Adrenoleukodystrophy (ALD)

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.

Cognitive problems often occur in people with neurodegenerative diseases. Researchers are exploring how sleep disorders relate to the progression of these diseases by studying their clinical signs, brain imaging, and biological markers. This observational study aims to better understand the mechanisms behind sleep problems in neurodegenerative conditions. Participants will have assessments including neuropsychological tests, brain MRI scans, and electroencephalograms. Biological samples will also be collected to measure markers like plasma Ab2-42 levels. These evaluations will help observe changes in sleep quality, cognitive function, heart rate variability, and other relevant outcomes over time. People in the study will undergo baseline and follow-up tests such as the Pittsburgh Sleep Quality Index (PSQI), Montreal Cognitive Assessment (MoCA), and Addenbrooke's Cognitive Examination (ACE-III). Researchers will monitor sleep patterns and biological markers to track disease progression. The study includes adults aged 30 to 80 years and will continue through June 2030, providing long-term data on sleep disorders linked to neurodegeneration.

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 are collecting clinical data from patients with various non-malignant disorders undergoing hematopoietic stem cell transplantation (HSCT) using a reduced-intensity chemotherapy-based regimen. This regimen includes alemtuzumab and other drugs and aims to reduce graft failure and help immune system recovery. The study follows patients with conditions like primary immunodeficiency, inherited metabolic disorders, hereditary anemias, and inflammatory diseases to better understand treatment outcomes. Participants will receive one of three types of stem cell transplants: umbilical cord blood, bone marrow, or peripheral blood stem cells. All receive a reduced-intensity conditioning regimen that involves alemtuzumab, melphalan, thiotepa, fludarabine, and hydroxyurea, administered according to the treating physician's guidance at the UPMC Children's Hospital of Pittsburgh. This observational study gathers medical data without altering standard care. During the study, researchers will monitor outcomes such as the occurrence of acute graft versus host disease (GVHD) and overall survival for up to five years after transplantation. They will also assess engraftment levels, the timing of immune system recovery, the use of immunosuppressant medications, and donor leukocyte infusions. Medical information will be collected from patients' charts after informed consent, with follow-up extending up to five years to evaluate long-term results.

Researchers are evaluating the use of dimethyl fumarate to treat motor problems in adults with Adrenomyeloneuropathy (AMN), a form of X-linked Adrenoleukodystrophy caused by mutations in the ABCD1 gene. This rare genetic disorder leads to the buildup of very long-chain fatty acids, causing chronic progressive spastic paraplegia and difficulties with movement. The study aims to assess both the effectiveness and safety of dimethyl fumarate and to explore the molecular mechanisms underlying AMN. Participants will be randomly assigned to receive either dimethyl fumarate or a placebo daily for 36 months. For the first 24 months, some will take dimethyl fumarate while others take a placebo, after which all participants will receive dimethyl fumarate for the remaining 12 months. The drug is given orally at a dose of 480 mg per day, and the trial includes a triple-blind design to compare outcomes accurately. Participants will visit the clinic at the start, then at 3 months, 6 months, and every 6 months thereafter for checkups and tests including walking tests, strength assessments, and brain imaging. Researchers will monitor motor functions with postural sway tests over 36 months and will collect molecular data to understand disease mechanisms. The study includes detailed evaluations to track safety, adherence, and progression, with continued follow-up for a total participation period of 36 months.

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.

Adrenomyeloneuropathy (AMN) is a rare genetic disorder caused by mutations in the ABCD1 gene, leading to muscle weakness, reduced ankle joint movement, and nerve damage in the lower limbs. This condition causes a progression from increased muscle tone to paralysis, severely affecting walking and quality of life. Current treatments are limited, so researchers are exploring new options to improve symptoms and function in adults with AMN. This study evaluates spinal cord stimulation (SCS) as a potential treatment for lower limb muscle tone and movement problems in AMN patients. SCS involves implanting electrodes near the spinal cord and connecting them to a nerve stimulator that sends electrical pulses to stimulate nerves and improve motor function. After implantation, patients receive rehabilitation and use the stimulator regularly with specific schedules for continuous or intermittent stimulation. Participants will undergo preoperative evaluations followed by the implant surgery. They will then have scheduled assessments before and after starting stimulation at one week, four weeks, and follow-ups at four weeks and six months after hospital discharge. Researchers will measure walking ability, motor function, nerve signals, MRI scans, pain, and safety to understand the effects and risks of SCS in improving lower limb function in AMN patients over time.

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.