Danon Disease

Researchers are studying the safety and effectiveness of RP-A501, a gene therapy using a modified virus to deliver the LAMP2B gene, in male patients 8 years and older with Danon Disease. This single-arm Phase 2 trial focuses on males who have a genetic variant of the LAMP2 gene and heart changes related to the disease. The goal is to understand how well this gene therapy works and how safe it is for this group of patients. Participants will receive one intravenous infusion of RP-A501, a gene therapy product made of a modified adeno-associated virus containing the human LAMP2B gene. This single dose is given during the treatment period, and patients are monitored over time to assess the therapys effects. The study does not include a comparison group and focuses solely on this treatment. During the study, participants will be evaluated at regular intervals up to 60 months after infusion. Assessments include measuring LAMP2 protein expression in heart tissue, heart size and function via left ventricular mass index, and biomarkers indicating heart injury such as high sensitivity Troponin I and NT-proBNP. The study also tracks event-free survival and safety outcomes. Patients must be able to comply with study procedures and attend follow-up visits throughout the trial.

Researchers are conducting an international observational study to understand the natural history of Danon disease, a rare genetic disorder that severely affects the heart. The study focuses on male patients aged 8 years and older, and female patients aged 8 to 50 years. It aims to describe the clinical progression, symptoms, key health events, and quality of life impacts under current standard care. This study collects both past retrospective and ongoing prospective data from patients to create a detailed and long-term view of Danon disease. Some participants will serve as an external control group for comparison in a separate gene therapy trial RP-A501. There are no interventions or treatments given as part of this study. Participants contribute clinical information through medical records and scheduled assessments including heart imaging echocardiograms, blood tests, walking tests, symptom questionnaires, and heart function classifications at enrollment and annually up to three years. Researchers will monitor heart muscle mass, biomarkers, functional status, and major health events like heart failure or transplantation. The study aims to provide comprehensive data over several years to improve understanding of Danon disease progression and management.

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 treatments impact and safety over time.

Researchers are conducting a multi-centre observational study focused on children with rare inherited cardiac conditions, particularly those diagnosed with cardiomyopathy before age 16. The study aims to better understand the genetic and environmental factors influencing these heart muscle diseases, including disease progression and response to treatments. By collecting genetic information and clinical data, the study seeks to identify new personalized treatment options for affected children. Participants include children with diagnosed inherited cardiac conditions and their parents. The study collects baseline demographic, imaging, and genotyping data primarily from routine clinical care, including whole genome sequencing. Some participants may provide blood or saliva samples for genetic and biomarker analysis. Family members of deceased patients might also donate stored tissue or samples if available. The study plans to follow participants over a 5-year period. During the study, researchers will access clinical data including health information and results from routine tests like echocardiograms. Some procedures may involve minimal risk, such as blood or saliva collection. The study focuses on monitoring the participants health outcomes and genetic markers to understand disease progression. The total follow-up duration for each participant is up to five years, with data collected throughout this period.

Researchers are evaluating a new family health communication tool called Lets Get REAL designed to increase youth involvement in real-time decisions about stem cell transplant and cellular therapy SCTCT. This pilot trial focuses on pediatric patients aged 8 to 17 years who are referred for SCTCT due to malignant or nonmalignant disorders. The study aims to assess the feasibility, acceptability, and appropriateness of this communication tool in helping families discuss treatment decisions. Participants, including youth in two age groups 8-12 and 13-17 years and their parents, will receive the Lets Get REAL tool to use up to one month before their SCTCT consultation visit. They will complete surveys before using the tool, up to one month after the consultation, and up to one month post-discharge from SCTCT. The consultation visits will be audio-recorded, and participants may opt to take part in a semi-structured interview within eight weeks after the consultation. During the study, participants will provide demographic and baseline information and complete several questionnaires measuring decision-making involvement, anxiety, communication, and satisfaction. Researchers will analyze both quantitative survey data and qualitative feedback to evaluate the tools impact. The total study participation spans from before the consultation through up to eight weeks after, with ongoing monitoring of youth-parent communication and decision-making processes.

