Pharmacological Treatment of Rett Syndrome With Glatiramer Acetate (Copaxone)

Montefiore Medicine Academic Health System

Status and phase: Completed; Phase 2

Conditions: Rett Syndrome

Treatments: Drug: Glatiramer Acetate

Study type: Interventional

Funder types: Other

Identifiers

NCT02153723

13-05-117

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 10 patients

Sex: Female

Ages: 10+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Female patients with genetically confirmed Rett Syndrome (RTT)
• Age: 10 or more years old. Selection of the age is based on the available evidence of the safety of Glatiramer Acetate (GA) in this group, and the relative homogeneity/stability of the phenotype, which is not expected to spontaneously change within a 6 month period at this age
• Ambulatory (with our without support)

Exclusion criteria

• Prolonged Qtc (obtained within 30 days prior to enrollment)
• Presence of co morbid non-Rett related disease
• Presence of immunodeficiency requiring intravenous immunoglobulin 3 (IVIG 3) months prior to enrollment
• Allergy/sensitivity to GA or mannitol
• Inability or unwillingness of legal guardians to give written informed consent

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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10 participants in 1 patient group

Copaxone

Experimental group

Description:

Dose escalation: Study drug will be administered once a week for 4 weeks, twice a week for 4 weeks and daily for 24 weeks. Drug is administered as a subcutaneous injection.

Treatment:

Drug: Glatiramer Acetate