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 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 building a comprehensive registry for Hepato-Renal Fibrocystic Diseases (HRFD), which include rare conditions like Autosomal Recessive Polycystic Kidney Disease (ARPKD) and related disorders such as Joubert syndrome and congenital hepatic fibrosis. The goal is to gather clinical and genetic information and create educational resources to help families, doctors, and genetic counselors better understand these diseases. This observational study is designed to support research progress and community awareness through a shared database and biospecimen resources. Participants may choose to contribute to various parts of the study, including a clinical database, genetic testing, tissue donation, and educational resources. Medical records will be reviewed, with data entered into a secure database after removing personal identifiers. Blood or saliva samples may be collected from patients and their parents for genetic analysis, with samples stored at a specialized biorepository. Tissue samples from procedures like nephrectomy or autopsy may also be collected and stored for research. Participants will provide access to their medical information without needing to visit the study center. Data collection includes past, current, and future medical records, with annual updates for ongoing participation. Genetic and tissue samples will be stored and used to support research. The study team monitors the development of this resource over five years to enhance knowledge and treatment options for HRFD. Participation duration varies depending on continued involvement and consent.

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 and/or their guardians must agree to participate, with the study lasting until October 2026.

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 I/II study also includes a long-term extension phase to gather additional data. The study includes two groups: one receiving DFT383 and another continuing standard care without the gene therapy to provide comparative data in this rare disease. Participants in the treatment group (Cohort 1) will receive DFT383 in a staggered dosing approach across three subgroups and will be involved 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 continue their standard treatment with cysteamine and participate only in the Core Phase, which lasts up to 24 months. Both cohorts will run in parallel at investigational sites. During the study, participants will undergo various assessments including measurements of kidney function, reversal of renal Fanconi syndrome, blood tests, and eye examinations for corneal cystine crystals. Researchers will monitor adverse events, quality of life, and other health indicators over time. The study aims to track these outcomes over the Core and Extension Phases, with long-term safety and efficacy being closely observed throughout the total duration of participation.

Researchers are evaluating a phase 1b/2a 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 that affects many organs. Symptoms typically begin around 6 months of age, and without treatment, kidney failure usually occurs between 6 and 12 years. Advances like kidney transplantation and cysteamine therapy have improved survival, allowing patients to live into adolescence and adulthood, but they face complex health issues requiring ongoing care. The study aims to expand an existing European database into a cohort study to collect comprehensive clinical and quality of life data from more countries, enhancing patient monitoring and care standards. This observational cohort study will gather detailed clinical information, personal data including quality of life, and genetic information at inclusion. Patients will have the opportunity to contribute their own quality of life data and receive feedback on general results. The study does not involve experimental treatments but focuses on data collection to better understand patient outcomes and care effectiveness across Europe. Participants will be followed over time with assessments including kidney function tests, recording the need for renal replacement therapy, and monitoring neurological, endocrine, and treatment compliance outcomes. Data will be collected through patient files, physician visits, and questionnaires at yearly intervals up to three years and throughout study completion. This long-term follow-up aims to identify care improvements and support high standards of management for cystinosis patients.

Researchers are evaluating a genetic newborn screening program for two rare inherited diseases, cystinosis and primary hyperoxaluria (PH), in Germany. These diseases are not detected by routine newborn screening methods but have known common genetic mutations. The study aims to determine if including cystinosis and PH in the general newborn screening should be recommended by comparing early diagnosed infants to those diagnosed later by symptoms, assessing whether early diagnosis and treatment improve outcomes. The study tests newborns using the same dried blood spot card collected for routine newborn screening to detect specific common mutations in the genes associated with cystinosis and PH. If two mutations are found for cystinosis, parents are immediately informed and further diagnostics are arranged. For PH, if one mutation is detected, parents are asked to provide urine samples for additional testing. The study plans to screen 200,000 newborns by 2025, with possible program expansion based on results. Parents who consent allow molecular genetic testing and data sharing for follow-up. Confirmatory tests and clinical care referrals are organized for newborns with positive screening results. Researchers will track the number of newborns diagnosed with cystinosis and PH and those carrying heterozygous mutations. The study includes monitoring for up to 12 months and evaluates whether early detection leads to better health outcomes compared to traditional diagnosis methods.

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 evaluating the safety, pharmacokinetics, and pharmacodynamics of NPI-001 oral solution in patients with cystinosis who are aged 10 years and older. This study compares the ability of NPI-001 to reduce cystine levels with the current treatment using cysteamine. The research aims to understand how these treatments behave in the body and their effects on cystine reduction in this patient group. Participants will receive a single dose of either the current cysteamine treatment in tablet form at their usual dose or a single dose of NPI-001 (N-acetylcysteine amide) oral solution at a molar equivalent dose. The study design is non-randomized and open-label, meaning participants and researchers know which treatment is given. This phase 1/2 study focuses on comparing these two treatments directly. During the study, participants will be monitored for cystine levels over one day to assess treatment effects. They must be able to stop cysteamine therapy for two days before dosing. Safety and pharmacokinetic data will be collected, including blood samples. Participants need to stay at a clinical phase 1 unit or similar setting for up to 3 days for assessments and monitoring. The study is sponsored by Nacuity Pharmaceuticals, Inc. and is expected to continue until August 2026.