Researchers are evaluating new advanced heart scan techniques using Cardiac Magnetic Resonance CMR imaging to improve diagnosis and risk assessment for people with rare heart muscle diseases, called rare cardiomyopathies. These diseases cause changes to the heart muscle that make it harder to pump blood, and are often hard to diagnose and manage. The study aims to better identify these conditions and predict future heart risks to enable more personalized care. The study uses novel CMR imaging biomarkers such as T1T2 Mapping for tissue characterization, Extracellular Volume Fraction to detect tissue changes, Feature Tracking Strain Analysis for subtle heart muscle function, and refined Late Gadolinium Enhancement patterns to more accurately show scarring or infiltration. These techniques go beyond standard heart scans and may help diagnose rare cardiomyopathies like cardiac amyloidosis, Fabry disease, Danon disease, and Noonan disease. Participants will undergo CMR scans using these advanced methods. Participants who join will have their heart imaged with these specialized CMR scans. The researchers will collect data on outcomes such as overall survival, cardiovascular death, heart transplantation, hospitalizations, and device implantations over 2 to 15 years. This will help track disease progression and evaluate the predictive value of the new imaging methods. The study is observational and aims to improve diagnosis, risk prediction, and management for people with rare cardiomyopathies.

Researchers are collecting important medical information to better understand several ultra-rare Glycogen Storage Diseases GSDs, including types 0a, 0b, VII, X, XII, XIII, XV, PRKAG2 syndrome, and Danon disease. The goal is to build a detailed natural history database that describes these rare diseases to help guide future treatment strategies. Participants include individuals diagnosed with these rare GSDs, and data will be gathered from multiple sources to capture the full clinical course of each condition. This observational study does not involve any treatment or intervention. Instead, it focuses on collecting data from medical records retrospectively and prospectively. The study is conducted at Duke University but includes participants receiving care elsewhere. Researchers will review medical charts over time to gather clinical, laboratory, biochemical, and imaging information relevant to the participants conditions. Participants will have their medical records continually reviewed throughout the study, which is expected to last an average of 10 years. Data collected will include demographics, diagnostic details, biopsy results, medical and family history, system reviews, and laboratory tests related to liver, muscle, nerve function, as well as urine and blood tests. The main outcome measured is the progression of the disease as confirmed by ongoing medical record review.

This research aims to collect CD34 hematopoietic stem cells HSC from peripheral blood andor bone marrow, along with mononuclear cells and granulocytes from peripheral blood. These cells will be used in laboratory studies and clinical treatments to develop new cell therapies for patients with inherited or acquired immune or blood disorders. The study includes adult patients with primary immune deficiencies or blood disorders and healthy adult volunteers to support the development and scale-up of gene therapies and cell engineering products. The main collection method for HSC is apheresis from peripheral blood after mobilization with daily subcutaneous injections of granulocyte colony stimulating factor G-CSF for 5 to 6 days, sometimes combined with Plerixafor. Some patients may also undergo bone marrow aspiration for clinical or research purposes. Mononuclear cells and granulocytes are collected from peripheral blood by apheresis, with or without pre-treatment using G-CSF alone or combined with dexamethasone, following standard care practices. Collected cells from patients may be used for clinical treatments under separate protocols or for laboratory research, while cells from healthy volunteers are used for research only. Participants provide blood andor bone marrow samples that may be stored or modified for research. Assessments include monitoring cell mobilization and collection through apheresis and bone marrow harvests. The collected cells contribute to laboratory studies of immune deficiencies, stem cell biology, and gene therapy development. The study evaluates the ability to mobilize and collect these cells safely and effectively. Participation involves collection visits and allows for ongoing research and potential clinical use of the samples in approved protocols.

Calciphylaxis, also called uremic calcifying arteriolopathy UCA, is a rare condition causing painful skin lesions due to small blood vessel calcification and clotting. This disease mainly affects patients with end-stage renal disease ESRD who require hemodialysis. Researchers are evaluating the safety and effectiveness of adding rheopheresis, a special blood filtration treatment, to the standard care for calciphylaxis in these patients through a prospective randomized controlled trial. In this study, participants will be randomly assigned to one of two groups. The experimental group will receive rheopheresis in addition to standard care, involving an induction phase of 3 sessions in the first week followed by 2 sessions weekly for 3 weeks, then a maintenance phase with 1 session per week up to week 11. The comparator group will receive sham-apheresis sessions on the same schedule, which mimics the procedure without actual filtration. Rheopheresis uses a machine to remove certain high molecular weight proteins from plasma to help treat microcirculation problems. Participants will be followed for 12 weeks during treatment with regular assessments of wound healing, pain levels, quality of life, antibiotic usage, hospital discharge days, survival, and inflammatory protein changes. The primary outcome is the percentage of patients achieving complete healing of calciphylaxis lesions after 12 weeks. Secondary outcomes include partial healing, new lesion occurrence, pain and analgesic use, and overall survival at 12 weeks and one year. Safety and efficacy data will help determine the added value of rheopheresis in calciphylaxis care.