RNA-based therapies for neurodevelopmental disorders: innovative tools for molecular correction

Area of Science:

• Neuroscience
• Genetics
• Molecular Biology

Background:

• Neurodevelopmental disorders (NDDs) often stem from specific genetic mutations.
• Current treatment options for many NDDs are limited, especially for syndromic forms.
• Restoring normal RNA and protein expression is a key therapeutic strategy.

Purpose of the Study:

• To review advances in RNA-based therapeutics for NDDs.
• To highlight the potential of various RNA molecules in treating genetic disorders.
• To explore the application of RNA medicine in intellectual disability, autism spectrum disorder, and developmental epileptic encephalopathy.

Main Methods:

• Review of diverse RNA-based therapeutic classes: antisense oligonucleotides (ASOs), antagoNATs, SINEUPs, RNAi, ExSpeU1s, and saRNA.
• Analysis of therapeutic applications targeting specific genetic mutations in NDDs.
• Examination of RNA molecule efficacy in preclinical and clinical investigations.

Main Results:

• RNA-based therapeutics show promise for syndromic ID (Fragile X, MECP2 duplication, FOXG1, Angelman syndrome).
• Investigational RNA approaches are being explored for ASD-related conditions (e.g., CHD8 mutations).
• RNA molecules are being developed to address severe, pharmaco-resistant epilepsy in DEEs by targeting genes like CDKL5, SCN1A, and others.

Conclusions:

• RNA technologies provide specific and flexible gene-targeted interventions for NDDs.
• The field of RNA medicine is rapidly expanding, offering new hope for molecular correction.
• This review serves as a resource for researchers and clinicians on innovative RNA tools for NDDs.