Cystinosis

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 studying hepato-renal fibrocystic diseases HRFD, which include rare conditions like Autosomal Recessive Polycystic Kidney Disease ARPKD, Joubert syndrome, Bardet Biedl syndrome, Meckel-Gruber syndrome, congenital hepatic fibrosis, Caroli syndrome, oro-facial-digital syndrome, nephronophthisis, and glomerulocystic kidney disease. The study aims to create a coordinated clinical and genetic database to improve diagnosis, treatment, and research progress by sharing information and biological samples among institutions. Participants can contribute to a clinical database by allowing access to their medical records, which will be anonymized and entered into a shared database. Optional parts of the study include genetic testing through blood or saliva samples from the participant and their parents, as well as donating tissue samples collected during medical procedures or autopsies. These samples will be stored in specialized repositories to support future research. Participants will have their medical records reviewed periodically, with initial data entry and annual follow-ups for the duration of the study or until they choose to withdraw. Genetic and tissue samples will be processed and stored securely. The main outcome is the development and maintenance of a comprehensive translational resource for HRFD over five years. The study does not require clinic visits and involves minimal participant burden while contributing valuable data and materials for ongoing research.

Nephropathic Cystinosis NC is a rare inherited disease caused by a deficiency in the cystine lysosomal transport protein, cystinosin. This condition leads to a generalized lysosomal storage disorder and is usually treated with cysteamine. Bone problems have been identified as a late complication in NC patients, especially during adolescence or early adulthood, possibly due to cysteamine toxicity or effects from the CTNS mutation. The study aims to better understand how cysteamine affects bone cells and to describe the bone health of NC patients according to their genetic background. This observational study involves NC patients who are currently receiving cysteamine treatment. Researchers will collect blood samples to evaluate the effect of cysteamine on the formation and activity of bone-resorbing cells called osteoclasts. The study will assess this relationship based on patients genotypes to understand differences in bone disease progression. Participants will provide a 25 mL blood sample for analysis of osteoclastic cells. Researchers will measure the number of specific cells called Tartrate-resistant acid phosphatase TRAP positive cells one day after sample collection. The study also includes clinical assessments of patients bone status depending on their genotype. Participants andor their guardians must agree to participate, with the study lasting until October 2026.

Cystinosis is a rare inherited disease caused by mutations in the CTNS gene, leading to the buildup of cystine in cells and causing severe damage, especially to the kidneys, with symptoms starting early in life. This condition also affects other organs, including bones, where premature aging and musculoskeletal problems may develop. Researchers aim to better understand how mitochondrial energy metabolism dysfunction might contribute to these complications in cystinosis patients. The study involves patients with genetically confirmed nephropathic cystinosis who are receiving oral cysteamine and are undergoing conservative treatment on their native kidneys. Researchers will analyze mitochondrial function by measuring membrane potential and respiratory chain activity in circulating monocyte cells. Clinical and biological assessments including metabolomic analysis of blood and urine samples will be performed to characterize musculoskeletal disorders. Participants will be monitored over 24 months with various evaluations including blood pressure, bone deformities, muscle strength tests, and laboratory tests such as inflammatory markers and vitamin levels. Researchers will track mitochondrial membrane potential and oxygen consumption rates in cells, along with other metabolic markers. The study seeks to identify underlying mechanisms of bone disease and premature aging in cystinosis to guide future therapies.

Cystinosis is a rare inherited metabolic disorder causing cystine to build up in many organs, initially affecting kidney function in children and potentially leading to kidney failure by early school age if untreated. As patients live longer due to treatments, other organs like eyes, muscles, endocrine organs, and the central nervous system may also be affected. This study aims to develop a patient-reported outcome measure PROM to assess the quality of life specifically for children, adolescents, and young adults with cystinosis in several languages including German, English, Spanish, and French. The development of this PROM will occur in three phases with participants from Germany, the United States, Spain, and France. It starts with focus interviews involving young patients aged 8 to 26 and their parents, followed by pilot testing and cognitive debriefing of the initial instrument. Finally, a field test and retest will be conducted to refine the questionnaire. Different age groups will have tailored versions, and the instrument will include parent-reporting for children aged 0 to 26. Participants will complete interviews and questionnaires assessing various aspects of their quality of life. The study includes repeated testing to check reliability, with questionnaires completed again after two weeks by a subset of participants. Researchers will also use established generic quality of life tools alongside the new cystinosis-specific PROM. The study runs from 2022 to mid-2025 and aims to produce a validated, easy-to-use tool for research and patient care.

Researchers are evaluating the safety, tolerability, and effectiveness of DFT383, a cellular gene therapy, in children aged 2 to 5 years with nephropathic cystinosis. This open-label, multi-center, phase III study includes a Core Phase and a long-term Extension Phase to gather detailed data on this rare disease. The study features two groups one receiving DFT383 and another continuing with standard care for comparison. Participants in the DFT383 group Cohort 1 will receive the gene therapy in a staggered dosing approach across three sub-cohorts. This group will participate in both the Core Phase lasting up to 32 months and a long-term Extension Phase lasting up to 13 years. The comparison group Cohort 0 will not receive the gene therapy but will continue their usual cysteamine treatment during the Core Phase, which lasts up to 24 months. Throughout the study, participants will undergo regular monitoring including safety assessments, kidney function tests, and evaluations of renal Fanconi syndrome reversal. Researchers will also track quality of life and long-term health outcomes such as kidney failure and malignancy. The study includes frequent laboratory tests, vital signs checks, and corneal crystal assessments, with extended follow-up to understand long-term effects of DFT383 and standard care treatments.

