Yesterday I attended the Engineering and Physical Sciences Research (EPSRC) Council’s Town Hall meeting about their Healthcare Technologies ‘Grand Challenges’. These ‘Grand Challenges’ form part of their recently-announced new strategy for their Healthcare Technologies theme.
The aim of the meeting was to outline the new strategy and to raise awareness of some new opportunities to begin to implement it. The audience included researchers from academia and industry, and those that might be the end users of this research – medical charity representatives.You can see a nice diagram of how the Healthcare Technologies theme fits with EPSRC’s overall strategy on their website. Elsewhere on their website you can read more about the new Healthcare Technologies strategy. Continue reading
In Summer of 2014 a new member joined the team at the Sheffield Institute for Translational Neuroscience (SITraN) to work towards identifying new treatments for ALS/MND – Professor Winston (Win) Hide arrived from the Harvard School of Public Health, USA. Since that time I have had the pleasure of working with Win and I thought, on the occasion of his inaugural lecture, I would share some thoughts about what he brings to Sheffield and to the ALS/MND field.
Win is an expert in Biostatistics. At SITraN we work with a large spectrum of cell and animal models as well as with material kindly donated by patients such as blood and skin samples. The work performed on these samples can be very specific – for example, what happens if I take away this or that molecule? But increasingly we also want to ask more open-ended questions – what is wrong with this particular cell? If a neuron from a patient with ALS/MND could tell us what is happening within it, what would it say? This is where Win’s expertise comes in; he has a long track record of asking these open-ended questions in a variety of fields and with a lot of success: http://www.sheffield.ac.uk/neuroscience/staff/hide.
To explain a bit more: each cell within the human body is a hugely complicated system full of genes and proteins working together. What Win is particularly good at is using information about how these genes and proteins have worked together in the past – utilising a broad range of datasets from a broad range of systems – to work out what is broken in ALS/MND. An example of this is the Pathprint tool (http://genomemedicine.com/content/5/7/68) which allows a researcher to take gene expression data from a particular sample, which can be large and unwieldy, and calculate the level of activity across a set of known and understandable biological functions and pathways. Genes and proteins do not work alone and approaches which do not include this integration can miss important data. Already this methodology is yielding new insights in the mechanism of disease in ALS/MND and will hopefully lead us to new and effective treatments in due course.
Win and I are working towards the identification of a dysfunctional signature common to all forms of ALS/MND. We know that ALS/MND can have a variety of different causes, some genetic and some probably environmental. However, in the end all forms of the disease have some common features, such as the death of motor neurons. We want to use the tools Win has developed to characterise this ‘final common pathway’ and ultimately design treatments to reverse it.
On a personal note working with Win is a pleasure. He is fun, hard working and intelligent. We have just started another stage of the journey towards understanding and treating this terrible disease.
Growing evidence suggests dysregulated autophagy contributes toward several neurodegenerative diseases, including ALS and FTD. In the session 7A – genetics and genomics, Professor John Hardy from University College London highlighted that many ALS causing mutations occur in genes that regulate autophagy. In addition, accumulation of misfolded protein in motor neurons is a pathological hallmark of the disease, and is suggestive of autophagy incapable of clearing protein aggregates. Continue reading
Discussion of respiratory management in caring for ALS patients is essential for their comfort, health and end-of-life decisions. This session covered a range of information from original diagnosis of respiratory failure, use of a diaphragm pacing system and experiences of termination or failure of ventilation from the perspectives of health professionals working in ALS centres in Germany, Ohio USA, and the UK. Continue reading
Modelling a complex condition such as ALS in a laboratory is an understandably difficult concept, and it is perhaps unsurprising that we don’t yet have the perfect model. This session early on a Saturday morning looked at the different approaches to using cells in the lab to investigate ALS.
The first speaker and one of the chairs of this session, Dr Kevin Eggan from Harvard, started us off by describing how iPSCs (induced pluripotent stem cells) can be a useful tool in the study of ALS. The technique for creating and using iPSCs was excellently reviewed by Dr Eggan in Neuron (2011; 70(4):626-44). Patient cells exposed to different growth factors can be reverted to a pluripotent state and then turned into motor neurons, with the added benefit of retaining any genetic markers from the patient.
How iPSCs can be produced from different people to take advantage of genetic variations
The last scientific session for the symposium was on non-neuronal cells and comprised of speakers from around the world.
Professor Hugh Perry (Southampton, UK) gave the first presentation. He discussed the commonality between various neurodegenerative diseases and the role inflammation, microglia and macrophages play. In neurodegeneration, microglia proliferate and are primed by the molecules CSF-1 and IL-34. Microglia are considered dynamic cells and can be primed by systemic inflammation that switches the innate response to an aggressive tissue damaging phenotype, which further contributes to disease progression. ALS can be described to have common features with Alzheimer’s disease and CJD; they are progressive and fatal neurodegenerative diseases that accumulate misfolded amyloid and exhibit a predictable ‘prion-like spread’ of pathology. Moreover, there is an increase in the numbers of activated microglia, which indicates underlying neuroinflammation. Continue reading
Linda Greensmith from UCL, UK and Bradley Turner from the Florey Institute, Australia chaired one of the final sessions for Saturday on Murine Models. With the number of causative genes increasing over the last 20 years it is critical to understand the disease mechanism for each gene to progress understanding of the disease and more importantly, to identify novel therapeutic targets. As such, there are increasing numbers of murine models of ALS that contribute to our understanding of ALS. Continue reading