Neuroscience Drug Discovery and Cell Therapy

The human brain is the primary organ of the central nervous system and controls most of the activities of the body by making critical homeostasis decisions based on a series of complex input information received from various organs. 

There are over 500 debilitating diseases and disorders of the central nervous system (CNS) and many are among the most severe in terms of individual fatalities and cognitive impairment that affects societal well-being. 

Although, the CNS is of central importance to human health, therapeutic approaches to many CNS diseases and disorders are especially difficult due to the complexity of the brain and the delivery of molecules past the blood brain barrier. 

The human brain is supplied with blood by specialized vasculature that is structurally and functionally distinct from that of the periphery. A defining feature of this vasculature is a physical blood-brain barrier (BBB). 

The BBB separates blood components from the brain microenvironment, regulating the entry and exit of ions, nutrients, macromolecules, and energy metabolites. Over the last two decades, physiological studies of cerebral blood flow dynamics have demonstrated that substantial intercellular communication occurs between cells of the vasculature and the neurons and glia that surround the vasculature. These findings suggest that the BBB does not function independently, but as a module within the greater context of a multicellular neurovascular unit (NVU) that includes layers of endothelial cells, astrocytes, pericytes, and neurons as well as the blood vessels themselves. 

The multiple cell type components of the NVU act in concert to modify cerebrovascular function and permeability in health and disease. 

CNS Drug Delivery Limitations

The most severe obstacle to the delivery of drugs into the brain is the presence of the blood− brain barrier/Neurovascular unit (NVU). The NVU limits the traffic of substances between the blood and the brain tissue and is made of a series of oriented layers of interconnected cell types that intricately regulate the passage into and out of the neurovascular tissue. 

From a therapeutic view, a significant number of potential drugs fail because of the poor penetration through the NVU. Most studies are slow and expensive and require the use of mouse models where drugs are given, the animal then sacrificed and the brain analyzed. The mouse brain is notorious as a poor human brain model as the behaviour of the cells and the receptor distribution in the BBB/NVU is very different than human. Therefore, it is of crucial importance to test the NVU permeability of a drug candidate as early as possible in the drug developmental pipeline. 

In order to meet this need realistic in vitro models of the NVU are desperately required to advance CNS therapeutics. This is a major obstacle as you require at least 4 different cell types oriented in layers to form a NVU tissue in vitro. Current technology uses rudimentary monolayers of cells or transwell assays to model the blood brain barrier that does not allow for the formation of a 3D layered NVU tissue with the cells connected to each other in the correct format. 

OrganoLinX Therapeutics has pioneered  a molecular approach that can rapidly assemble neuronal cells in layers to form an integrated 3D blood brain barrier / neurovascular unit for true drug discovery and disease modeling.   The 3D brain tissue is being used to discover novel drug molecules for Epilepsy, Parkinson's Disease and Ischemic Stroke.  By introducing diseased neuronal cells into the 3D brain tissue assembly process, the cell biology of various neurological diseases can be accurately studied.  

A promising new approach to treat neurological diseases is the implantation of new neuronal cells directly to specific regions of the brain.   Several diseases including, Epilepsy, Parkinson's and Ischemic Stroke result in the loss or irrevocable damage of neuronal cells.     

OrganoLinX is using a novel approach to generate 3D human brain organoids with the correct cell types and interactions to implant into patients with severe Neurological trauma or disease.  

OrganoLinX has the only technology that is able to assemble multiple different neuronal cell types in the correct ratio and size to generate reproducible brain organoids for study and implantation. 

OrganoLinX has developed a proprietary technology that is able to assemble any cells together to form layer by layer tissues or complex organoids.   

ViaGlue uses a combination of bio-orthogonal chemistry and cell surface engineering to rapidly install molecules on cell surfaces for subsequent cell assembly.   

ViaGlue has been shown to be non-toxic, safe and able to assemble many different cell types.   ViaGlue is a scaffold free method that does not use polymers or hydrogels.   

Using ViaGlue, the resulting tissue or organoid is entirely made of cells.   OrganoLinX has a separate Life Science Reagents division that sells ViaGlue and a wide range of other reagents and bioconjugation molecules.  Please visit   www.OrganoLinX.com to learn more.