Pompe Disease

This research is a global, multicenter, prospective observational registry studying patients with Pompe disease, including both late-onset (LOPD) and infantile-onset (IOPD) forms. It enrolls both untreated patients and those receiving approved therapies to better understand the long-term safety, real-world effectiveness, and quality of life impacts of treatments for Pompe disease. The study also aims to describe the natural history of untreated Pompe disease. Participants include groups receiving different enzyme replacement therapies such as Cipaglucosidase alfa with Miglustat, other approved ERTs like Alglucosidase alfa or Avalglucosidase alfa, as well as untreated individuals who are not on any medical therapy for Pompe disease. No experimental treatments are given as this is an observational study tracking real-world treatment use and outcomes. During the study, participant data on adverse events, treatment effectiveness, quality of life, and patient-reported outcomes will be collected over a period of at least five years. Researchers will monitor safety through the frequency of adverse events and serious adverse events. Participants' health and treatment impacts will be regularly evaluated to provide long-term insights into Pompe disease management and outcomes.

This observational study follows patients diagnosed with Pompe disease who are receiving or preparing to receive enzyme replacement therapy. The research aims to monitor long-term outcomes and the overall health of these patients over an extended period, providing valuable information about the disease progression and treatment experience. Participants will be observed prospectively without any investigational treatments assigned by the study. All enrolled individuals are those already receiving enzyme replacement therapy or preparing to begin it, and the study collects data on their health and treatment outcomes over time. During the study, patients will be regularly monitored for all-cause morbidities over a 10-year period. Researchers will collect health information to understand the long-term effects of enzyme replacement therapy in Pompe disease. Participation involves ongoing health assessments, and the study extends until December 2026, providing extensive long-term outcome data.

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 studying the safety and effectiveness of a single dose of nexiguran ziclumeran (NTLA-2001) compared to a placebo in people with hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN). This phase 3, multinational, randomized, double-blind, placebo-controlled trial involves about 60 participants with this nerve disease and genetic condition affecting the peripheral nervous system. Participants will be randomly assigned to receive a single intravenous infusion of either nexiguran ziclumeran 55 mg or a placebo of normal saline. To give everyone a chance to receive the study drug, participants may switch to the other treatment group at either 12 or 18 months, depending on specific study criteria. The study is designed to compare the effects of the drug and placebo over time. During the study, participants will be monitored for nerve function using the Modified Neuropathy Impairment Score +7 (mNIS+7) over 18 months and blood levels of serum transthyretin at 29 days and 18 months. Quality of life, body mass index, and other health measures will also be evaluated. The study includes careful safety monitoring and will last up to 18 months with ongoing assessments to track participants' nerve health and overall well-being.

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 conducting a multicenter, prospective observational study to understand the natural history of Charcot-Marie-Tooth Disease, Type 4J (CMT4J), a rare neurodegenerative and neuromuscular condition confirmed by specific genetic testing. The study will enroll 20 participants of any age who have a molecularly confirmed diagnosis of CMT4J. The purpose is to collect detailed health information and disease progression data over time, without providing any investigational treatments. Participants will follow a uniform protocol with visits scheduled every 12 months plus a 4-week window, for up to 2 years. At each visit, researchers will collect demographic and medical history data, perform physical and neurological exams, standard lab tests, and use several disease outcome measures. Additional assessments may include neuropsychological tests, nerve conduction studies, muscle MRI, pulmonary function tests, and scoliosis x-rays. Early termination visits are planned if participants leave before completing the study. Throughout the study, participants will undergo thorough evaluations to monitor their condition and collect data relevant to CMT4J progression. This includes clinical exams, imaging, lab tests, and questionnaires. Researchers will use this information to study disease patterns and outcomes over the 2-year follow-up period. No investigational products are administered, and visits may be unscheduled if necessary with approval. Participants are expected to comply with study procedures and travel requirements.

