View clinical trials related to Adrenoleukodystrophy.
Filter by:A randomized open-label Phase 2a study to assess the pharmacokinetics and pharmacodynamic parameters of PXL770 after 12 weeks of treatment in male subjects with adrenomyeloneuropathy (AMN).
The investigators recently observed that up to 25% of women with X-linked adrenoleukodystrophy (ALD) have moderate to severe Restless Leg Syndrome (RLS). In this study, the investigators aim to estimate the prevalence of RLS among women with ALD and to assess whether pramipexole improves RLS symptoms as well as sleep and gait measures in women with ALD.
Subjects will be administered multiple doses of VK0214 in a cohort dose escalation process. A total of up to 36 subjects will be enrolled in the study, into one of three dose cohorts. For each cohort, up to 12 subjects will be randomized to receive VK0214 or placebo in a 3:1 ratio so that there will be a total of up to 9 subjects for each of the active doses and up to 3 subjects dosed with placebo in each cohort.
This study is a national, non-randomized, open-label, multi-site with minimal risk study in adult with adrenomyeloneuropathy (AMN), childhood and adult subjects with cerebral ALD (cALD), juvenile/adult metachromatic leukodystrophy (MLD) and adults with leukoencephalopathy and axonal spheroids and pigmented glia (ALSP). 49 subjects will be enrolled with one blood sample collection during one of their medical follow-up visit. This trial will evaluate the role of innate immunity to influence disease progression in X-ALD, MLD and ALSP, and if the mutations related to these leukodystrophies result in a specific immune response leading to the pathogenesis.
X-linked Adrenoleukodystrophy (X-ALD) is one of the most frequent inborn error of metabolism caused by mutations in the ABCD1 gene, which codes for the transporter of saturated very long-chain fatty acids (VLCFA) for peroxisomal degradation, thus causing their toxic accumulation in body fluids and tissues. The clinical spectrum ranges from adrenal insufficiency without neurological symptoms to a rapidly progressive, fatal cerebral demyelinating disease that may occur in childhood as well as later in life. The most frequent phenotype in adulthood is adrenomyeloneuropathy (AMN), a slowly progressive myelopathy and peripheral neuropathy, which may also be prevalent in up to 80% of females carrying the X-ALD gene defect. Since signs and symptoms in females are usually milder and with a later onset, they are frequently underestimated, overlooked or misinterpreted, e.g. as Multiple Sclerosis. Consequently, many women with X-ALD do not receive adequate treatment. Against this background, the development of new therapeutic interventions with the help of eHealth technology (e.g., counselling and treatment via digital communication tools) is of particular relevance, as it provides cost-effective, regular care even for patients who live remote from Leukodystrophy clinics. The aims of this study is to evaluate the effectiveness of a multi-approach intervention ("SMART-ALD") on physical and mental well-being and quality of life in n=30 X-ALD symptomatic heterozygous females compared to a waiting list control group (n=30) using electronic health (ehealth) technology.
X-linked adrenoleukodystrophy (X-ALD) is a hereditary white matter disorder caused by mutations in the ABCD1 gene leading to disturbances in the metabolism of fatty acids. This results in an accumulation of very long chain fatty acids (VLCFA) in the cells of the body causing damage to the central nervous system (white matter of the brain and spinal cord). The most common adult-onset X-ALD phenotype is adrenomyeloneuropathy (AMN), a slowly progressive myelopathic variant with demyelination of the long tracts in the spinal cord, clinically manifested as slowly progressive spastic paraparesis, sensory ataxia, bladder and sexual dysfunction. Although this rare disease is inherited X-linked, previous research revealed that up to 80% of heterozygous women develop AMN symptoms during their lifetime. The primary objectives of this study are 1) to assess the prevalence of symptomatic courses in female carriers of X-ALD and 2) to determine the impact of AMN symptoms on the quality of life of affected women in various areas (including everyday life, work, social network, sleep quality, sexuality, mood). Participants are asked to fill in self-report questionnaires, which are available in English, German, French, Spanish, and Italian, and are provided electronically on the online platform Leuconnect (https://www.leuconnect.com) launched by European Leukodystrophies Association (ELA) international (https://elainternational.eu/).
