Clinical Trial For Rett Syndrome Launched
“Pharmacological Treatment of Rett Syndrome with Glatiramer Acetate (Copaxone)”.
Aleksandra Djukic M.D. PhD, Associate professor of Neurology and Pediatrics, Director, Tri State Rett Syndrome Center, The Saul R. Korey Department of Neurology
Researchers at the Rett Center at Montefiore have begun a phase 2 open label trial to test a potential drug treatment for Rett syndrome, the leading known genetic cause of severe neurological impairment in girls. The drug, Copaxone (generic name - Glatiramer acetate) is medication FDA approved for the treatment of multiple sclerosis. Copaxone’s high safety profile has been documented in large cohorts of patients for more than 12 years.
The trial, now enrolling patients, marks the beginning of a trend toward drug treatments seeking to modify the underlying mechanisms of neurological dysfunction in Rett syndrome, rather than just treat symptoms such as seizure, sleep disruption or anxiety. Research published in 2007 demonstrated that severe symptoms in animal models of Rett syndrome can be reversed, even in advanced stages of disease.
Background/rationale for the study:
In Rett syndrome brain cells aren't actually lost, instead poor maturation of connections between brain cells (synapses) prevents effective neurological functioning, and is the main morphological feature of the disease. The MeCP2 gene plays a major role in transcriptional regulation of other genes, one of which is the gene encoding brain-derived neurotrophic factor (BDNF).
The disease progression and severity of symptoms is directly affected by the level of BDNF expression. An increase of BDNF levels (by genetic manipulations or pharmacological agents) leads to delayed onset of Rett syndrome-like symptoms in experimental models; rescued gait/mobility, improved quality of life and increased survival rates.
Copaxone treatment by subcutaneous injection caused elevation of BDNF levels. Quantitative immunofluorescence assays showed about a twofold increase in neuronal expression of BDNF following Copaxone treatment.
We expect that an increase in BDNF levels with Copaxone administration will stimulate communication between brain cells (synaptic maturation), which will lead to amelioration of symptoms (motor functions/gait, cognitive functions, breathing, encephalopathy and improve quality of life) for girls with Rett syndrome.
The 6 month pilot study will include girls with genetically confirmed Rett syndrome, who are 10 years or older and ambulatory.
Exclusion criteria: Prolonged Qtc (obtained within 30 days prior to enrollment); Presence of co morbid non-Rett related disease; Presence of immunodeficiency requiring IVIG 3 months prior to enrollment; Allergy/sensitivity to GA or mannitol.
The clinical trial is funded by the Rett Syndrome Research Trust.