2016 International Symposium - Dublin · biomedical · Insights · Scientific

Session 7C: Mouse Models


At the beginning of December 2016, hordes of research scientists and clinicians embarked upon Dublin, a.k.a. the ‘home of Guinness’, for the 27th International Symposium on ALS/MND. This was my second conference and the Dublin Convention Centre on the north bank of the river Liffey was a great setting.

Session 7C focussed on mouse models of ALS and ALS/FTD. The five talks really highlighted the genetic heterogeneity of these diseases and the importance of generating multiple models to investigate both potential molecular mechanisms underlying the disorder, and novel therapeutics.

The first two talks focussed on the generation of mouse models as a tool, with the potential to investigate mechanisms leading to neurodegeneration and therapy development. The first talk (C66) discussed a new Chmp2B mouse model of ALS/FTD, which harboured a Chmp2Bintron5 mutation, the main mutation found in FTD patients. They showed through a variety of biochemical, histological and behavioural data that these mice have many features of ALS/FTD including; decreased survival, motor dysfunction and behavioural changes. The next talk (C67) focussed mainly on the gene C9orf72. They examined AAV9-mediated expression of the (G4C2)n repeat expansion and dipeptide repeat (DPR) proteins associated with disease in both cells and mice. Interestingly, they found that expression of DPRs alone was sufficient to result in C9orf72-linked pathology and motor dysfunction in mice, starting in the first 4 months after injection of the virus. It will be of great interest to see what these two models may discover in the future.

The next talk (C68) highlighted how mouse models can be used to further understand the mechanisms underlying disease, in particular the role of serotonergic neurons. One of the findings they reported was that when SOD1 was selectively deleted in the serotonin neurons of the brainstem in adult mice, the degeneration of serotonin neurons was rescued and abolished spasticity in these mice. This provides useful insight in to the role of serotonergic neurons in disease for the future.

The last two talks focussed on how mouse models can be used to identify disease modifying therapies. The talk (C69) discussed the potentially disease modifying effects of exercise. From their work in the SOD1 mouse model, they concluded that reduced activity following a diagnosis of MND may impact negatively on disease progression, as it exacerbated disease progression in the mice. However, they also reported that increased activity did not slow progression of disease either.

The last talk (C70) discussed the effect of a α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist in an AR2 mouse model, which usually shows ALS phenotypes including TDP-43 mislocalization. The treatment decreased the progression of observed ALS phenotypes and appeared to reduce TDP-43 pathology. This particular compound has already been approved as an anti-epileptic drug, suggesting it could be repurposed as a potential candidate drug for an ALS clinical trial.

To find out more about all the research from the symposium, you can find the abstracts on http://www.mndassociation.org/research/international-symposium/abstracts-online/.

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