Hot on the heels of brain diseases with the Neurodegenerative Disease Initiative (NDI)
This week, London played host to the opening symposium of The Wellcome Trust/MRC Neurodegenerative Disease Initiative (NDI), a collaboration of UK neuroscientists from University College London (UCL), King’s College London (KCL), and Cambridge University. Joseph Jebelli, a PhD candidate at the UCL Institute of Neurology, reflects on the event.
Neurodegenerative diseases are placing an ever-increasing burden on our society, and an even greater strain on the individuals and families who are directly affected by them. It is vital that we, both scientists and public, improve our understanding of these diseases. The aim of the Degenerating Brains event was to bring the public up to speed on current research into brain disorders such as Alzheimer’s, Huntington’s, and motor neuron disease. Members of the public (including patients themselves), clinicians, and students, listened with rapt attention as leading scientists spoke on the progress that has been made, and the challenges that lie ahead.
Professor John Hardy, a geneticist and Alzheimer’s researcher at UCL, began by discussing how advances in DNA sequencing technology are unmasking evermore disease-associated genes. This work was made possible by the completion of the human genome project in 2003, and the advent of genome-wide association studies (GWAS) in 2006.
‘We are in a golden age of genetics’, said Prof. Hardy. ‘Perhaps the whole genetic architecture of Alzheimer’s disease will be sorted out in the next three or four years, but the real question is when that genetic knowledge is going to be translated into treatments, and that’s difficult to predict’.
Genetics is now advancing exponentially, and sequencing a single person – which once took 15 years and cost over £200 million – now takes just five days and costs £5000. As a result, the genomes of thousands of Alzheimer’s patients are being sequenced in the hunt for genetic clues to what causes the condition.
As nearly all research is currently based on genetic findings, it is hoped this information will unveil the biological architecture of Alzheimer’s disease, which in turn will offer cell biologists and pharmaceutical companies novel therapeutic drug targets. Indeed, many scientists believe this will lead to the advent of personalised medicine, which is tailored to target the unique pathology of different individuals suffering dementia.
Professor Christopher Shaw, a neurologist and scientist at KCL, gave an enthralling talk on the cell biology of amyotrophic lateral sclerosis (ALS), the main form of motor neuron disease. ALS is a devastating disease that progressively destroys motor neurons – specialised nerve cells that control movement – leading to muscle weakness and paralysis. There is currently no cure for the disease, and sadly most people with ALS die within 3-5 years of the diagnosis.
In 2008, Professor Shaw’s research group found genetic mutations in proteins thought to be responsible for 95% of all ALS cases. These proteins – called TDP-43 and FUS – form sticky clumps inside motor neurons, which are poisonous to the cells, and eventually kill them. How and why this happens, however, remains unclear.
‘Neurons have a great deal of difficulty clearing proteins generally’, Prof. Shaw told me. ‘Neurons are in a very protected environment, and they don’t like a lot of dramatic change. Other cells can just die and be replaced, but that’s not an option for nerve cells’.
ALS researchers around the world are now galvanised into studying TDP-43 and FUS abnormalities in a variety of experimental models, including flies, mice, and zebrafish. What’s more, Prof. Shaw and his colleagues recently published groundbreaking work using adult human stem cells to show the direct effects of abnormal TDP-43 on human motor nerves – published in the journal Proceedings of the National Academy of Science (PNAS).
Finally, Professor David Rubinsztein, a molecular geneticist at Cambridge University, gave a thought-provoking talk on ‘autophagy’. This is a kind of waste-management system in cells that has evolved to degrade and/or recycle unwanted chemical materials. It is now thought that we can harness this process, and use our cells own molecular ‘garbage trucks’, as Prof. Rubinsztein calls them, to rid the brain of mutated proteins in disease.
‘I think there are likely to be a set of unifying mechanisms in different brain diseases’, said Prof. Rubinsztein, ‘Targeting protein aggregation is very appealing. I think one’s got to look for the unifying mechanisms – that helps you prioritise what’s the most important angle to chase’.
With such an array of cutting-edge research and distinguished minds in this field, it certainly feels like we’re now hot on the heels of brain diseases. And as public engagement becomes increasingly important to bridge the divide between science and the public’s perception of science, events like this are creating essential space for discussions from all perspectives. There is undoubtedly tremendous scope for the continued advancement of science in the public domain, and as scientists the onus rests on us to help carry this undertaking forward.
For more information on the NDI, visit Degenerating Neurons: .