EuroNeurotrophin · A European training network for the discovery of neurotrophins small molecule mimetics as candidate therapeutic agents for neurodegeneration and neuroinflammation

A European training network for the discovery of neurotrophins small molecule mimetics as candidate therapeutic agents for neurodegeneration and neuroinflammation

Neurodegenerative diseases (ND) like Alzheimer’s Disease (AD), Parkinson’s Disease (PD) Multiple Sclerosis (MS) and Neurone Disease (MND) are on the rise in developed societies worldwide. Just AD affects 36 million people worldwide and 7 million in Europe. The economic burden for ND exceeds 724 billion € and it will become a trillion euros by 2020. Currently, there exists no cure for any ND, and most of the available drugs fail to tackle ND pathogenesis. Neurotrophins are a family of closely related secreted proteins that have been shown to control a number of aspects of survival, development and function of neurons both in the central and the peripheral nervous systems. Preclinical studies point to the therapeutic potential of neurotrophins in preventing or slowing the progression of ND. Thus, neurotrophins have been proposed as therapeutic agents for neurodegenerative diseases. However, the poor pharmacokinetic properties of neurotrophins, mainly because of their sensitivity to proteolysis, restricted penetration of the blood–brain barrier, and limited ability to diffuse in tissues, render their use as drugs prohibitive. A potential approach for addressing neurotrophin limitations is the development of synthetic, small molecule, neurotrophin mimetics with favourable profiles of stability, tissue penetration and targeted biological actions. EuroNeurotrophin is the first European consortium to study small molecule neurotrophin mimetics (synthetic or natural) in depth, use them as molecular probes to interrogate neurotrophins, and emphasise their clinical translation. The consortium builds on previous successful collaborations, enriched with key specialists and partners. The consortium consists of 12 leading European research groups and 5 private companies of complementary expertise covering all steps of drug discovery and development. Jointly, it aims to accelerate the translation of identified lead compounds to drug candidate molecules through the collaborative training of 14 early-stage researchers. The EuroNeurotrophin objectives were to: 1. Develop small molecule mimetics of neurotrophins capitalising on a synergistic combination of medicinal chemistry, isolation of natural products, computer-aided drug design, structural biology, molecular biology, pharmacology high throughput screening (HTS) and ‘omics’ technologies. 2.. Educate 14 young researchers regarding the knowledge underpinning the neurotrophin related field and on drug and natural products research for neurodegenerative diseases. 3. Provide to 14 ESRs a multidisciplinary research and industrial training, as well as training in a comprehensive set of transferable skills. 4. Create a new generation of young scientists with a broad understanding and skill set in chemical biology with emphasis on the neuroscience field.

Data: CORDIS, © European Union