Gene-Tailored Treatments for Brain Disorders: Challenges and Opportunities

Abstract

Brain disorders pose major challenges to medicine and treatment innovation. This is because their spectrum spans inflammatory, degenerative, traumatic/ischaemic, and neoplastic disease processes with a complex and often ill- understood aetiology. An improved genetic and genomic understanding of specific disease pathways offers new approaches to these challenges, but at present it is in its infancy. Here, we review different aspects of the challenges facing neuromedicine, give examples of where there are advances, and highlight challenges to be overcome. We see that some disorders such as Huntington's disease are the product of single gene mutations, whose discovery has been leading to the development of new targeted interventions. In the field of neurosurgery, the identification of a number of mutations allows an elaborated genetic analysis of brain tumours and opens the door to individualised therapies. Psychiatric disorders remain the area where progress is slow. Genetic analyses show that for major common disorders such as schizophrenia and depression there are no single gene alterations which offer options for targeted therapy development. However, new approaches are being developed to leverage genetic information to predict patients' responses to treatment. These recent developments hold promise for early diagnosis, follow-up with personalised treatments with adjusted therapeutic doses, predictable responses, reduced adverse drug reactions, and personal health planning. The scenario is promising but calls for increased support for curiosity-driven research into the mechanisms of normal brain functioning as well as challenging adaptations of health care and research infrastructures, encompassing legal frameworks for analysing large amounts of personal data, a flexible regulatory framework for correlating big data analyses in cooperative networks between academia and the drug development industry, and finally new strategies for brain banking in order to increase access to brain tissue samples. To make personalised medicine for brain disorders a reality, a joint effort between all relevant stakeholders - among which patients and patient organisations should play an important role - is required.

Genetic Signatures of Drug Response Variability inDrosophila melanogaster

“…However, clinical application of personalized medicine is still in its infancy and only rarely are genetic profiles considered in the treatment plan. Thus, basic research is needed before such strategies can be implemented in the clinic (De Grandis and Halgunset 2016; Esposito et al 2016). A particular unresolved issue is the lack of knowledge of the molecular genetic mechanisms that form the variability in responses to medical treatments.…”