Study of the Pathogenesis of Rett Syndrome
OBJECTIVES: I. Extend current knowledge of the phenotype and natural history of Rett syndrome (RS).
II. Continue the search for a cytogenetic and/or DNA marker. III. Study the effects of cholinergic drugs based on preliminary evidence for reduced levels of brain acetylcholine, while continuing supportive care to modify seizures, respiratory abnormalities, and motor disturbances, and improve nutrition, behavior, and learning.
IV. Identify targets for future therapeutic interventions, e.g., growth factors, to influence neurologic recovery.
PROTOCOL OUTLINE: Patients receive a comprehensive clinical evaluation including an ophthalmologic exam; speech, communication, and developmental assessment; nutritional evaluation; neurologic exam; respiratory monitoring; and cytogenetic studies.
Selected patients with malnutrition are given night feedings of Pediasure with Fiber by nasogastric tube. Specific recommendations for feeding techniques and diet are made.
Selected patients with seizures or severe hyperventilation and progressive rigidity are nonrandomly assigned to dextromethorphan or topiramate therapy.
Oral dextromethorphan is maintained 6 months to 1 year; duration of therapy depends on response. Oral topiramate is given for 6 months to 1 year, and Aricept for 6 months to 1 year.
Concurrent anticonvulsants may require dose adjustments while on above protocols. Supportive care for constipation, scoliosis, and weight loss is allowed.
Primary Purpose: Treatment
dextromethorphan, topiramate, Donepezil
Office of Rare Diseases (ORD)
Results (where available)
- Source: http://clinicaltrials.gov/show/NCT00004807
- Information obtained from ClinicalTrials.gov on July 15, 2010
Medical and Biotech [MESH] Definitions
Methyl-cpg-binding Protein 2
A DNA-binding protein that interacts with methylated CPG ISLANDS. It plays a role in repressing GENETIC TRANSCRIPTION and is frequently mutated in RETT SYNDROME.
An inherited neurological developmental disorder that is associated with X-LINKED INHERITANCE and may be lethal in utero to hemizygous males. The affected female is normal until the age of 6-25 months when progressive loss of voluntary control of hand movements and communication skills; ATAXIA; SEIZURES; autistic behavior; intermittent HYPERVENTILATION; and HYPERAMMONEMIA appear. (From Menkes, Textbook of Child Neurology, 5th ed, p199)
Dextro form of levorphanol. It acts as a noncompetitive NMDA receptor antagonist, among other effects, and has been proposed as a neuroprotective agent. It is also a metabolite of DEXTROMETHORPHAN.
22q11 Deletion Syndrome
Condition with a variable constellation of phenotypes due to deletion polymorphisms at chromosome location 22q11. It encompasses several syndromes with overlapping abnormalities including the DIGEORGE SYNDROME, VELOCARDIOFACIAL SYNDROME, and CONOTRUNCAL AMOMALY FACE SYNDROME. In addition, variable developmental problems and schizoid features are also associated with this syndrome. (From BMC Med Genet. 2009 Feb 25;10:16) Not all deletions at 22q11 result in the 22q11deletion syndrome.
Methyl analog of DEXTRORPHAN that shows high affinity binding to several regions of the brain, including the medullary cough center. This compound is an NMDA receptor antagonist (RECEPTORS, N-METHYL-D-ASPARTATE) and acts as a non-competitive channel blocker. It is one of the widely used ANTITUSSIVES, and is also used to study the involvement of glutamate receptors in neurotoxicity.
Rett syndrome (RTT) is a disorder in which the nervous system does not develop properly. RTT generally affects girls, but there are some boys who have been diagnosed with RTT. Symptoms of...
Increased brain glutamate and its NMDA receptors found in the brain of younger Rett syndrome (RTT) patients cause toxic damage to neurons (the brain's nerve cells), and contributing to EEG...
The purpose of this study is to evaluate and determinate the functional abilities in Rett syndrome conforming to the established Pediatric Evaluation of Disability Inventory (PEDI).
Rett Syndrome (RTT) is a genetic brain disorder that occurs almost exclusively in females and is usually caused by a change (mutation) in the gene MECP2. The disorder is characterized by m...
Previous studies using topiramate in Tourette subjects have shown that with the use of this medication subjects report that their tics get better. The purpose of this study is to study if...
Rett syndrome is a severe neurodevelopmental disease with a prevalence of 0.88 per 10,000 girls aged 5-18 years, and is often caused by mutations in methyl-cytosine-phosphate-guanine (CpG)-binding pro...
This study utilised developmental profiling to examine symptom presentation in 14 girls with genetically confirmed Rett Syndrome and whose family was participating in the Australian Rett Syndrome or I...
Epilepsy often occurs in Rett syndrome and is considered a major problem. The aim of this study was to define the clinical features of epilepsy and the correlation between seizures and both genotype a...
Dextromethorphan, an antitussive drug, has a neuroprotective property as evidenced by its inhibition of microglial production of pro-inflammatory cytokines and reactive oxygen species. The microglial...
To the Editor: In the Donepezil and Memantine in Moderate to Severe Alzheimer's Disease (DOMINO) study, Howard and coauthors (March 8 issue)(1) found that the magnitude of benefit, as assessed with th...