The central nervous system (CNS) is protected from harmful and neurotoxic components by strict barriers between the blood and the nervous tissue. This neuroprotective barrier is formed by specialized endothelial cells that line the lumen of the blood vessels in the CNS tissue. Its function is closely controlled through continuous interactions with surrounding cells such as pericytes, astrocytes and neurons.
It is becoming clear that the vascular endothelium of the CNS is more than just a barrier; it is an active and plastic system which selectively takes up nutrients, secretes neurotrophic and neuromodulatory factors while excluding compounds that are harmful to the CNS. The different endothelial functions are schematically represented in the figure on the right. Increasing evidence shows that failure of any or all of these functions plays a central role in many neurodegenerative disease
“…Recent studies have shown numerous additional roles of these barriers, including an involvement in neurodevelopment, in the control of cerebral blood flow, and — when barrier integrity is impaired — in the pathology of many common CNS disorders such as Alzheimer’s disease, Parkinson’s disease and stroke…” Neuwelt et al. Nature Reviews Neuroscience 12, 169-182 (March 2011)
Chronic dysfunction of the blood-CNS-barrier is a key event in a number of neurological disorders, such as multiple sclerosis (MS), various forms of dementia, after a trauma or stroke and in amyotrophic lateral sclerosis (ALS). As a consequence, neurotoxic blood components can enter the CNS, while the supply of oxygen, glucose and neurotropic factors as well as the efflux of waste products is strongly impaired. We believe that these phenomena largely contribute to the pathogenesis of neurodegenerative diseases
Brendinn Therapeutics’ aim: Restore brain endothelial function to limit progression of neurological disorders.
In our proof of concept studies, we provide evidence for this rationale using MS based models.