Mice and Marbles: A CRISPR Model of Motor Neurone Disease

In a study published in Nature Neuroscience this week, a collaboration led by Dr. Jemeen Sreedharan and colleagues from King’s College London, the Babraham Institute and the University of Cambridge have published a new mouse model of Motor Neurone Disease (MND).

The study takes advantage of cutting edge gene editing technology called CRISPR/CAS9 to generate a mouse model of the human disease that accurately mimics a genetic component found in some people affected by MND. The researchers used the gene editing technology to precisely change (mutate) the gene that the body uses to produce the protein TDP-43, a very important player in the MND story implicated in almost all cases of MND.Read More »

Standing on the shoulders of… Dorothy Hodgkin

On the way to work last Wednesday, a story on BBC Radio 4 – ‘Today programme’ suddenly grabbed my attention: “February will mark the 100th anniversary of women having the right to vote!”

Curiosity sparked, I turned up the radio: “BBC Radio 4 are holding an online vote for the most influential British women of the past century. Each day in the run up to the anniversary we’ll be shortlisting and celebrating a candidate for the award”.

Last Wednesday’s nominee was Dorothy Hodgkin, the only British woman to ever win a Nobel Prize in the sciences. Dorothy won her award in 1964 for developing a technique that enables the complex structure of proteins to be deciphered – this is known as protein crystallography. Dorothy used this technique to work out the structure of insulin, vitamin B12 and penicillin.

Funnily enough, I had recently been discussing this technique with my colleague Jessica. I told her the news story when I got to work and we decided we’d share with you how, thanks to Dorothy’s brilliant work, protein crystallography is currently helping researchers funded by the MND Association to find out more about MND.Read More »

It’s not just about the neurones

Long before the latest wave of cellular and molecular biology advances started to give us new information on what was going on at the cellular level in MND, some doctors had observed that if the disease started in one particular part of the body, it would be neighbouring parts that became affected next.  This suggested that the disease usually starts in a single part of the brain or spinal cord before spreading further, like ripples in a pond.

How this happens is not well understood. It is likely that there are a number of processes going on, but they can broadly be divided into two theories. One of these is that damaged proteins can leak out of sick neurons and ‘infect’ their neighbours – a subject we have discussed at previous international Symposia.Read More »

Libraries, Doormen and Harry Potter

I usually travel to London two to three times a month for meetings and lab visits. If I’ve got any length of spare time, I head for what I call my ‘London office’ – aka the British Library. It’s close to Euston station, it’s free (!) it has a nice café for informal meetings and it has copies of all the latest textbooks and major research journals.

The way in which a cell turns its genetic instructions into the protein ‘building blocks’ it needs to function and survive is sometimes compared to a library.Read More »

Lighthouse Project shines a beacon on HERVs and their role in ALS

There is recent evidence to suggest that Human Endogenous Retroviruses (HERVs) may be involved in amyotrophic lateral sclerosis (ALS). HERV-K has been directly linked to motor neurone damage and has been found in the brain tissue of patients with ALS.

The MND Association recently awarded a small grant to fund part of the ‘Lighthouse Project’ which is investigating the safety and any beneficial effects of an antiretroviral drug on ALS symptoms.Read More »

Networking to progress in the world of science: Mini-Symposium on MND

Conferences and symposia are a crucial part of the research world – not only for the amount of knowledge that is communicated to large audiences but also for the exchange of ideas on a more inter-personal level. Novel ideas are created there as well establishment of collaborations that might lead to new research projects and clinical trials – all in all, putting a bunch of researchers in a venue with a projector, coffee and biscuits can only lead to good things!

One of the recent events that I had the pleasure to attend was a small-scale conference – the Mini-Symposium on generic disease mechanisms in MND and other neurodegenerative disorders. Held at the Brighton and Sussex Medical School in late June, this event was a precursor to the inauguration of a new MND Care and Research Centre for Sussex, directed by Prof Nigel Leigh.Read More »

Investigating the role of the cell’s waste disposal systems in TDP-linked MND

In April 2016, Dr Jackie Mitchell gave a talk at the Regional Conference in Gatwick to explain the aims of her three year MND Association funded research project. We have now received her second year report. In this blog we explain a little bit more about what she’s been doing. She has already made some good progress.

A little bit of background
One known genetic cause of MND is a defect in the TARDBP gene, which makes the protein TDP-43, that can be found in the nucleus of a healthy cell. The nucleus is the part of the cell that contains all our DNA. Healthy cells also have two major ‘waste disposal systems’ which break down and remove unwanted proteins from cells. More information on the role of TDP-43 in MND can be found on our blog.Read More »

New ALS review article available

ammar2.jpgLast week, The New England Journal of Medicine (NEJM) published a review article by Professors Ammar Al-Chalabi and Robert Brown, in which they looked at the up to date evidence on the incidence of ALS, pathological mechanisms of the disease, as well as genetics and therapeutic strategies.

We would very much like to thank the NEJM who kindly allowed us to share full text of this article on our website – this is now available to view here.

Closing the door on toxic proteins – new clues in understanding a genetic form of MND

The defects in the C9orf72 gene are known to cause motor neurone disease, but researchers don’t understand why. Defective copies of this gene are passed down in some families affected by the rare, inherited form of MND. This week MND Association grantees Drs Guillaume Hautbergue, Lydia Castelli and colleagues, based at the Sheffield Institute of Translational Neuroscience have published their research study providing some important clues about the toxicity of C9orf72. Their research is published in the prestigious journal Nature Communications.Read More »

Exploring the interaction between TDP-43 and RNA

In light of the upcoming Biomedical Research Advisory Panel meeting happening on Friday 7 April that will discuss which new research projects the MND Association will fund, we are pleased to report on the progress of one of our already-funded researchers. In their three year project, funded by the MND Association, Prof Annalisa Pastore (King’s College London) and Prof Gian Tartaglia (University Pompeu Fabra, Barcelona) are investigating the process by which TDP-43 binds to RNA. Below is a summary of the progress they made during their first year.

Background to the project

Alumni Board Meeting 2008
Annalisa Pastore, King’s College London

One of the causes of amyotrophic lateral sclerosis (ALS), the most common type of motor neurone disease (MND), is related to faulty functioning of the TDP-43 protein, a component that is naturally present in all of our cells. In healthy cells, TDP-43 resides in the centre of a cell (the nucleus) where it attaches to RNA and supports correct gene expression – that is, it helps to extract information carried by a gene to form proteins, the main building blocks of our bodies.

Read More »