An Open-Label, multicenter study in male pediatric patients with cerebral x-linked adrenoleukodystrophy (cald) to assess the effects of MIN-102 treatment on disease progression prior to human stem cell transplant (HSCT)
Adrenoleukodystrophy (X-ALD) is the most common genetic disorder of the brain white matter with an incidence of 1:14,700 births. It is caused by mutations in the ABCD1 gene, which encodes a transporter of very long-chain fatty acids (VCLFA) into the peroxisome for degradation. As a consequence VLCFA accumulate in tissues and plasma being the pathognomonic biomarker for diagnosis. The excess of VLCFA produces mitochondrial ROS and oxidative damage, a major factor driving X-ALD pathogenesis. Other key dysregulated pathways are energy production, mitochondrial biogenesis and respiration, proteostasis, and ER stress. Current therapeutic options are unsatisfactory, restricted to bone marrow transplant and gene therapy, for which most patients do not qualify. The encouraging results of plasma exchange (PE) with albumin replacement for Alzheimer's Disease prompted us to start this study. Our rationale is the following: In plasma, VLCFA are transported by lipoproteins and albumin. Albumin is the major transporter of fatty acids (FA) to the brain. ABCD1 deficiency induces inflammation and increases blood-brain barrier leakage, which could facilitate increased permeability to albumin. We posit that replacement of albumin would lower VLCFA levels in plasma through peripheral sink mechanisms, diminishing the quantity of VLCFA reaching the brain, and would prevent lipid peroxidation. A pilot proof-of-concept study in 5 X-ALD patients will be carried out to replace endogenous albumin through PE applied, once a week the first month and monthly for 5 months. A 6 months follow-up after the end of the treatment will be carried out.
In the early years of life and during adolescence, physical activity is crucial for good development of motor skills. It is even more so for those children and young people who are forced to undergo anti-cancer therapies and therefore undergo long periods of hospitalization (often bedridden) and prolonged periods of physical inactivity. The research project "Sport Therapy" was born with the aim of demonstrating that, through targeted physical activity administered by the sports physician in collaboration with the pediatrician hematologist, it is possible to facilitate the full recovery of these patients, avoiding the high risk of chronic diseases related to a sedentary lifestyle and allowing them to better reintegrate, once healed, in their community of origin (school, sport and social relations). The research project "Sport Therapy" was born within the Maria Letizia Verga Center at the Pediatric Clinic of the University of Milan Bicocca, at the Foundation for the Mother and Her Child, San Gerardo Hospital in Monza. Every year, around 80 children and adolescents with leukemia, lymphoma or blood disorders leading to bone marrow transplantation are treated here.
X-linked adrenoleukodystrophy is a rare, demyelinating and neurodegenerative disorder, due to loss of function of a fatty acid transporter, the peroxisomal ABCD1 protein. Its more frequent phenotype, the adrenomyeloneuropathy in adults, is characterized by axonal degeneration in spinal cord, spastic paraparesis and a disabling peripheral neuropathy. Actually, there is no efficient treatment for the disease. The work of the researchers in the last twelve years dissecting the physiopathological basis of the disorder has uncovered an involvement of the early oxidative stress in the neurodegenerative cascade and mitocondrial depletion. In a preclinical trial they have observed that pioglitazone, a PPARγ/PGC-1α axis metabolic activator with immunomodulatory, anti-inflammatory and antioxidant response regulator properties, efficiently reverse the clinical symptoms and the axonal degeneration in the mouse model for the disease and normalize stress and mitochondrial depletion biomarkers. The researchers will test the effectiveness of the drug in terms of motor function and correction of oxidative damage markers in proteins and DNA and inflammation markers in an open trial. Fifteen-twenty patients will be included and clinically explored and assessed in the HU of Bellvitge and the HU of Donostia using clinical scales for spasticity, evoked potentials, electroneurinograms and cranial RMN. The information will be collected in a data base that will be of great value to improve the present attention and the future follow-up of the patients and to facilitate their inclusion in therapeutic randomized, double blind, against placebo, multicentric and international clinical trials.