Researchers are evaluating a phase 1b2a trial studying sequential alpha-beta depleted hematopoietic stem cell transplantation HSCT and kidney transplantation KT in patients who need a kidney transplant. The goal is to prevent kidney rejection after transplant without lifelong immunosuppression, reducing the risk of chronic rejection and the need for repeated transplants. This trial is for patients with conditions such as SIOD, FSGS, cystinosis, SLE nephritis, or chronic kidney disease stage 4, among others. Participants will undergo one of two conditioning regimens prior to receiving alpha-beta depleted HSCT from a donor. At least three months after HSCT, if donor myeloid engraftment is confirmed and there are no signs of kidney rejection, patients will receive a living donor kidney transplant from the same donor. Pharmacological immunosuppression used for the kidney transplant will be tapered off by day 90 after the transplant if no rejection occurs. The study begins with a safety evaluation in a small group of patients and may expand based on safety and feasibility. During the study, patients will be closely monitored for donor cell engraftment, kidney function, and any signs of graft-versus-host disease GvHD. Researchers will measure how many patients can stop immunosuppression by 90 days after kidney transplant, kidney function at one year, donor chimerism, and any acute or chronic GvHD. Follow-up will include assessments up to five years post-transplant to observe long-term outcomes such as secondary malignancies. Total participation length may extend up to a decade based on study timelines.

Cystinosis is a rare lysosomal storage disease caused by mutations in the CTNS gene, leading to cystine buildup in cells and resulting in multi-organ dysfunction. Symptoms typically begin around six months of age, and without treatment, kidney failure occurs between 6 and 12 years. Advances including kidney transplantation and cysteamine therapy have improved outcomes, allowing patients to live into adolescence and adulthood, although they face complex health challenges requiring ongoing care. This research is an observational cohort study that builds on a previous European registry. It aims to collect extensive clinical and personal data, including quality of life information, from a larger number of European countries. Patients can actively participate by entering their own quality of life data and receive feedback on overall study results. This project is an academic effort not driven by pharmaceutical companies. Participants will be followed over time with data collected on kidney replacement therapy use, kidney function eGFR, and various secondary health outcomes such as endocrine issues, cognitive function, neurological symptoms, treatment compliance, and genetics. Data will be collected at inclusion and annually for up to three years. The study will help evaluate patient outcomes and guide improvements in care standards.

Researchers are collecting information from patients with rare kidney diseases to support research and improve care. This National Registry of Rare Kidney Diseases RaDaR aims to develop clinical guidelines, audit treatments and outcomes, and help develop future therapies by gathering comprehensive data. Rare kidney diseases often have genetic causes and affect patients from childhood into adulthood, but their rarity makes research and treatment development challenging. The registry gathers clinical data and biological samples from various rare kidney disease groups, each focusing on conditions like Alport Syndrome, APRT Deficiency, Polycystic Kidney Disease, and many others. It connects patients and clinicians and allows patients to contribute information about their quality of life. This infrastructure enables identification of patient groups for clinical trials, biomarker development, and genotype-phenotype studies. Participants provide clinical and disease-specific information over time, which supports epidemiological and translational research. The registry facilitates patient recruitment for studies, improves patient and clinician education, and provides access to current knowledge about rare kidney diseases. The registry is ongoing and primarily includes UK patients but also accepts international participants consented through UK NHS hospitals.

Researchers are conducting a patient registry and natural history study called Coordination of Rare Diseases at Sanford CoRDS to support research on rare diseases. CoRDS is an international registry that connects patients with rare, undiagnosed, or uncommon diseases to researchers studying over 7,000 rare diseases. This program aims to help advance treatments and cures by facilitating easy collaboration between patients, advocacy groups, and researchers. It is based at Sanford Research in Sioux Falls, South Dakota, and is free for patients to join and for researchers to access. Participants provide contact, sociodemographic, and health information, which is entered into CoRDS and linked to a unique coded identifier. Examples of collected data include name, mailing address, phone number, email, date and place of birth, sex, gender, ethnicity, family history, and diagnosis-related information. De-identified information may be shared with approved researchers after review by an Institutional Review Board and expert panel. Some data may also be shared with other databases and patient advocacy groups, with protections to prevent misuse for research purposes. Participants are contacted yearly to confirm continued participation and to update their information. If a parent or legal guardian consents for a minor, the participant will be contacted at age 18 to provide their own consent. The primary goal is to accelerate research by connecting individuals interested in rare disease research with scientists over a long period of up to 100 years. There is no treatment given, as this is an observational registry study.