Active clinical trials for "Neuronal Ceroid-Lipofuscinoses"

Patients with infantile or late infantile NCL have either a reduced amount of, or are missing, the palmitoyl protein thioesterase 1 (PPT1) enzyme or the tripeptidyl peptidase 1 (TPP-I) enzyme. Human central nervous system stem cells (HuCNS-SC) are an investigational product derived from human brain cells. HuCNS-SC have been shown to survive and migrate within the brains of mice. When grown in the laboratory, HuCNS-SC have been shown to produce the PPT1 and TPP-I enzymes. In mice missing the PPT1 enzyme, HuCNS-SC have been shown to increase the amount of this enzyme in the brain, to reduce the amount of abnormal storage material in the brain, and to prevent the death of some neurons (a type of cell) in the brain. Participation in this study will involve screening assessments, surgery to implant HuCNS-SC, medication to suppress the immune system, and a series of follow-up assessments. The length of time from the start of screening through to the last follow-up visit will be approximately 13 months, with frequent visits to the study center during this time. After completion of this study, patients will be monitored for an additional 4 years under a separate long term follow-up protocol.

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.

The Phase 1/2 study (190-201) evaluated the efficacy and safety of a 300 mg dose of BMN 190 administered every other week (qow) to patients with CLN2. The dose and regimen for this study (190-202) are based on the results of the 190-201 study. The rationale for this phase 2 extension study is to provide patients who complete the 190-201 study with the option to continue BMN 190 treatment. The 190-202 study is an open label extension protocol to assess long-term safety and efficacy.

The investigators propose to assess the safety and efficacy of a new administration method to deliver a biologic to children with a form of Batten disease using an experimental gene transfer procedure. This gene transfer procedure consists of delivering a good copy of the mutated gene to the nerve cells via a virus. These children are born with genetic changes called mutations that result in the inability of the brain to properly recycle proteins. The recycling failure leads to death of the nerve cells in the brain and progressive loss of brain function. Children with Batten disease are normal at birth but by age 2 to 4 have motor and vision problems which progress rapidly to death at age approximately 10 years old. There are no therapies available to treat the disease. The investigators previous clinical trial used a virus called adeno-associated virus 2 (AAV2) as the gene delivery system. That study showed that viral delivery of the gene was safe and showed small, but significant benefits to the recipient. The investigators currently have an IRB approved protocol which uses a slightly different virus called AAVrh.10 as the gene delivery system. This 3rd protocol proposes to use the same virus AAVrh.10 as the gene delivery system and has expanded the eligibility criteria.

The purpose of this study is to determine the safety and engraftment of donor hematopoietic cells using this conditioning regimen in patients undergoing a hematopoietic (blood forming) cell transplant for an inherited metabolic storage disease.

This Phase 2 open-label, multicenter study will evaluate the safety, tolerability, and efficacy of BMN 190 intracerebroventricular (ICV) administration every other week (qow) for a period of 144 weeks, in patients with CLN2. The study is designed to assess disease progression in CLN2 patients treated with BMN 190 compared to natural history data from untreated historical controls.

This study will examine the effectiveness of a drug called Cystagon in treating infantile neuronal ceroid lipofuscinosis (INCL), a progressive neurological disease affecting children. At around 11 to 13 months of age, patients develop slowed head growth, mild brain atrophy (wasting), electroencephalographic (EEG) changes and retinal deterioration, with symptoms worsening over time. The disease results from an enzyme deficiency that causes fatty compounds called ceroid to accumulate in cells. In laboratory experiments, Cystagon has helped remove ceroid from cells of patients with INCL. Children with INCL between 6 months and 3 years of age may be eligible for this study. Participants take Cystagon daily by mouth every 6 hours. They are admitted to the NIH Clinical Center for a 4- to 5-day period every 6 months for the following tests and evaluations: Review of medical history, including a detailed record of seizures, physical examination, blood tests and clinical photographs. For the initial baseline studies, examinations may also be scheduled with pediatric neurology, ophthalmology and anesthesia services. Magnetic resonance imaging (MRI) of the brain MRI uses a powerful magnet, radio waves, and computers to provide detailed images of the brain without the use of X-rays. The patient lies on a table that slides inside a donut-shaped machine containing a magnetic field. The child requires general anesthesia for the procedure. Electroretinogram (ERG) measures the function of the retina, the light-sensitive tissue in the back of the eye. To record the flash ERG, a special contact lens is placed on the eye s surface and the eye is stimulated with flashes of light. Infants and very young children require general anesthesia for the procedure. Visual evoked potential (VEP) measures the function of the visual pathway from the eye to the brain. To record the VEP, five electrodes are placed on the scalp and the eye is stimulated with flashes of light. Infants and very young children must be anesthetized for the procedure. Electroencephalogram (EEG) measures brain electrical activity, using electrodes placed on the scalp. The test is useful in defining seizures. The child may need to be sedated to keep still during the test. Skin biopsy A small piece of skin is removed (usually from the upper arm or shoulder) under local anesthetic to grow cells in the laboratory. This procedure is done at the start of the study and is repeated after 1 year if therapy results are promising. Children s condition may improve, stabilize or worsen during this study. Life may be prolonged without significant improvement in quality. The information gained from the study may help scientists develop more potent drugs to treat INCL.

This is a proposed follow up study on the investigators previous gene transfer human clinical trial entitled "Administration of a Replication Deficient Adeno-associated Virus Gene Transfer Vector Expressing the Human CLN2 cDNA to the Brain of Children with Late Infantile Neuronal Ceroid Lipofuscinosis" (Weill Cornell IRB# 0401007010). As in the previous study, the investigators propose to administer a biologic by direct gene transfer into the brain and assess its safety on children with a fatal genetic disease of the central nervous system (CNS). The disease is Late Infantile Neuronal Ceroid Lipofuscinosis (LINCL, a form of Batten disease). This will be accomplished by using delivery of a gene (method called gene transfer) to administer to the brain an experimental drug called AAVRh.10CUhCLN2, a gene transfer vector.

The primary objective of this trial is to establish the safety and tolerability of short-term (8 weeks) administration of mycophenolate mofetil in ambulatory children with JNCL. The secondary objective is to gather preliminary evidence of the short-term (8 week) impact of mycophenolate mofetil on clinically relevant features of JNCL as measured by the Unified Batten Disease Rating Scale (UBDRS), including motor features, seizures, behavior, cognitive and functional measures. Funding source-FDA Office of Orphan Product Development (OOPD).

This is a phase 1/2, open-label, single dose study to evaluate the safety and efficacy of AT-GTX-501 delivered intrathecally into the lumbar spinal cord region of participants with mild to moderate variant late infantile neuronal ceroid lipofuscinosis associated with mutation(s) in the CLN6 gene (vLINCL6 disease).