Giant Axonal Neuropathy

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.

This research aims to evaluate MELPIDA, a gene therapy for treating Spastic Paraplegia Type 50 SPG50, a rare inherited neurodegenerative disorder caused by mutations in the AP4M1 gene. SPG50 leads to progressive muscle stiffness, cognitive impairment, and severe disability starting in early childhood, with no current treatments available. The study focuses on safety and tolerability, as well as exploring effects on disease severity in affected children. MELPIDA delivers a functional copy of the AP4M1 gene using a single intrathecal injection of a recombinant adeno-associated virus AAV vector. The therapy targets neuronal cells to counteract neuronal loss caused by the disease. Participants will receive this gene therapy as the only treatment arm. The study follows an open-label design and lasts up to five years to assess long-term safety and potential clinical benefits. Participants will be closely monitored with evaluations including neurological exams and spasticity assessments using the Modified Ashworth and Tardieu scales. Safety will be measured by tracking adverse events related to treatment over 60 months. The trial includes genetic confirmation, clinical assessments, and long-term follow-up to understand the therapys impact on disease progression and patient health. Overall participation may extend up to five years.

Researchers are collecting long-term clinical data and biological samples from male and female patients under 30 who have early onset hereditary spastic paraplegia HSP. This neurodegenerative disorder causes progressive neurological decline and is the most common inherited cause of spasticity and disability. The study aims to better understand the diseases causes, clinical course, diagnosis, and treatment to support future research. Participants include those diagnosed clinically and genetically with HSP as well as their family members. The study involves building a registry and natural history database that documents clinical, imaging, and molecular features. Biological samples like blood, skin, and saliva will be collected to create a biorepository for molecular and cellular research. The registry and samples will be securely stored and shared with approved investigators worldwide. During participation, clinical and patient-reported outcome measures are collected over about one year to track disease progression. Researchers will use this data to define the disease spectrum, natural history, and meaningful endpoints for future trials. The study also supports early diagnosis, family counseling, and ongoing re-contact for research purposes. Participant involvement includes providing samples, clinical data, and follow-up information to help advance understanding of early onset HSP.

Researchers are collecting and analyzing clinical information and biological samples from people worldwide who have leukodystrophies, a group of genetic white matter brain disorders. The study aims to improve understanding of these diseases, find new genetic causes, develop biomarkers, and track the natural history of leukodystrophies to support future research and treatment development. This project is one of the largest biorepositories for leukodystrophy patients, with nearly 2,000 participants enrolled over more than ten years. Participants include individuals with suspected or confirmed leukodystrophies or related genetic white matter disorders, as well as healthy controls. The study involves collecting clinical data, standardized assessments, and biological samples to achieve multiple goals, such as defining new patient groups, evaluating next-generation genetic testing, understanding disease mechanisms, and following patients care and outcomes over time. Consent and assent are required for participation, and participants may be contacted for future studies. During the study, researchers gather clinical information, imaging data, and biological samples to track disease progression and care over a period of up to ten years from enrollment. The main outcome is to identify new homogeneous patient groups with unclassified leukodystrophies. Secondary outcomes include evaluating genetic testing methods, understanding disease biology, and maintaining contact with participants for ongoing research. Participation involves providing data and samples and completing assessments to help advance diagnosis and treatment for leukodystrophy patients globally.

Researchers are evaluating the investigational drug ASO-GNAO1 Tianasen in children with a specific GNAO1 gene mutation c.607G>A linked to epilepsy and neurodevelopmental disorder. This open-label study aims to determine if intrathecal ASO-GNAO1 can slow or stop the progression of motor and cognitive symptoms, assess its safety and tolerability, and find the appropriate therapeutic dose. The trial addresses a severe, progressive disease with no approved treatments, focusing on children who have drug-resistant epilepsy and movement disorders. Participants will receive escalating doses of ASO-GNAO1 through intrathecal injections over 12 months, starting at 0.3 mgkg and increasing every two weeks to a target dose of 1.2 mgkg, with the possibility of further increase to 1.5 mgkg if tolerated. After dose escalation, an interim analysis will evaluate pharmacokinetics, efficacy, and safety to decide on study continuation. All participants receive the active drug, with no placebo group due to the disease severity. Throughout the study, children will undergo frequent neurological exams, biomarker tests, and safety monitoring. Researchers will measure changes in seizure frequency and duration, as well as episodes of non-epileptic movement disorders, from baseline to week 50. Additional assessments include EEG activity, dystonia scales, motor function, developmental tests, and cognitive scores. The study duration and monitoring aim to capture detailed effects and safety data of the investigational treatment.