New gene therapy targeting C9orf72-ALS begins Phase 1 clinical trial in the UK

This article was written by Dr Keith Mayl and Dr Ahmad Al Khleifat of King’s College London.

Researchers at King’s College Hospital, led by Professor Christopher Shaw, have embarked on the first gene therapy clinical trial for patients affected by a specific genetic form of ALS, the most common type of MND.

ALS is a progressive disease in which the nerves controlling muscle movement, known as motor neurons, degenerate resulting in muscle wasting and weakness. In about 10% of people the cause is a mutation in the C9orf72 gene. This mutation results in the formation of toxic products which are harmful to motor neurons. People with the mutation typically develop symptoms in their 50s, starting with speech and swallowing problems, followed by weakness of the arms, legs and breathing. It is also linked to problems with language and behaviour and is the most common genetic cause of frontotemporal dementia.Read More »

Life of an MND researcher – part 2: PhD edition

Each year, the MND Association dedicates the month of June to raising MND awareness. This year, we focus on the eyes – in most people with MND the only part of their body they can still move and the only way left for them to communicate. Alongside the Association-wide campaign, the Research Development team selected six most-enquired about topics, which we will address through six dedicated blogs.

In our previous article we introduced four MND researchers who gave us an insight what a typical day in the life of a researcher looks like and what carrying out a research study actually involves. In this continuation article, you will get the chance to look into the lives of four PhD students, who give us an overview of their projects and their usual daily duties.Read More »

ANXA11 – another gene closer to understanding ALS

A new research paper has been published today in the Science Translational Medicine journal, describing a new gene implicated in developing MND. What is this gene and why is it important for our fight against MND?

Although they are not the sole cause of MND, genes play a big role in someone’s probability of developing the disease. A number of such genes that make a person susceptible to developing MND have already been identified, with most of them causing the rarer, inherited form of the disease.

A new addition to a list of genes that are related to development of ALS, the most common form of MND, has been discovered by researchers from King’s College London. Dr Bradley Smith and colleagues screened genetic data of an unusually high number of people of European origin: 751 with inherited – familial – ALS (fALS) and 180 with non-inherited – sporadic – ALS (sALS). Detailed analysis of this data found that specific mutations in the ANXA11 gene are associated with around 1% of all fALS and 1.7% of all sALS cases.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 »

Our Visit to a Brain Bank

Brain banks are a vital resource in MND research. The MRC London Neurodegenerative Diseases Brain Bank was established in 1989. It is part of King’s College London and King’s College Hospital, and is part-funded by the Medical Research Council (MRC).

The new brain bank building at King's
The new brain bank building at King’s

After 18 months of planning, the bank has recently relocated into a bright terracotta building, fit with state-of-the-art equipment and plenty of space to teach in.

To celebrate the move, my research team colleague Martina and I attended their open day. We heard some interesting talks then got to meet the team, tour the labs, and even see a brain dissection! Here’s what we found out…Read More »

New fellowship to investigate muscle fasciculations

During Awareness month in June we reported on the work of Dr James Bashford at King’s College London, exploring new ways of measuring muscle fasciculations in people with MND. The results from the one year pilot study have shown a lot of promise, which has led to Dr Bashford recently being awarded a Clinical Research Training Fellowship.

A common symptom of MND is the ‘rippling’ of muscle under the skin, these are known as muscle fasciculations.Read More »

New genetic discoveries tell us more about what causes MND – Part 1

Today some exciting news about the genetics of MND was published in the scientific journal Nature Genetics. The results come in two research papers published in the same issue of the journal.

This blog post discusses the results of the first of these papers for which King’s College London based Professor Ammar Al-Chalabi was one of the leading researchers. A post on the second paper will follow later.

Here we’ve given an overview of what the researchers have found, what it means for people with MND and how the analysis was conducted. You can read a more detailed explanation of the research results from the King’s press release.Read More »

Using surface EMG to see if fasciculations can be used as a biomarker for MND

What are fasciculations?

When motor neurones in the spinal cord become damaged this makes them electrically unstable, meaning they spontaneously discharge electrical impulses that cause small groups of muscles to contract. These contractions, known as fasciculations, are a common symptom of MND. Research suggests that they might be a good marker of motor neurone health.

Tracking fasciculations with surface EMG

Prof Chris Shaw
Prof Chris Shaw

Led by researchers Prof Chris Shaw and Prof Kerry Mills, Dr James Bashford is using technology called surface EMG to collect data on the site and frequency of fasciculations in different muscles in people with MND. Fasciculations in people with MND are different to benign fasciculations, which can occur in people without the disease and are generally harmless. James and the team hope to show that fasciculations in those with MND have a unique ‘fingerprint’ which can be accurately identified and tracked.

Data collected will be compared to other information currently used to track the progression of MND. James and the team hope surface EMG might provide a more sensitive way of measuring disease progression than previously used methods. This one year feasibility study is being carried out at King’s College London at a cost of £95,000 (our reference: 932-794).Read More »

Using DNA Bank samples to create iPSC models of MND

Induced pluripotent stem cell (iPSC) technology has enabled researchers to create and study living human motor neurones in the lab, derived originally from patient skin cells.

DNABankLogoThis project (our reference 80-970-797) is a collaboration between the labs of Professors Chris Shaw and Jack Price at King’s College in London and Siddharthan Chandran in Edinburgh. It aims to use the already collected white blood cell samples within the UK MND DNA Bank to create a larger number of new iPSC models of MND. Ultimately creating an MND iPSC cell bank, these models will enable researchers to better understand the disease and screen potential new drugs.Read More »

Investigating C9orf72 and TDP-43 proteins in a fruitfly model of MND

Background to C9orf72 toxicity

We know that damage to C9orf72 (both the gene and the protein it makes) is a crucial step in why some people get MND and why some people get frontotemporal dementia. There are three possible reasons why C9orf72 is toxic. 1) the way the gene is damaged alters how it normally works. 2) the formation of clumps of RNA – a by-product of the damage and not normally seen in cells, and 3) the formation of very short, new and unwanted proteins called ‘dipeptide repeats’ or ‘DPRs’, again these are not normally seen..

There’s evidence of all three types of toxicity within the motor neurone, but we don’t know how they work together or if one is more toxic than another. We also know that the protein TDP-43 forms clumps in motor neurones affected by the C9orf72 gene.Read More »