Adrenoleukodystrophy (ALD)

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 Addenbrookes 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 physicians guidance at the UPMC Childrens 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.

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 participants 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 therapys impact on the disease course and participants neurological function.

Researchers are studying the progression of rare genetic neurodegenerative disorders that affect the brain. This research aims to better understand how these diseases develop over time and to analyze the effects of different interventions. The study is observational and focuses on disorders such as MLD, Krabbe Disease, ALD, and many other rare conditions affecting the nervous system. Participants are observed without receiving experimental treatments. The study collects data from patients who are receiving standard care, including those who have undergone Hematopoietic Stem Cell Transplantation HSCT and those receiving palliative care. Evaluations by a multidisciplinary team occur regularly every 3 months during the first year, every 6 months in the second year, and once a year thereafter. During these visits, researchers assess key developmental areas including cognitive, language, gross and fine motor skills, and adaptive living skills over a 15-year period. Brain neurodegeneration is monitored using MRI diffusion tensor imaging in patients from birth to 5 years old, while exploratory biomarkers are also collected. This long-term follow-up helps track disease course and intervention outcomes for up to 15 years.

Researchers are studying adults and children affected by several inherited brain diseases including adrenomyeloneuropathy AMN, cerebral adrenoleukodystrophy cALD, metachromatic leukodystrophy MLD, and adult-onset leukoencephalopathy with axonal spheroids and pigmented glia ALSP. These conditions involve nerve damage and inflammation, and the study aims to understand how immune cells called macrophages contribute to disease progression. This observational study involves 49 participants and explores how genetic mutations affect immune responses linked to these diseases. Participants include affected children and adults as well as healthy controls. The main activity involves collecting one blood sample during a routine medical visit. This sample will be used to analyze macrophage function, including their ability to engulf myelin, their distribution, and certain immune markers. No treatments or interventions are given, as this is a minimal risk study focusing on immune system activity related to these conditions. During the study, researchers will monitor macrophage function and gene activity over a two-year period following blood collection. Participants will have one blood draw during their scheduled medical follow-up. The study also includes healthy children and adults for comparison. The research team will track immune cell profiles and metabolic patterns to better understand how immune responses may influence disease outcomes in these leukodystrophies.