The Laboratory of Physiology of the Department of Medicine of the University of Patras led by Professor Stavros Taraviras has published a new paper in the journal EMBO Molecular Medicine on hydrocephalus, giving new hope for the treatment of hydrocephalus.
Hydrocephalus is a common neurological condition characterized by excessive circulation and accumulation of cerebrospinal fluid in the cerebral ventricles, a condition that leads to an increase in intracranial pressure. Standard treatments for the condition mainly involve neurosurgical diversion of cerebrospinal fluid, which has high morbidity and failure rates, highlighting the need for the discovery of new therapeutic approaches. The pathophysiology of hydrocephalus is highly multifactorial, but what has been shown so far is that impaired function of brain ependymal cells plays a fundamental role in hydrocephalus. Ependymal cells line the ventricles of the brain, and through moving cilia on their surface facilitate the movement of cerebrospinal fluid. Their destruction is a pathological feature of hydrocephalus.
The basic strategy is the reprogramming of cortical astrocytes and embryonic stem cells in order to regenerate ependymal cells with the perspective of improving brain enlargement and improving affected neurogenesis. To this end, and as part of this research, the Laboratory has shown that the GemC1 and McIdas genes, which are responsible for the generation of ependymal cells during embryonic development, are key regulators of multiciliated ependymal cell fate specification, and cause direct cellular reprogramming towards the ependymal cell type. Specifically, it was shown that ectopic expression of GemC1 and McIdas reprogrammed cortical astrocytes in vitro and programmed mouse embryonic stem cells into ependymal cells that were functional with multiple cilia. For McIdas was shown to be sufficient to generate functional activity in the reprogrammed astrocytes. Furthermore, McIdas expression promotes ependymal cell regeneration in two different postnatal mouse models of hydrocephalus: secondary hydrocephalus induced by intracranial hemorrhage and a genetic form of hydrocephalus and ameliorates the cytoarchitecture of the neurogenic niche.
The results of this research are encouraging, and the restoration of ependyma in animal models that mimic hydrocephalus could be exploited for future regenerative therapeutic interventions.
For the innovative research carried out in this Laboratory and for the prospect of a new cell therapy for hydrocephalus, Professor Taraviras in 2021 was awarded the prestigious international “Innovator Award Grant 2020” by the Hydrocephalus Association of the USA, the first time a Greek scientist has been awarded this prize.