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.
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
Much of the symposium this year involved discussions on the disease associated proteins of MND. This session specifically focussed on the cellular biology and resultant pathology that arises as a consequence of the aberrant functioning of these proteins. Continue reading
Posted on behalf of George Aynsley (Liverpool, UK):
In my final post from the symposium, I report on the End of Life Discussion session:
This was a fascinating session as it brought 3 superb international speakers into the forum. Given the varying legality of euthanasia across countries, a discussion highlighting differing approaches was elucidating. I will first clarify some terms involved in end of life care:
- Euthanasia – killing of patient at request of patient
- Physician assisted suicide – physician provides lethal dose of medication
- Alleviation of pain – provision of medication in such a dose that may reduce life
- Decision not to treat – removal of life-sustaining treatment eg Ventilation