GENE TARGET: A framework for evaluating Mendelian neurodevelopmental disorders for gene therapy

Area of Science:

• Neuroscience
• Genetics
• Therapeutics

Background:

• Gene therapy interest for neurodevelopmental disorders is rising due to genetic discoveries and technological advances.
• Current therapy development prioritization is fragmented, driven by competing stakeholder interests.
• A systematic framework is needed for rational and efficient gene therapy development.

Purpose of the Study:

• To outline key features for evaluating Mendelian neurodevelopmental disorders for gene therapy suitability.
• To propose a mnemonic, GENE TARGET, and a scoring rubric for a standardized assessment.
• To identify translational pipeline gaps and inform research prioritization.

Main Methods:

• Defined features across four domains: genetics, preclinical validation, clinical considerations, and ethics.
• Developed a preliminary scoring rubric to quantify suitability for gene therapy.
• Proposed the GENE TARGET mnemonic for feature recall.

Main Results:

• The GENE TARGET framework provides a systematic method to evaluate and compare disorders for gene therapy potential.
• A composite GENE TARGET suitability (GTS) score can be derived for each disorder.
• The framework aids in identifying specific gaps in the translational research pipeline.

Conclusions:

• The proposed GENE TARGET framework offers a consolidated and rational approach to prioritizing neurodevelopmental disorders for gene therapy development.
• Systematic evaluation can optimize resource allocation and accelerate therapeutic progress.
• This framework supports informed decision-making in gene therapy research and development.