Wednesday, June 19 2019

In the last decades, enormous effort was put into understanding how the brain is organized and functions, with much of this progress based on animal models. Nevertheless, a lot remains unknown, including the causes and mechanisms underlying the debilitating brain pathologies that are expected to affect large parts of the population at different times throughout their lives. For example, neurodevelopmental disorders (e.g., autism-spectrum disorders, Rett syndrome, Down syndrome) are severe and chronic psychiatric/neurological conditions with early onset that affect only a small fraction of the population. Conversely, neurodegenerative diseases and stroke have increased incidence with aging and are thus expected to grow rapidly in frequency owing to the demographic change.
Although displaying very different etiology, most brain disorders present a strong genetic component and share features, such as cognitive impairment, and often some comorbidity (e.g., increased seizure susceptibility, sleep disorders, vision impairment). In general, treatment options for brain disorders are severely limited and mostly address comorbidity rather than the core symptoms and/or the causes of the disease. This is due to several reasons:

  • Conclusions drawn from animal models translated poorly to patients.
  • Most of the research on brain disorders in recent years focused on seeking convergent pathways that account for the large diversity of genetic variations in diseased persons.
  • Although genomic technologies have identified hundreds of mutations associated with increased risk, the understanding of the underlying mechanisms is still limited and requires much deeper investigation.

These issues highlight the importance of continuing basic research in neuroscience, and in particular, the development of patient-derived models that could improve the translation of conclusions drawn from model systems to patients.

In this respect, a neuroscience program that tries to parallel animal data with data derived from human cells is desirable. In this regard, FPS focuses on the development of human-derived iPS cells and organoid models, in order to better focus research on the mechanisms underlying carefully-defined cases, and ultimately to test tailored therapeutic approaches.