RTT requires a multidisciplinary approach. Genetic testing results are essential for enrolment in clinical trials. Therapeutic strategies are as follows:
• Seizures need to be treated with antiseizure treatment. Antiseizure treatment efficacy is age-dependent and valproate is recommended under 5 years of age, while carbamazepine is the drug of choice for patients over 15 years. Lamotrigine may be also preferred. Levetiracetam is also a choice but should be considered carefully because of potential mood symptoms and agitation. Benzodiazepines such as clobazam and cannabidiol can be chosen in refractory cases.
• Molecular targets: Brain-Derived Neurotrophic Factor (BDNF) which is down-regulated by loss of MeCP2 is a molecular target through neuro-transmitter and growth factor metabolism. While animal studies showed positive results, these were not confirmed among humans. A known synthetic anolog of glycine-proline glutamate, the N-terminal tripeptide of the insulin like growth factor 1 protein which is called Trofenetide and ketamine are promising candidates.
• Gene theraphy: Adenoassociated virus (AAV) mediated gene theraphy was tolerable in first patients and is a promising treatment method including other gene therapies as genome editing, RNA editing and X-chromosome reactivation.
• Future theraphies: Nanoparticle-based delivery systems with lesser immunogenicity and higher genetic payload capacity than classical viral vectors are promising future theraphies.
• Treatment of endocrine disorders: dietary theraphies against weight loss and malnutrition, gonadal function theraphies against precocious puberty and menstrual irregularities, thyroid hormone replacement for hypothyroidism are main treatment strategies.
• Orthopedic approach: Regarding the basic problem in RTT is osteoblastic dysfunction causing decreased bone formation, theraphies against bone resorption will not work properly. Calcium, protein and phosphate containing dietary regulation is necessary.
MECP2