Research and Development
WavoDyne Therapeutics supports both preclinical drug discovery efforts and clinical product development programs focused on neurodegenerative diseases. We have taken on the challenge of attacking neurodegenerative diseases with a fundamentally new approach. It is known that activation of the Mixed Lineage Kinase ( MLK ) class of enzymes can set off an inflammatory cascade involving the release of TNFα and IL-6, the generation of free radicals and other pro-inflammatory molecules in the CNS in response to injury, exposure to neurotoxins, or related cellular stresses; this pathologic process is referred to as neuroinflammation. Working in concert, the inflammatory cytokines and chemokines released in neuroinflammation can become autocatalytic, and overwhelm our intrinsic anti-inflammatory defense mechanisms. The process of neuroinflammation impairs the function of neurons and their synaptodendritic networks, eventually leading to impairment of cognition and memory problems.
Activation of our innate immune system in the brain creates sustained neuroinflammation. This occurs due to infiltrating macrophages and transformation of microglia into a neurotoxic phenotype. MLK-3 enzymes play a dominant role in mediating neuroinflammation; Loss of synapses and cognitive decline results.
Neuroinflammation occurs chronically in a number of different neurodegenerative diseases, the chart below is our estimate from a review of the medical literature of the approximate number of patients who suffer memory and cognitive impairments for the disease categories presented.
We’re born with > 100 billion nerve cells in our brains which do not replicate or reproduce themselves over the course of our life. These nerve cells form elaborate neural networks with other nerve cells providing us almost unlimited capacity to store memories, learn new skills, and consolidate input from our senses, etc. The touch points between nerve cells are formed by and interconnected through synapses, which serve as relay switches to transmit a neural impulse through a vast network of nerve cells. A single neuron has hundreds to thousands of synaptic connections with other nerve cells, creating a multiplexing network that allows all neurons to communicate with thousands to tens of thousands other nerve cells through the process of neural transmission. This results in an estimated 0.15 quadrillion functional contacts required in a healthy brain for full functional information transfer.
Breakdowns in neural transmission can have multiple causes, dependent on the disease state, but ultimately the nerve cell loses its capacity to self-repair in the face ongoing progressive disease pathology. Impaired functioning of a nerve cell leads to gradual losses in synaptic function, which in turn leads to ever greater progressive losses of our neural networks. Multiple failures of several synapses in a network will soon lead to loss of that network, and the death of the associated neurons. Neuroplasticity is the concept of the brain adapting or modifying its structure to requirements from the internal and external environments. This process allows us to recover from injury or compensate for neurological disorders. However, the unremitting process of neuroinflammation defeats the possible gains or improvements in cognitive function that neuroplasticity can deliver. Therefore, turning off neuroinflammation is the necessary first step to the challenge of recovering cognitive functions and memories through the compensatory process of neuroplasticity.