Transcranial Photobiomodulation in Rett Syndrome: A Mechanistic Review and Therapeutic Hypothesis

Area of Science:

• Neuroscience
• Genetics
• Biomedical Engineering

Background:

• Rett syndrome (RTT) is a severe X-linked neurodevelopmental disorder primarily caused by MECP2 gene variants.
• Current therapeutic options for RTT are limited, highlighting the need for novel disease-modifying treatments.

Purpose of the Study:

• To propose a mechanistic framework for using transcranial photobiomodulation (tPBM) as an adjunctive therapy for Rett syndrome.
• To explore the potential of tPBM in addressing the core pathophysiological mechanisms of RTT.

Main Methods:

• Review of key cellular mechanisms implicated in RTT pathogenesis, including mitochondrial dysfunction, oxidative stress, neuroinflammation, and impaired synaptic plasticity.
• Summary of the known bioenergetic, redox, anti-inflammatory, and neurotrophic effects of tPBM.

Main Results:

• A convergence was identified between the cellular pathways affected in RTT and the known actions of tPBM.
• tPBM demonstrates potential to ameliorate bioenergetic deficits and signaling pathway abnormalities characteristic of RTT.

Conclusions:

• The mechanistic overlap suggests tPBM could serve as a multi-target neuromodulation strategy for RTT.
• Preclinical studies in Mecp2-deficient models and early-phase clinical trials of tPBM in RTT patients are warranted.