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.

Researchers are evaluating MELPIDA, a gene therapy product, for treating Spastic Paraplegia Type 50 (SPG50), an ultra-rare genetic disorder causing progressive neurodegeneration, spasticity, intellectual disability, and severe motor impairment. SPG50 results from mutations in the AP4M1 gene, leading to loss of function in the adaptor protein complex 4, which affects critical protein trafficking in neuronal cells. This trial aims to assess the safety and tolerability of a single intrathecal dose of MELPIDA and explore its effects on disease burden in affected children. The study involves administering MELPIDA, which delivers a functional human AP4M1 gene via a recombinant adeno-associated virus (AAV9) through an injection into the spinal canal. This is an open-label, phase 1/2 trial focusing on a single treatment dose. Participants are children aged 4 months to 10 years with confirmed SPG50. The trial monitors safety by tracking treatment-related adverse and serious adverse events, while also evaluating efficacy through measures of spasticity using the Modified Ashworth and Tardieu scales over a 60-month period. Participants will be closely observed for up to five years after treatment to monitor any toxicities or changes in spasticity and disease progression. Assessments include clinical exams and neurological evaluations to measure motor function and spasticity levels. Safety monitoring involves tracking laboratory values and any adverse events. The long follow-up allows researchers to gather detailed information on the treatment's impact over time and the natural course of SPG50 in treated children.

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 disease's 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 mg/kg and increasing every two weeks to a target dose of 1.2 mg/kg, with the possibility of further increase to 1.5 mg/kg 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.