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This study evaluates a gene therapy (delivering the CLN2 gene to the brain via an AAVrh.10 vector) in children with Late Infantile Neuronal Ceroid Lipofuscinosis (LINCL, a type of Batten disease). It included children with a diagnosis confirmed clinically and genetically (CLN2 mutation). It was a Phase 1 study and has been completed.
The summary above is a plain-language rendering of the official record. The original English title is shown for reference.
Criteria are reproduced from the ClinicalTrials.gov record in the original English. Only the trial team can determine eligibility.
Inclusion Criteria: All individuals who meet the following criteria will be included without bias as to a gender or race/ethnicity. Each case will be individually reviewed with the Eligibility Committee comprised of 3 physicians other than the PI, including a pediatric neurosurgeon, pediatric neurologist and general pediatrician. 1. Definitive diagnosis of LINCL, based on clinical phenotype and genotype. The genotype must include at least one of the 5 most common CLN2 mutant genotypes: C3670T (nonsense Arg208 to stop), G3556C (intron 7 splice), G5271C (Gln422His), T4396G (aberrant splicing, intron 8) and G4655A (Cys365Tyr). If either parental allele is R447H, the patient will not be included in the study. These account for a total of 83% of the mutations in the study by Sleat et al and 82% of the mutations in our studies. The study does not limit to one specific genotype (genetic constitution) since our data regarding the natural history of the disease and the studies of Steinfeld, show that, for these 5 genotypes (genetic constitution), LINCL subjects have similar clinical course. 2. The subject must be between the age of 2 and 18 years. 3. Subjects will have an average total score of 4 - 12 on the Weill-Cornell LINCL scale, and the total score should not be outside the 95th percentile confidence limits for age based on our historic data. 4. The subject will not previously have participated in a gene transfer or stem cell study. 5. Parents of study participants must agree to comply in good faith with the conditions of the study, including attending all of the required baseline and follow-up assessments, and both parents or legal guardians must give consent for their child's participation. 6. Sexually active subjects will have to use contraception during the treatment and for 2 months after completion of the treatment. 7. If asymptomatic (i.e - An LINCL score of 12), has one older sibling who has a positive genotype and has clinical manifestations of the disease. Exclusion Criteria: 1. Presence of other significant medical or neurological conditions may disqualify the subject from participation in this study, particularly those which would create an unacceptable operative risk or risk to receiving the AAVrh.10CUhCLN2 vector, e.g., malignancy, congenital heart disease, liver or renal failure. 2. Subjects without adequate control of seizures. 3. Subjects with heart disease that would be a risk for anesthesia or a history of major risk factors for hemorrhage. 4. Subjects who cannot participate in MRI studies. 5. Concurrent participation in any other FDA approved Investigational New Drug. 6. Subjects with history of prolonged bleeding or abnormal platelet function or taking aspirin. 7. Renal disease or altered renal function as defined by serum creatinine \> 1.5 mg/dl at admission. 8. Abnormal serum sodium, potassium calcium, magnesium, phosphate at grade III or IV by Division of AIDS Toxicity Scale. 9. Hepatic disease or altered liver function as defined by SGPT \> 150 U/L, and or Total Bilirubin \> 1.3 mg/dL 10. Immunosuppression as defined by WBC \< 3,000/µL at admission 11. Uncorrected coagulopathy during the baseline period defined as INR \> 1.4; PTT \> 35 sec; PLT \< 100,000/mm3. 12. Anemia (hemoglobin \< 11.0 g/dl at \> 2 years of age, with normal serum iron studies).