Batten Disease

Researchers are evaluating TTX-381, a gene therapy, in a first-in-human, open-label study to treat eye problems caused by Neuronal Ceroid Lipofuscinosis Type 2 (CLN2), also known as Batten disease. This condition results from a faulty gene causing lack of an important enzyme, leading to damage in the brain, spinal cord, and eyes, affecting vision and other functions. The study aims to understand the safety and tolerability of TTX-381 to address these ocular issues in affected children. Participants will receive a single dose of TTX-381 injected under the retina of one eye, while the other eye will serve as a control for comparison. The study includes several dose levels, such as 2×10^10 and 6×10^10 genome copies per eye, with an expansion group receiving the lower dose as determined by an independent committee. This dose-escalation design helps researchers monitor effects at different doses and assess safety. During the five-year follow-up, participants will have regular assessments including eye scans to measure retinal thickness and damage areas, testing for the gene therapy product in eye fluid, and monitoring for any side effects or adverse events. The study team will also collect urine and tear samples to evaluate shedding of the therapy. Safety and eye health will be closely observed throughout the study to gather comprehensive data on the treatment's impact.

Researchers are investigating the frequency of Neuronal Ceroid Lipofusinosis Type 2 (CLN2) in children aged 2 to 6 years who have nonspecific neurological symptoms such as idiopathic seizures, speech disorders, and motor dysfunctions. This multicenter, non-drug screening study focuses on children without hypoxic ischemic encephalopathy, head trauma, or developmental brain anomalies, aiming to better understand the demographic and clinical features of those with possible CLN2 disease. Children first undergo assessments including recording demographic and medical history, seizure frequency, cognitive and language development evaluations, physical exams assessing muscle strength, gait, and coordination, as well as neurological evaluations using EEG and MRI scans. Those showing specific signs like speech disorder with seizures, movement problems, particular EEG responses, or MRI findings will have blood samples taken to measure Tripeptidyl Peptidase 1 enzyme levels. If enzyme activity is low, genetic testing is performed to investigate CLN2 disease. Participants are involved for up to one year during which various clinical, neurological, and imaging evaluations are done. Blood samples are collected for enzyme and genetic analyses. The main outcome measured is the frequency of CLN2 disease in this group. The study tracks each child's symptoms, neurological findings, and imaging results to better identify and understand CLN2 in children with these symptoms.

Researchers are evaluating the safety and effectiveness of ION283, an anti-sense oligonucleotide therapy given by injection into the spinal fluid through a lumbar puncture, in patients aged 10 to 18 years with Lafora disease. This open-label Phase 1/2 study aims to understand how well multiple doses of 15 mg ION283 work and how safe they are for these patients over a period of two years. Participants will receive an initial dose of 15 mg ION283 as an intrathecal bolus injection every 12 weeks during the 24-month open-label treatment period, following a 4-week screening period. All enrolled subjects will receive the same dose and treatment without placebo or comparison groups. Throughout the study, participants will undergo assessments including clinical evaluations, seizure frequency monitoring, and several quality of life and disability scales at baseline and after two years. Safety will be closely monitored by tracking treatment-related adverse events, and various EEG recordings will be used to assess changes in brain activity. Participants are expected to comply with study requirements for up to two years.

Researchers are exploring how the stress of caregiving affects the health and well-being of adults who care for people with chronic medical conditions. This observational study aims to understand the social, psychological, behavioral, and biological factors involved in caregiving over time, including during and after the death of the care recipient. The study includes caregivers of various chronic conditions such as inherited metabolic disorders, undiagnosed diseases, Batten's disease, Tay Sachs, and diabetes. Participants may be grouped as active caregivers or bereaved caregivers who have lost their care recipient. Over one year, and possibly up to five years, participants will complete online surveys about their health, caregiving experiences, and social support networks. They will also take part in two-part phone interviews about their caregiving and social connections. Some may keep a diary every three months to record daily social activities, stress, and feelings. Blood samples may be collected annually for biological analysis. During the study, participants will provide information through surveys, interviews, and diaries, with some giving yearly blood samples. Researchers will assess changes in social, psychological, behavioral, and biological factors related to caregiving. The primary outcome is to track the natural history of caregiver stress over time. Participation involves various tasks and assessments done online or by phone, with follow-ups possible for up to five years to understand long-term effects.

Researchers are investigating the natural history of Batten disease, also known as Neuronal Ceroid Lipofuscinosis, a genetic disorder that causes progressive cognitive and behavioral decline in children and adults. The study aims to gather detailed information about the motor, behavioral, and functional abilities of people with Batten disease and to improve the Unified Batten Disease Rating Scale (UBDRS), a clinical tool designed to measure disease severity and progression. Participants with any form of Batten disease will be assessed using the UBDRS approximately once a year for up to 20 years. The study involves clinical and neuropsychological evaluations, including cognitive and behavioral assessments, adaptive function, quality of life measures, and vision tests. Assessments may take place at the University of Rochester Batten Center, annual meetings of the Batten Disease Support and Research Association, or remotely through televideo. During their involvement, participants will provide medical history, symptom details, medication use, and diagnostic test information. Researchers will monitor changes in physical health, seizures, behavior, and function annually using the UBDRS, along with cognitive and vision-related measures. The study may last up to 20 years, with some assessments continuing for up to 10 years, and aims to better understand disease progression and its impact on daily life.

