Giant Axonal Neuropathy

Researchers are studying the progression of rare genetic neurodegenerative disorders that affect the brain. This study aims to better understand how these diseases develop over time and how different interventions may impact their course. The conditions studied include a variety of specific disorders such as MLD, Krabbe Disease, ALD, MPS types, Batten Disease, and several others related to lysosomal storage and leukodystrophies. Participants will be observed through two main approaches: collecting information on the natural progression of these diseases (palliative care) and following patients who have received hematopoietic stem cell transplantation as part of their clinical care. Evaluations will be conducted by a multidisciplinary team at scheduled intervals—every 3 months during the first year, every 6 months in the second year, and annually thereafter. During the study, participants will undergo assessments of cognitive, language, gross motor, fine motor, and adaptive living skills development over a 15-year period. These evaluations will help track disease progression and the long-term effects of treatments. The study focuses on gathering detailed data to improve understanding of these rare conditions and support future care strategies.

Researchers are studying MELPIDA, a gene therapy aimed at treating Spastic Paraplegia Type 50 (SPG50), a rare inherited neurological disorder caused by mutations in the AP4M1 gene. SPG50 leads to progressive spasticity, intellectual disability, microcephaly, growth retardation, and severe cognitive impairment starting in infancy. The disease results in loss of motor functions, often leading to quadriplegia and wheelchair dependence by adolescence or early adulthood. There are currently no available treatments for SPG50, and this trial evaluates the safety and potential benefits of MELPIDA. MELPIDA delivers a fully functional human AP4M1 gene using a recombinant adeno-associated virus (AAV) serotype 9 via a single intrathecal injection. The study is an open-label Phase 1/2 trial assessing safety, tolerability, and exploring efficacy in children aged 4 months to 10 years with confirmed SPG50. The treatment targets neuronal cells to counteract neuronal loss associated with the disease. Participants will receive one dose of MELPIDA and be monitored for treatment-related adverse events and serious adverse events. During the study, participants will undergo regular assessments including clinical evaluations, neurological exams, and disease burden measurements. Safety monitoring will focus on identifying any treatment-related toxicities of Grade 3 or higher over a 60-month period. Researchers will track participants' ability to stand or walk, muscle tone, and cognitive function. Follow-up visits will include imaging and laboratory tests as needed to ensure safety and evaluate treatment effects. The trial aims to provide important data on MELPIDA’s safety and potential to improve outcomes for children living with SPG50.

This research focuses on early onset hereditary spastic paraplegia (HSP), a group of more than 80 inherited neurodegenerative diseases that cause progressive neurological decline and are the most common cause of inherited spasticity and disability. The study aims to define the clinical, imaging, and molecular characteristics of pediatric onset HSP to improve early diagnosis, counseling, and future treatment development. It also seeks to establish key outcome measures and gather data for clinical trials. Participants under the age of 30 who have early symptoms of HSP with a confirmed genetic variant or are relatives of someone diagnosed with HSP are enrolled. Biological samples such as skin, blood, or saliva will be collected and stored in a biorepository. Clinical and molecular data will be securely housed at Boston Children's Hospital and made available to approved investigators worldwide through a registry. During the study, researchers will collect longitudinal clinical data and patient-reported outcomes over about one year. They will establish the disease spectrum, track the natural history of early-onset HSP, and create a patient registry for future contact. The study involves ongoing documentation of clinical features, imaging, and molecular information to help identify biomarkers and therapeutic targets, with all data kept confidential and accessible only to authorized study staff and investigators.

Researchers are studying leukodystrophies and other genetic white matter disorders that affect the brain. These conditions have been difficult to diagnose, with many patients remaining undiagnosed for years despite extensive testing. The study aims to define new groups of patients with unclassified leukodystrophies, improve diagnosis using advanced genetic sequencing, understand disease mechanisms, and track the natural history and care of these disorders to help future research and treatment development. The project collects clinical data and biological samples from patients worldwide as part of the Myelin Disorders Biorepository Project, one of the largest collections of its kind. Participants include individuals with suspected or confirmed leukodystrophy or related brain white matter disorders, as well as healthy controls. The study involves ongoing data and sample collection to support multiple research goals, including discovery of new genetic causes and biomarkers. Participants provide clinical information, undergo standardized assessments, and may provide biological samples for research. Consent and assent are required. The study monitors participants over time to define disease progression and outcomes. The primary outcome is to identify novel homogeneous patient groups over a 10-year period. The long-term goal is to improve diagnosis, care, and future clinical trials for these rare disorders.

Researchers are evaluating the safety and effectiveness of the investigational drug ASO-GNAO1 (Tianasen) in children aged 1 to 14 years who have the c.607G>A mutation in the GNAO1 gene. This gene mutation is linked to epilepsy and neurodevelopmental disorders with progressive motor dysfunction and drug-resistant epilepsy. The study aims to see if ASO-GNAO1 can slow or stop the worsening of motor and cognitive symptoms and determine the right therapeutic dose. This is an open-label Phase 1/2 trial where all participants receive the active drug due to the rare and severe nature of the condition. Participants will receive escalating doses of ASO-GNAO1 through intrathecal injections over a 12-month period. The dose levels range from 0.3 mg/kg up to 1.5 mg/kg, administered as single doses per level. The drug works by specifically suppressing the mutant GNAO1 protein to potentially reduce disease progression. The dosing plan is based on preclinical studies and experience with similar personalized antisense therapies. No placebo control group is included. Throughout the study, children will undergo frequent neurological assessments, safety monitoring, biomarker testing, and other evaluations. Researchers will measure changes in monthly seizure frequency and duration, as well as the frequency and duration of non-epileptic hyperkinetic and dystonic episodes from baseline to week 50. The study also includes monitoring for any side effects or safety concerns during treatment and follow-up periods.