Researchers are studying DNL952 in adults with late-onset Pompe disease (LOPD) to understand its safety, how the body processes it, and its effects. This Phase 1, open-label, multicenter trial focuses on evaluating safety and tolerability across different dose levels of DNL952 in participants with LOPD. The study is sponsored by Denali Therapeutics Inc. and aims to gather important information about treatment impact on this condition. The study involves giving DNL952 through repeated intravenous doses to adult participants diagnosed with LOPD. Participants are grouped into several cohorts, some of which require prior enzyme-replacement therapy with specific drugs, while others have not received such therapy recently. The study is non-randomized and open-label, meaning all participants receive the investigational drug and know the treatment they receive. Participants will be monitored for 48 weeks to assess treatment-emergent adverse events, infusion-related reactions, and pharmacokinetic parameters such as drug concentration over time. Safety and tolerability data will be collected alongside laboratory and clinical assessments. This involves tracking how the drug behaves in the body and its potential side effects. The study lasts about a year, including screening and treatment periods, with careful follow-up to understand the drug's effects in people with LOPD.

This research is focused on patients with slowly progressive neuromuscular diseases who experience breathing difficulties requiring support from non-invasive ventilation (NIV). The study aims to assess the safety and effectiveness of a new type of NIV called volume-targeted ventilation (VT-NIV), which adjusts the pressure delivered to the lungs to reach a specific breath volume. This approach is being evaluated to better control carbon dioxide levels, which are linked to clinical outcomes in these patients. Participants currently using fixed bi-level NIV will undergo a two-night hospital stay for assessment. On the first night, their carbon dioxide control will be measured using their usual ventilator. On the second night, they will switch to VT-NIV. After discharge, participants will use VT-NIV at home for three months. The study will observe both patients with well-controlled and poorly controlled carbon dioxide to evaluate safety and potential benefits of VT-NIV. During the study, researchers will collect data from the ventilation devices and patient questionnaires to assess adherence and quality of life. Measurements include overnight transcutaneous carbon dioxide levels, oxygen desaturation, sleep comfort, and health-related quality of life. The follow-up visit at three months will review these outcomes and monitor participant safety. The total participation includes the initial two-night hospital stay and the three-month home use period.

Researchers are collecting safety data worldwide on women and their babies who have been exposed to avalglucosidase alfa during pregnancy and breastfeeding. The study aims to understand the potential risks of avalglucosidase alfa on pregnancy outcomes, maternal health issues, and any adverse effects on the developing fetus, newborn, and infant. This observational study looks at both past and current exposures to gather comprehensive safety information. The study focuses on pregnant women diagnosed with Pompe disease who have received avalglucosidase alfa either during pregnancy or lactation, as well as infants born to parents with Pompe disease who were exposed to the drug. Avalglucosidase alfa is given through intravenous infusion, and exposure is tracked through reports submitted to the study sponsor and patient registries. There are no comparison groups since this is an observational safety study. Participants will be followed for about 10 years to collect data on maternal complications, pregnancy outcomes, and infant health. Infant growth and development will be closely monitored for at least the first year of life. The study relies on safety reports and registry data to assess the long-term effects of avalglucosidase alfa exposure during pregnancy and breastfeeding.

This research aims to determine if physiotherapists can use waveform traces from a cough assist machine to identify abnormal airway responses during treatment. It focuses on patients with neuromuscular diseases and studies how different settings of the cough assist device, especially breath and cough pressures, affect patient responses. The goal is to provide clinical guidance to physiotherapists for assessing and managing these airway responses. During the study, participants will undergo breathing tests including spirometry, peak cough flow, and sniff nasal inspiratory pressure to assess baseline lung function and exclude those with breathing conditions. A nasal camera will be used to observe the voice box while the cough assist device is applied via a face mask. The device's waveforms will be recorded and analyzed alongside video recordings to see if voice box responses can be identified from these patterns. The cough assist treatment is delivered by an experienced physiotherapist following established protocols. Participants will be monitored for about 30 minutes each during the study. The main assessments include waveform analysis from the cough assist device and nasal endoscopy video recordings of the voice box. These observations will help researchers better understand patient responses to cough assist therapy. The study involves no additional long-term follow-up but requires participants to complete the breathing tests and allow video and device recordings during the session.