Neurodegenerative diseases are complex conditions, involving multiple genes and cellular pathways. They are characterised by the loss of neurons of different types (depending upon the disease) through cell apoptosis or autophagy, and the induction of destructive brain inflammation mediated by the activation of glia. In parallel, the degenerating neural tissues lose their capacity to generate fresh neurons and replace the damaged ones with activation of neural stem cells and de novo neurogenesis. Most attempts to develop therapeutics of neurodegenerative diseases target one of these deleterious conditions while the others continue their neuro-damaging actions.

Our therapeutic approach is to simultaneously target all these three phenomena (apoptosis of neurons, neuro-inflammation and neurogenesis) developing non-toxic, brain permeable, multifaceted small molecules with anti-apoptotic-neuroprotective, anti-neuroinflamnatory and neurogenic properties in one molecule.

Our key therapeutic targets are Neurotrophins and their cellular receptors. Polypeptide neurotrophins control the survival of neurons, the proliferation of neural stem cells and the formation of fresh, normal neurons, and the activation of glial cells and brain inflammation.

Using in silico molecular dynamics, artificial intelligence techniques we design and synthesise small molecules, activators of neurotrophin receptors, mimetics of endogenous neurotrophins.

Our chemists synthesize a large chemical library of our compounds, then we narrow down the number of compounds by further testing, to focus on lead compounds, precursors to our ultimate drug. We finish by optimising the lead compounds with chemistry to ensure the desired pharmacodynamic and pharmacokinetic properties. We focus on compounds that:

• specifically bind with high affinity to the appropriate for the disease neurotrophin receptor
• are efficiently and safely absorbed by the body and reach the brain
• remain in the brain long enough to act effectively
• are efficiently manufactured to produce a stable drug for clinical use
• are non-toxic with few side effects

Our researchers collaborate with world-class scientists in the field of neurodegeneration to test our lead compounds in neuronal cell cultures and tissues and in specific for the disease transgenic animal models. We thus define the exact mechanism of action of our compounds and validate their proof of concept in animals simulating the specific human neurodegenerative disease. When this work has been successful done, our scientists consider a compound testing it in humans.