X-Linked Adrenoleukodystrophy

Researchers are evaluating the efficacy and safety of Leriglitazone in adult male subjects with cerebral adrenoleukodystrophy (cALD), a progressive neurological condition. This phase 3 clinical trial aims to compare Leriglitazone treatment with a placebo to better understand its impact on disease progression and patient outcomes. Participants included are adult males with confirmed progressive cALD who are not recommended or willing to undergo hematopoietic stem cell transplantation (HSCT). Participants will be randomly assigned to receive either Leriglitazone at a dose of 15 mg/ml once daily, starting at 10 ml volume, or a placebo matching the study drug in appearance and taste. The study uses a triple masking design to ensure unbiased results. The treatment period spans up to 36 months, with interim analyses at 18 and 27 months to assess outcomes. Throughout the study, participants will be monitored for the primary outcome of time to death or becoming bedridden with permanent ventilatory support, whichever occurs first. Secondary outcomes include changes in the Loes score, which measures brain lesion severity. Safety and functional status will also be assessed, alongside monitoring for cognitive ability and overall neurological function. The trial is expected to conclude in May 2027.

This research aims to evaluate the long-term safety outcomes of patients with Cerebral Adrenoleukodystrophy (CALD) who have been treated with elivaldogene autotemcel (eli-cel, tradename Skysona) in a real-world, post-marketing setting. The study particularly focuses on tracking newly diagnosed malignancies and assessing major functional disability-free survival over time in participants with more advanced early active CALD. This observational study includes a specific subpopulation required by the US FDA as part of accelerated approval conditions. Participants in this registry study will be followed for up to 15 years after receiving eli-cel treatment. No new investigational drug will be given during the study. The study plans to enroll 120 participants treated with eli-cel, including a subgroup of 24 participants with more advanced early active CALD, tracked separately for effectiveness outcomes. Data will be collected longitudinally to assess the safety and effectiveness of eli-cel over this extended period. During the study, participants will receive follow-up care by US-based physicians who can submit required data. Researchers will monitor adverse events including malignancies and insertional oncogenesis, as well as survival without major functional disability. Other evaluations include overall survival, serious adverse events, and detailed genetic analyses in the subpopulation with newly diagnosed hematologic malignancies. This long-term observational approach allows comprehensive safety and outcome data collection over 15 years post-infusion.

Researchers are conducting a prospective, observational registry study on Adrenoleukodystrophy (ALD), including patients with confirmed or presumed ALD mutations. The study aims to understand the natural history, disease progression, and outcomes in affected individuals, including children, adolescents, adults, and women with ALD. The research also seeks to develop biomarkers from collected biospecimens to potentially predict disease progression and support future interventions. Participants provide medical histories and allow collection of various biospecimens such as buccal swabs, blood, stool, and urine samples, which are stored in a biorepository. The study collects clinical and epidemiological data through medical record reviews and self-reported questionnaires every six months. Eligible participants include those diagnosed by newborn screening, family history, or other means and those with confirmed or presumed mutations. During the study, participants may be asked to provide longitudinal samples and medical information over a period of up to 10 years. Researchers monitor clinical data to better understand disease progression and gather valuable biological data. The registry and biorepository serve as resources for ongoing and future ALD research, supporting efforts to identify prognostic markers and improve patient care.

Researchers at the University of Texas Health Science Center at San Antonio are studying individuals with chromosome 18 abnormalities to better understand the genetic causes and effects of these conditions. The study aims to identify how growth hormone deficiency and other genetic factors impact brain structure and cognitive function, as well as physical and behavioral traits. The goal is to provide comprehensive medical and educational resources, perform clinical and basic research, and develop treatments to improve the lives of affected individuals. Participants undergo various evaluations including genetic testing of DNA from subjects and their parents to determine genotype. Clinical assessments include testing growth hormone and other hormone levels, psychiatric and neuropsychological evaluations, audiology and ENT exams, brain MRI scans, genetic dysmorphology, neurology, dental, speech pathology, gastrointestinal, orthopedic, and ophthalmologic examinations. These assessments are longitudinal, with participants of a wide age range, and not all tests apply to every participant at every visit. Participants will be involved in thorough clinical evaluations and multiple specialized exams over time to gather detailed health data. These include hormone tests, brain imaging, behavioral and cognitive assessments, and physical exams. Researchers will monitor growth hormone status and other health markers to understand the condition's impact. The study is ongoing and designed to provide long-term data to guide future treatments and support. Total participation time varies depending on individual assessments and follow-up needs.