Researchers are studying people affected by rare inherited retinal degenerative diseases through the My Retina Tracker Registry. Sponsored by the Foundation Fighting Blindness, this observational study aims to better understand the diversity, prevalence, and natural history of these diseases and gene variants. It also seeks to support research and clinical trials by collecting detailed patient and clinical information over time. Participants create an online profile via a secure portal where they share their own perspective on their retinal disease, including family history, genetic test results, and general health. They can also invite their clinicians to add clinical exam data after each visit to build a comprehensive longitudinal record. The registry uses standardized data entry to maintain consistency and allows participants to compare their data with others. During the study, participants regularly update their profiles with personal and clinical information. Researchers measure the number of participants with rare diagnoses within the inherited retinal degenerative disease category, tracking data for up to 20 years. The registry supports recruitment for research while protecting patient privacy. Participation involves ongoing data entry and clinical updates, contributing to a better understanding of these rare eye diseases.

Researchers are studying Juvenile Neuronal Ceroid Lipofuscinosis (CLN3), also known as Batten disease, a genetic disorder that causes decline in brain and nervous system functions affecting vision, thinking, movement, and sometimes causing seizures. Symptoms usually start between ages 4 and 7, and there are currently no effective treatments. The study aims to find clinical and biochemical markers that can be used to measure treatment outcomes and to better understand the disease for future therapies. Participants include individuals diagnosed with CLN3 or related conditions as well as their family members. They will provide various biological samples such as spinal fluid, blood, urine, and skin, and may also contribute medical records or photos. Multiple healthcare specialists will evaluate them, and collected samples may be shared with other researchers for testing, with privacy protections in place. During the study, participants will undergo assessments to collect baseline and progression data on clinical and biochemical markers. Researchers will establish a biorepository of samples for future research. The study will monitor tolerability and feasibility of assessments and aims to provide tools for future therapeutic trials. Participation may involve yearly follow-ups, and the study is ongoing with no fixed end date.

Researchers are establishing the Italian NCL Registry to systematically collect and manage data from patients affected by neuronal ceroid lipofuscinosis (NCLs). This observational study aims to support research and the development of future clinical trials by capturing the complex characteristics of NCL through detailed clinical assessments, validated scales, biomarkers, and patient-reported outcomes. The study is coordinated by IRCCS Fondazione Stella Maris and involves multiple clinical centers in Italy. Participants will be assessed annually at one of three clinical sites, where they will undergo comprehensive clinical and neurological examinations, including the use of illness scales such as the Hamburg scale and UBDRS, and questionnaires on psychiatric symptoms, sleep disorders, and quality of life. Biological samples like blood, urine, or tissue may be collected and stored for further analysis. Additional diagnostic tests, including optical coherence tomography, brain MRI, and neurophysiology, performed as part of routine clinical care, will also be recorded. Throughout the study, data collected from clinical evaluations, laboratory tests, and imaging will be entered into the registry in a pseudonymized form to protect patient privacy. Follow-up visits every 12 months will monitor disease progression, allowing comparison across patient groups based on factors like phenotype, genotype, or age at onset. The primary outcome is the establishment of the registry to document the natural history and clinical presentation of NCL over time, supporting ongoing research and potential future therapies.

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 understand the natural history and progression of Neuronal Ceroid Lipofuscinoses (NCL), also known as Batten disease, which are rare inherited neurodegenerative disorders caused by mutations in various genes. These mutations lead to progressive loss of motor skills, cognition, vision, seizures, and behavior changes. The study seeks to document symptom development and disease progression more accurately to support testing of new experimental treatments and improve scientific knowledge. Participants include patients with genetically confirmed NCL diagnoses, covering multiple gene mutations such as CLN1 through CLN14. The study collects data through medical records, patient questionnaires, and routine clinical exams focused on motor, language, cognition, seizures, vision, and behavior. A local biorepository and an international virtual biorepository are established to facilitate access to patient samples for research. Families of deceased patients with known genetic mutations may also contribute retrospective data. During participation, researchers gather clinical information over time to identify key symptoms and develop tools for rating disease progression, with follow-up lasting up to 30 years. This includes establishing well-characterized natural history cohorts to serve as controls for future therapy trials. The study also collects and stores biological samples to support international research efforts. There is no treatment involved; instead, the focus is on observation and data collection to better understand NCL diseases.