with no treatment assigned, and participants will be monitored during their routine medical consultations throughout the study duration.

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.

This research aims to explore the relationship between plasma sphingolipid levels and the effectiveness of radiotherapy in patients with primary liver cancer, specifically hepatocellular carcinoma. The study focuses on key metabolites like ceramide, sphingosine, and sphingosine-1-phosphate, which play roles in cell signaling and apoptosis. Researchers hypothesize that these sphingolipid levels may predict how well radiotherapy works, helping to improve treatment strategies for liver cancer. The study is a single-center, prospective observational project involving 260 patients undergoing radiotherapy for liver cancer. Plasma samples will be collected before, during, and after treatment to analyze sphingolipid metabolites using advanced mass spectrometry techniques. Patients will be grouped based on their response to radiotherapy, classified by imaging criteria into responders and non-responders. The study also monitors radiation-induced side effects such as liver disease, enteritis, and bone marrow suppression. Participants will be followed for up to four years after radiotherapy, with assessments at multiple time points including 1, 2, 6, 12, 18, 24, 36, and 48 months. Clinical imaging, laboratory tests, and adverse event monitoring will be performed to correlate sphingolipid levels with treatment outcomes and safety. The main outcome measure is the disease control rate assessed 12 weeks post-treatment, with additional measures including progression-free survival, overall survival, and treatment tolerability.