OBJECTIVES : Rett syndrome is a rare non-inherited genetic postnatal neurological disorder that occurs almost exclusively in girls and leads to severe developmental impairment. First symptoms appear at 6 to 18 months. Rett Syndrome is caused by a mutation in the MECP2 gene on the X chromosome. This review aimed to identify and assess clinical trials on therapeutic approaches in people with Rett syndrome.

METHODS : A systematic literature review was performed in Medline, Embase, ClinicalTrials.gov registry, Cochrane databases on 25^th June 2018. A total of 652 articles were identified, out of which 28 publications (19 studies) were included in the qualitative synthesis. Data on the efficacy and safety of treatments for Rett syndrome were extracted.

RESULTS : Out of 19 studies including from 8 to 73 patients identified, 18 focused on pharmacological treatments of Rett syndrome symptoms. We did not identify studies targeting the cause of the disease. Overall, 14 (74%) were RCTs, 5 (26%) were single-arm studies, and 18 studies reported follow-up duration of 1 to 26 months. The most commonly investigated primary endpoints were: Rett Syndrome Gross Motor Scale (RSGMS), Clinical Severity Score (CSS), Motor and Behavioral Assessment (MBA), the Anxiety Depression and Mood Scale (ADAMS). A significant clinical benefit was demonstrated for naltrexone (RSBQ), trofinetide (RSQB, CGI-GI and VAS), and mecasermin (ADAMS depressed Mood) in comparison to placebo. Most treatments showed a lack of significant improvement. The availability of recent clinical practice guidelines and treatment patterns data was limited.

CONCLUSIONS : There is a lack of effective therapies in Rett syndrome; available treatment options are focused on symptoms without an impact on the disease progression. There is a great demand for the development of safe and effective causative treatments such as gene therapy which could improve quality of life and prognosis of patients with Rett syndrome.