The aim of this study is to treat the signs and symptoms of late infantile neuronal ceroid lipofuscinosis (LINCL), a fatal inherited disease in the brain. This will be accomplished by using delivery of a gene (method called gene transfer) to administer to the brain an experimental drug called AAV2CUhCLN2, a gene transfer vector.

Condition	Intervention	Phase
Batten Disease Late Infantile Neuronal Lipofuscinosis	Gene Transfer: AAV2CUhCLN2  Procedure: Neurosurgery	Phase I

Further Study Details: 

Primary Outcomes: The primary endpoint for the trial is neurological assessment using the LINCL clinical rating scale at screening; pre-therapy; and 6 and 18 months post-vector administration.
Secondary Outcomes: The secondary endpoint variable will be the MRI/MRS assessment of the CNS in regions of vector administration. This will be assessed at screening; pre-therapy; and 6 and 18 months post-vector administration.
Expected Total Enrollment:  11

Late infantile neuronal ceroid lipofuscinosis (LINCL) is a fatal childhood neurodegenerative lysosomal storage disease with no known therapy. There are estimated to be 200 to 300 children in the USA at any one time with the disease. LINCL is a genetic disease resulting from mutations in the CLN2 gene. The CLN2 gene encodes a protein tripeptidyl peptidase-I (TPP-I) which is absent/deficient in children with LINCL. This absence/deficiency of TPP-I results in lysosomal storage and subsequent cell death (especially neurons). The children with LINCL are chronically ill, with a progressive CNS disorder that invariably results in death, typically by age 8 to 12.

This clinical study will evaluate the concept that persistent expression of the normal CLN2 cDNA in the CNS will result in the production of sufficient amounts of TPP-I to prevent further loss of neurons, and hence limit disease progression. To assess this concept, an adeno-associated virus vector encoding the normal human CLN2 gene (AAV2CUhCLN2) will be used as a vehicle to deliver and express the human CLN2 cDNA in the brain of children with LINCL. The proposed study will include 11 individuals and will be divided into two parts. Group A, to be studied first, will include 5 individuals with the severe form of the disease. Group B of the trial will include 6 individuals with a moderate form of the disease. Following direct intracranial administration of the vector, there will be neurological assessment using the LINCL clinical rating scale and magnetic resonance imaging/magnetic resonance spectroscopy assessment of the CNS in regions of vector administration. The data generated will help evaluate two hypotheses: (1) that it is safe to carry out direct intracranial administration of the AAV2CUhCLN2 vector to the CNS of individuals with LINCL; and (2) that administration of the AAV2CUhCLN2 vector will slow down or halt the progression of the disease in the central nervous system.

Ages Eligible for Study:  3 Years   -   18 Years,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria:

• A definitive diagnosis of late infantile neuronal ceroid lipofuscinosis
• Between the age of 3 and 18 years
• Not previously participated in a gene transfer study for LINCL.
• 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.
• Both parents or legal guardians must give consent for their child’s participation in the research study.

Exclusion Criteria:

• Other significant medical or neurological conditions may disqualify the patient from participation in this study, particularly those which would create an unacceptable operative risk or risk to receiving the AAV2CUhCLN2 vector.
• Individuals with heart disease that would be a risk for anesthesia.
• History of hemorrhage or major risk factors for hemorrhage
• Concurrent participation in any other FDA approved Investigational New Drug clinical protocol is not allowed, although the Principal Investigator will work with other doctors to accommodate specific requests (e.g., a study of nutritional supplements probably would not be a disqualification).
• Individuals who have a (1) heart pacemaker and/or related implants, (2) metal fragment/chip in the eye or other sites, (3) an aneurysm clip in their brain, and (4) metallic inner ear implants.

Please refer to this study by ClinicalTrials.gov identifier  NCT00151216

Stephanie Bangs, BA      212-746-5310    scb2006@med.cornell.edu
Charleen Hollmann, PhD, RN      212-746-5310    chollman@med.cornell.edu

New York
      New York Presbyterian Hospital - Weill Medical College of Cornell University, New York,  New York,  10021,  United States; Recruiting

Study chairs or principal investigators

Ronald G. Crystal, MD,  Principal Investigator,  Weill Medical College of Cornell University   

Study ID Numbers:  WMC 0401007010; OBA-RAC 0312-619
Last Updated:  September 7, 2005
Record first received:  September 6, 2005
ClinicalTrials.gov Identifier:  NCT00151216
Health Authority: United States: Food and Drug Administration; United States: Institutional Review Board
ClinicalTrials.gov processed this record on 2005-09-13