For many brain diseases, including Alzheimer’s diseaseand epilepsy, there are no medicines, or existing therapiesdo not work for all patients.
Proteins that affect neurotransmitters such as dopamineand serotonin could hold the key to finding new treatments.Thanks to advances in big data and medicinal chemistry,scientists can screen thousands of molecules in the searchfor promising new drug candidates.
~” Computational chemistry offers an opportunity to lookfor untapped potential by searching for protein structuresthat might play a role in the brain, ” says Professor RonaRamsay, University of St. Andrews. “ This is the payoff fordecades of crystallography work on molecular structures.Machine learning also allows for the repurposing ofexisting drugs which have not been tested for certainneurological diseases .”
Professor Ramsay chaired COST Action CM1103, whichbrought together chemists and biologists to focus onbrain diseases where new therapies are needed. One ofthe areas she has been exploring is the potential of ” dirtydrugs ” – molecules that interact with several targets inthe brain.
“ We can now design drugs to hit specific targets. InAlzheimer’s, for example, we are developing drugsto keep acetylcholine, dopamine and serotonin in thesynapses for longer; add an anti-oxidant to preventdamage caused by dying brain cells; then add a metal to‘mop up’ oxidants which would otherwise cause problems ,”explains Professor Ramsay.
To achieve this, multidisciplinary networks have to designmolecular structures and test them in brain cells andanimal models. Participants in the network have fileda patent on one potential treatment and plan to moveforward with a view to clinical development.
Other participating groups have collaborated on atechnique which enables them to measure electricalfiring in the brain and monitor changes in the levelsof neurotransmitters – opening the door to a deeperunderstanding of the brain. The network also led to newstrategies for treating epilepsy, a novel way to assessnew compounds in animals, and an original theory on howdopamine neurotransmitters are oxidised.
The biggest value of this COST Action, according toProfessor Ramsay, arose from partnerships betweenacademics and the valuable exposure to other disciplinesthat it offered younger researchers.
This is echoed by Dr Katrina Nikolic, University ofBelgrade, Serbia, who uses computer programs todesign new compounds. “ Our collaboration with organicchemists in Spain, Germany and the UK allowed usto test compounds which could become drugs forAlzheimer’s disease ,” she said. “ This is very importantfor labs like ours and a big step forward for my career. ”
Almost half of participants were from COST InclusivenessTarget Countries, which Professor Ramsay describes as aparticularly “enriching” aspect of the network. “ I’m alsovery proud that 50% of our network was female at theoutset – not many Actions in chemistry can say that! ”
The network is currently finalising an e-book of itsresearch results and many of its members continueto collaborate. Members in Spain, the UK and Germanyare developing a three-in-one compound that can targetthree brain receptors linked to Alzheimer’s diseasein a single drug. Members from Italy and Turkey arerunning an EU-funded project training 12 PhD students inneuroscience research, focusing on neurodegeneration,neurotherapeutics development and neurorepair. Eachstudent also receives 3-5 months training on cutting-edgetechnology within a company from the industry.