# The promise of molecular science in brain health. What breakthroughs are anticipated in the next 20 years?

## TL;DR

The paper reviews past and future molecular science breakthroughs in brain health, focusing on advances in therapies and biomarkers, and predicting future progress in gene editing and new drug development.

## Contribution

The paper provides a forward-looking interdisciplinary analysis of molecular science's role in brain health, identifying key future research directions.

## Key findings

- Molecular science has advanced brain health through therapeutic antibodies and RNA-targeted drugs.
- Future progress is expected in gene editing, RNA interventions, and novel drug development.
- Improved biomarkers and understanding of brain structure-disease relations are critical needs.

## Abstract

•In the past twenty years molecular science has delivered progress in therapeutic antibodies, biochemical markers, gene therapy and drug re-purposing.•Areas of need relevant to brain health include: brain development and plasticity of neuronal circuits; more refined molecular biomarkers for diagnosis and as clinical trial endpoints; better understanding of the relation of brain structure to cognitive disease.•The next twenty years is likely to witness progress in: gene editing and RNA targeted interventions; manipulating cell fate; brain-immune interactions; new classes of drugs, derived from novel chemistry.

In the past twenty years molecular science has delivered progress in therapeutic antibodies, biochemical markers, gene therapy and drug re-purposing.

Areas of need relevant to brain health include: brain development and plasticity of neuronal circuits; more refined molecular biomarkers for diagnosis and as clinical trial endpoints; better understanding of the relation of brain structure to cognitive disease.

The next twenty years is likely to witness progress in: gene editing and RNA targeted interventions; manipulating cell fate; brain-immune interactions; new classes of drugs, derived from novel chemistry.

Brain health means optimal physiological brain function across the normal life-course. It encompasses not only healthy brain aging but also brain diseases, their diagnosis and treatment. In all these areas, molecular science has advanced our understanding.

This multi-disciplinary review combines viewpoints from laboratory science, clinical medicine and the bioscience industry. First, we review the advances that molecular science has brought to brain health in the past twenty years. These include therapeutic antibodies for CNS diseases (multiple sclerosis, Alzheimer disease) and the dramatic introduction of RNA-targeted therapeutics. Second, we highlight areas where greater molecular understanding is needed. Salient examples are the relation of brain structure to cognitive symptoms, and molecular biomarkers for diagnosis, target discovery and testing of interventions. Finally, we speculate on aspects of molecular science that are likely to advance brain health in the next twenty years. These include: cell senescence and chronobiology; gene editing (notably, CRISPR) and RNA targeting (RNA interference, miRNA manipulation); brain-immune interactions; novel drug targets (AQP4, HIF1, Toll-like receptors); and novel chemistry to make new drugs (molecular machines, quantum molecular modelling and “click” chemistry). Early testing of the relationships between molecular pathways and clinical manifestations will drive much-needed breakthroughs in neurology and psychiatry.