33076
Novel Therapeutic Modalities for Neurodevelopmental Disorders
The biology of neurodevelopmental disorders and ASD has benefited from the identification of genetic and molecular pathologies, particular in rare syndromic and monogenetic disorders. Drug discovery for ASD and neurodevelopmental disorders has however been constrained by limitations in the ability to adequately pharmacologically-modify genetic targets through traditional small molecule and protein engineering approaches.
Objectives
To describe novel therapeutic modalities to directly modulate RNA and DNA-based targets in neurological disorders and identify how they may be deployed in ASD and critical success factors in translating such therapies to the clinic.
Methods
We will review recent experience with gene modulation and RNA therapies with a particular focus on targeting the central nervous system, the promise and limitations of genomic medicine in ASD as well as emerging technologies that can be applied to drug discovery and development in ASD.
Results
Genomic medicine for CNS disorders are a reality and have the potential to greatly expand the drug discovery toolbox and target space in ASD. Experience with the current generation of DNA and RNA-modulating therapies also highlight areas of uncertainty and opportunity in development of next-generation technologies as well as important factors in drug candidate selection prior to entry into humans. We primarily review vector-based, oligonucleotide and small molecule approaches.
Conclusions
Advances in drug technologies are poised to have a significant impact to modulate genetically-defined targets in people with ASD. These will begin to provide answers to the salience of these targets in the neurobiology and pathophysiology of these conditions as well as a new generation of investigational therapies for ASD and associated disorders.