Therapeutic Potential of Transcranial Focused Ultrasound for Rett Syndrome

Abstract

Rett syndrome (RTT) is a severe neurodevelopmental disorder occurring almost exclusively in females and is caused by loss-of-function mutations in the gene encoding methyl-CpG-binding protein 2 (MeCP2) in the majority of cases. MeCP2 is essential for the normal function of nerve cells, including neuronal development, maturation, and synaptic activity. RTT is characterized by normal early development followed by autistic-like features, slowed brain and head growth, gait abnormalities, seizures, breathing irregularities, and cognitive disabilities. Medical management in RTT remains supportive and symptomatic. Brain-derived neurotrophic factor (BDNF) has been implicated in the pathophysiology of RTT. Recent studies have shown a phenotypic reversal by increasing BDNF expression in a RTT mouse model. Thus, manipulation of BDNF expression/signaling in the brain could be therapeutic for this disease. Transcranial focused ultrasound for (tFUS) can noninvasively focally modulate human cortical function, stimulate neurogenesis, and increase BDNF in animal studies. Consequently, tFUS may be of therapeutic potential for Rett syndrome. Further evaluation of the therapeutic effects of tFUS in Mecp2 deficient animal models is needed before clinical trials can begin.

Acoustically Targeted Noninvasive Gene Therapy in Large Brain Regions

“…Although FUS is a technique for targeting specific brain regions with high precision, FUS-BBBO can also be useful in the treatment of disorders affecting large swathes of the brain such as hereditary genetic disorders like Stxbp1 encephalopathy, Huntington’s Disease, or Rett disease 1,5,47 . Additionally, brain regions in nonhuman primates and humans are often larger than the size of the ultrasound beam.…”