Thursday 10th December - Centre Researcher ALS Symposium Presentations

The following pieces of research are being presented today as academic posters, to registered participants at the MNDA Virtual International Symposium on ALS, between 5.10pm and 5.50pm.

The full event is running from Wednesday 9th - Friday 11th December. 

Factors Impacting Trial Participation in People with Motor Neuron Disease: A Protocol

Presented by Emily Beswick

Authors: Emily Beswick, Michael Wong, Juan Larraz, Rachel Dakin, Siddharthan Chandran, Judy Newton, Alan Carson, Sharon Abrahams and Suvankar Pal

This study looks at how changes in mood, thinking, attitudes and physical ability affect a person with MND’s decision to participate, and remain in, a clinical trial. The purpose of this study is to improve our understanding of why people with a diagnosis of motor neurone disease (MND) choose to participate, or not participate, in clinical trials of potential new drugs. We will also look why individuals with MND who are participating in a clinical trial may stop participating in that trial.

International evaluation of current practices in cognitive assessment for amyotrophic lateral sclerosis 

Presented by Debbie Gray 

Authors: Debbie Gray and Sharon Abrahams 

Changes in cognition and behaviour are prevalent in up to 50% of people with ALS. We found that cognitive assessments have been implemented into ALS clinics around the world, with the Edinburgh Cognitive and Behavioural ALS Screen (ECAS) being the most popular test used. Screening for cognitive and behavioural changes has benefits for clinicians, patients, and carers, and is viewed as having a positive impact on clinical care. 

Investigating neuroinflammatory dysregulation and its implications for disease phenotype and progression in C9orf72 post-mortem tissue

Presented by Olivia Rifai

Authors: Olivia Rifai, Poulomi Banerjee, Sharon Abrahams, Siddharthan Chandran, Chris Sibley and Jenna Gregory

This research focuses on how inflammation could be affecting disease duration in C9orf72-associated ALS, and includes both immunohistochemical and NanoString molecular barcoding data.

Life ‘on high alert’: how do people with a family history of MND make sense of genetic risk? Insights from an online forum.

Presented by Jade Howard

Authors: Jade Howard, Fadhila Mazanderani and Louise Locock

Based on an analysis of posts from an online forum, Jade’s research seeks to understand how people with a family history of MND make sense of and negotiate genetic risk. It looks at how individuals engage with risk through reconstructing the past, coping with uncertainty in the every day, and looking to the future. It highlights the significance of knowledge based on personal experience, which becomes intertwined with scientific and genetic information.

Novel methodology for producing postnatal spinal co-cultures of astrocytes and neurons for use in the study of ALS

Presented by Sarah Burley and Calum Bonthron,

Authors: Sarah Burley, Calum Bonthron, Matthew Broadhead, Vanya Metodieva, Seth Grant and Gareth Miles

The interactions between neurons in the spinal cord and support cells called 'astrocytes' are critical for the healthy function of the nervous system, and emerging evidence implicates these interactions in disease. Tools to investigate the respective function of neurons and astrocytes are limited, often relying on embryonic mouse tissue where producing cultures of a verified genotype (i.e. +ve or -ve for an ALS mutation) is challenging. To overcome this, we developed a methodology allowing for the production of defined cultures of spinal astrocytes and neurons from postnatal mice, providing a powerful tool for the study of neuron-astrocyte interactions in neurodegenerative diseases such as ALS.

Potential neuroprotective effects in ALS of retinoic acid receptor ligands (RAR-Ms).

Presented by Azita Kouchmeshky

Authors: Azita Kouchmeshky, A Whiting and Peter McCaffery

Azita’s research is based on setting up laboratory investigative procedures (known as assays) representing ALS and then evaluating effects of novel RAR-Ms as an ALS treatment. So far, she has set up a number of cell based assays for drug screening to test RAR-Ms effects on cell pathways assumed to be involved in ALS. The results have shown promising neuroprotection effects of RAR-Ms for treatment of ALS and further investigation of them as a treatment for motor neuron degeneration are ongoing.

Investigating the molecular mechanisms of mutant C9orf72 human iPSC-derived astrocyte-mediated motor neuron deficits

Presented by Maria Stavrou

Authors: Maria Stavrou, Bhuvaneish Selvaraj, Alfonso Bolado, Giles Hardingham and Siddharthan Chandran.

Over the last 20 years of research there has been a strong suggestion that the glia cells (from the Greek word meaning 'glue') that neighbour the nerve cells and support their growth and function, play a central role in the development of MND. Amongst the three types of glial cells, the astrocytes - named for their star-like shape - are the largest and most numerous brain cells in humans compared to all animal species.

Maria generates human stem cells from patients with MND carrying a specific mutation called C9orf72 – this is the commonest genetic cause of MND – and healthy individuals and exploits the latest stem cell technologies to study how astrocytes affect nerve cells in C9orf72-related MND. The more we know about how cells malfunction in MND, the closer we are to understanding how to treat it.