Researchers are evaluating a non-invasive prenatal diagnosis (NIPD) method for single-gene disorders (SGD) using cell-free fetal DNA (cffDNA) found in maternal blood. This approach offers early and accurate diagnosis from 9 weeks of pregnancy without the miscarriage risks linked to invasive procedures. The study aims to broaden the use of this method to any monogenic disorder by leveraging a collaborative French network, improving current diagnosis options which are limited and mostly research-based. The study involves taking blood samples from pregnant women who are undergoing invasive prenatal diagnosis or counselling due to family history of specific single-gene disorders. These disorders involve mutations in genes such as HBB, CFTR, FMR1, SMN1, and others. Blood plasma is collected and stored for analysis to detect fetal genetic mutations using advanced sequencing techniques. The method is targeted, focusing on specific DNA regions related to the family’s disorder, avoiding broader genome sequencing. Participants will provide blood samples during routine prenatal diagnosis visits, and their samples will be analyzed for the presence and concentration of fetal DNA. Researchers will measure how accurately they can classify affected or unaffected fetuses and monitor inconclusive results. Secondary measures include DNA concentration, sequencing quality, and turnaround time for results. The study will follow participants until birth in some cases, comparing prenatal findings with newborn genotypes. Participation duration varies depending on prenatal visits and follow-up care.

This research investigates disease progression in women diagnosed with X-linked adrenoleukodystrophy (ALD) through an observational, minimally interventional study conducted in France. Participants will be followed for at least two years or until they begin treatment for ALD or withdraw, with possible extension beyond two years based on interim findings. The study aims to gather detailed information on disease changes over time without altering prescribed clinical care. Participants will undergo yearly assessments, including MRI scans of the brain and spinal cord, and evaluations of body sway, disability status (EDSS), daily living activities (ADL), pain levels (VAS), and quality of life (SF-36 questionnaire). Blood samples will be collected to measure plasma biomarkers, and participants will maintain a monthly falls diary. These assessments will occur at baseline and annually, continuing with yearly visits if the study extends beyond two years. During the study, participants will complete questionnaires and undergo imaging and physical assessments at scheduled visits. Researchers will monitor changes in spinal cord magnetization transfer ratio, spinal cord and brain imaging parameters, body sway, disability, pain, falls frequency, quality of life, and specific plasma biomarkers over time. The study does not involve any specific drug or intervention and will not interfere with treatments prescribed by the participants' healthcare providers.

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 treatment’s impact and safety over time.

Researchers are studying adults with rare and complex genetic syndromes that affect multiple body systems and often include intellectual disability. These patients typically receive specialized care from multiple specialists during childhood, but as medical advances have extended life expectancy, many are now living into adulthood. The study aims to understand the medical needs, comorbidities, medication use, and quality of life impacts for adults with these rare syndromes, addressing a gap in adult care and guidelines. This research involves a retrospective review of medical files, including medical history, laboratory results, additional tests, and records of physical and psychological complaints. There is no active treatment or intervention, as the study collects and analyzes existing data to gain insights about health issues and medication adaptations needed for these syndromes. Participants' medical records will be analyzed to evaluate the presence of physical health problems, laboratory values, physical and psychological complaints, and medication use over a one-year period. The study uses statistical software for analysis and aims to improve understanding of adult care needs for these rare genetic conditions. The study began in October 2018 and will continue through January 2030.

Researchers are evaluating targeted therapeutic exercises for individuals with neurodegenerative diseases that affect walking. The study aims to improve how clinicians assess disease severity, apply exercise interventions that match the disease pathology, and measure the impact on balance and walking. The research focuses on conditions such as leukodystrophy, ataxia, LBSL, and adrenomyeloneuropathy among others. Participants will engage in an individually designed home exercise program focused on addressing walking impairments. This program will be remotely supervised to test the feasibility of such interventions and to optimize outcome measures that can be used in clinical monitoring and future trials. The exercise intervention will be tailored to each participant's condition and delivered in a home setting. During the study, participants will be assessed on changes in motor function and sleep quality using tools like the NeuroQOL lower extremity measure over a 12-week period. Researchers will monitor balance and walking improvements as well as the feasibility of remote supervision. The study includes healthy volunteers who can stand and walk for specific durations and involves ongoing clinical evaluations to ensure safety and measure progress. Total participation duration and follow-ups are designed to support these goals.

Researchers are evaluating a gene therapy approach to treat X-linked adrenoleukodystrophy (X-ALD), a serious neurological disorder caused by mutations in the ABCD1 gene. This trial focuses on using a self-inactivating lentiviral vector called TYF-ABCD1 to deliver a functional ABCD1 gene. The aim is to assess the safety and effectiveness of this therapy when given through both intrathecal (into the spine) and intravenous (into the vein) injections, potentially offering treatment options beyond the early stages of the disease. The treatment involves direct delivery of the TYF-ABCD1 lentiviral vector carrying the working gene into the central nervous system and bloodstream via intrathecal and intravenous routes. This method targets patients with symptoms at various stages and seeks to simplify the treatment process compared to traditional stem cell transplantation, reducing associated risks. Participants will receive the gene therapy through these injections as part of the protocol. During the study, participants will be monitored closely through scheduled assessments including vital signs, physical exams, and imaging to evaluate safety and measure disease progression. The main outcomes include tracking any treatment-related adverse events and assessing changes in disease status over time, with follow-up lasting from one day up to three years. The study provides ongoing evaluation of the therapy's impact on the disease course and participants' neurological function.