The fifth session of the ENCALS meeting focussed on the role of TDP-43 in ALS.
The first talk during this session was given by myself (Jakub Scaber, MRC/MND Association Lady Edith Wolfson Fellow, University of Oxford). I was given the opportunity to present neuropathological data from the Oxford Brain Bank.
Our study reaffirmed previous findings of the central role of TDP-43 pathology in C9orf72 cases as a common pathway between FTD and ALS cases. We were able to show that TDP-43 pathology at post-mortem correlated very well with the disease phenotype during life, more so than GA dipeptides and sense foci, which are direct pathological consequences of the hexanucleotide repeat. There was some increased GA dipeptide burden in disease-relevant areas of patient brains who had FTD during their lifetime, and sense foci were ubiquitously present in all cells. How the C9orf72 pathology and the later TDP-43 pathology are linked remains a key question in the investigation of this mutation. Continue reading →
Friday saw the highly anticipated publication of results from the ProGas study, which was part-funded by the MND Association.
I manage the publication of evidence-based information resources for health and social care professionals at the MND Association. I can’t recall a time when I’ve felt so much pressure to delay publishing a resource due to emerging findings. Continue reading →
The ENCALS meeting this year has been held at Trinity College in Dublin. This suggestive place hosted more than 250 participants and several international guests as the eminent researcher Prof. John E. Landers,Professor of Neurology at University of Massachusetts, who opened the “Genes and Genomics” session with a talk entitled “Using Next-Generation Sequencing to Dissect Amyotrophic lateral sclerosis (ALS) Pathogenesis”. Prof. Landers pointed out how the investigation of rare variants are important in the discovery of pathways underlying the neurodegenerative mechanism of rare diseases and how exome sequencing became an important strategy for identifying human disease genes by spotting rare variants.
This year Dublin was not only home to the annual ENCALS meeting 2015, but also to a referendum on gay marriage. One week after the meeting the buzz of the sessions is still with me. This was an excellent event and the varied scientific sessions and posters helped to build my knowledge and understanding of research into the causes and consequences of ALS/MND. Time spent in Dublin also gave me many exciting opportunities to network with colleagues across Europe. Here is an outline of the ENCALS 2015 cognition session.
The session was chaired by two inspiring ladies and world’s leading MND researchers, Prof Sharon Abrahams from University of Edinburgh and Dr Marwa Elamin from Trinity College Dublin. Continue reading →
Leonard Petruccelli commenced the session discussing mechanisms of toxicity and therapeutic approaches for C9FTD/ALS, beginning by highlighting the enormous advancement in the understanding of the genetics and neuropathology of FTD and ALS since 2006. The three proposed mechanism of C9orf72 mutations were presented; 1) a gain of toxicity as a result of RNA foci in cell nucleus, 2) haploinsufficiency and 3) dipeptide repeat (DPR) protein toxicity. Around 20 diseases contain RNA repeat expansions however repeat associated non-ATG translation (RANT) of the C9orf72 hexanucleotide repeat expansion was seen to be specific to the brain with anti-C9 RANT immunoreactivity specific to C9FTD/ALS patients. Continue reading →
The biggest ALS European meeting was held this year in Dublin, Ireland. Due to unforeseen circumstances, the venue (i.e. country and city) had to be changed last minute from Milan, Italy. Nevertheless, Dublin as a city was riveting and impressive, which was further augmented by the electric atmosphere created by the same-sex marriage referendum that took place during the dates of the ENCALS meeting.
The Cognitive session will be my focus here and Prof Sharon Abrahams and Dr Marwa Elamin chaired it. The session opened with a quick introduction and an important highlight that this marks the very first Cognitive session ever held at ENCALS. While the session was mostly about Cognition in ALS (being true to its name), it was riddled with behavioural aspects of functioning as well. Continue reading →