Cystagon to Treat Infantile Neuronal Ceroid Lipofuscinosis

2014-08-27 03:56:26 | BioPortfolio


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.


Neuronal ceroid lipofuscinoses (NCLs), commonly known as Batten disease, represent a group of the most common (1 in 12,500) heritable neurodegenerative storage disorders of childhood. Mutations of at least 8 different genes are responsible for various forms of NCL. The infantile form of NCL or INCL is the most severe disease. It is caused by mutations in the palmitoyl-protein thioesterase-1 (PPT1) gene. PPT1 is a lysosomal enzyme that cleaves thioester linkages in S-acylated proteins and its deficiency leads to abnormal lysosomal accumulation of fatty-acylated-proteins (ceroids) leading to INCL pathogenesis. Since thioester linkages are labile, drugs with nucleophilic property are likely to mimic PPT1 and may have therapeutic potential for INCL. We previously reported that cysteamine, phosphocysteamine, cysteamine bitartrate and N-acetylcysteine disrupt thioester linkages in a model PPT1-substrate, [14C] palmitoyl~CoA, releasing [14C] palmitic acid. The results of our laboratory studies have shown that cysteamine mediates the depletion of intracellular ceroid deposits and prevents their reaccumulation. For the last 8 years, we have been conducting a clinical trial to determine whether Cystagon (Cysteamine bitartrate) is beneficial for INCL patients. In parallel with these studies, using an animal model of INCL we found that there is high level of reactive oxygen species (ROS) generated in the brain of mice lacking the PPT1 enzyme. ROS has been shown to cause damage to normal neurons. Both Cystagon and mucomyst in addition to possessing nucleophilic property are antioxidants and scavengers of ROS. Thus, in our current protocol we use a combination of Cystagon and Mucomyst. We admitted a total of 10 patients (5 females and 5 males) to this protocol.

Study Design

Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment


Infantile Neronal Ceroid Lipofuscinosis




National Institutes of Health Clinical Center, 9000 Rockville Pike
United States




National Institutes of Health Clinical Center (CC)

Results (where available)

View Results


Published on BioPortfolio: 2014-08-27T03:56:26-0400

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Medical and Biotech [MESH] Definitions

A heterogeneous group of primarily familial disorders characterized by myoclonic seizures, tonic-clonic seizures, ataxia, progressive intellectual deterioration, and neuronal degeneration. These include LAFORA DISEASE; MERRF SYNDROME; NEURONAL CEROID-LIPOFUSCINOSIS; sialidosis (see MUCOLIPIDOSES), and UNVERRICHT-LUNDBORG SYNDROME.

A group of severe neurodegenerative diseases characterized by intracellular accumulation of autofluorescent wax-like lipid materials (CEROID; LIPOFUSCIN) in neurons. There are several subtypes based on mutations of the various genes, time of disease onset, and severity of the neurological defects such as progressive DEMENTIA; SEIZURES; and visual failure.

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A voltage-gated sodium channel subtype that mediates the sodium ion permeability of excitable membranes. Defects in the SCN2A gene which codes for the alpha subunit of this sodium channel are associated with benign familial infantile seizures type 3, and early infantile epileptic encephalopathy type 11.

A naturally occurring lipid pigment with histochemical characteristics similar to lipofuscin. It accumulates in various tissues in certain experimental and pathological conditions.

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