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 »

FaTHoM 2: UK-leading MND clinicians on inherited MND

After its successful premiere in 2017, the University of Oxford organised another meeting of people affected by inherited MND, called ‘Families for the Treatment of Hereditary MND (FaTHoM)’. This turned out to be yet another excellent day where MND clinicians-researchers presented on topics such as genetics of MND, genetic testing and gene therapies. Below you can find out more about what was presented on the day and links to the videos of recorded talks.

Understanding familial MND

Introducing the rationale of the meeting, Prof Martin Turner set the scene by explaining the great difficulty in understanding the disease due to its many possible causes. Being such long cells, many things can go wrong in the motor neurones and in the vast amount of their support cells (such as astrocytes or microglia). But one factor can help us understand the disease better – genes.

Around 5-10% of MND is considered familial. That is, around 1 in 15 people have had someone in their family affected by this disease in the past, making them more likely to develop the disease themselves. Specifically, if we consider the ‘multistep hypothesis’ of MND which assumes that six steps have to happen in our lifetime for the disease to develop, a mistake in a specific gene may reduce the number of the necessary steps to four or even two (read more about the impact of genetic on the multistep hypothesis here).Read More »

Update on gene therapy approaches to treating neurodegenerative disease

Every day there are two sets of talks going on at the same time during the International Symposium. On Saturday morning there was a symmetry to what was being discussed in these parallel sessions. Both were talking about the inherited form of motor neurone disease (MND). One as reported from Sara’s blog was from the clinical perspective of talking through the possibilities and implications of having a genetic test, if the inherited form of MND runs in the family. I was in the other set of talks going on – exploring ways to develop treatments for inherited MND.

For those with inherited MND there are not currently any treatments to prevent the effects of the gene damage that is being passed from one generation to the next. However, research is underway to find such treatments. As these treatments are, by definition, designed to alter how these faulty genes work, they’re collectively known as gene therapy.

Different approaches in gene therapy

All three talks in this session of the symposium talked about a different, complementary approaches. Adrian Krainer spoke about ways to alter how genes are read. In the following presentation Brian Kaspar explained his research into ways to get copies of the healthy, unaffected gene into the body and working to counteract the damaged gene. They both showed how gene therapy might work in the neuromuscular disease spinal muscular atrophy (SMA), however the principals of how they work can be applied to MND.Read More »

Posters, posters!

During the 25th International Symposium on ALS/MND there were two dedicated sessions for researchers to view over 300 posters. These posters varied from brain imaging to therapeutic strategies. But what is a poster? In this blog I’ll explain more about the session, as well as highlight some of my personal favourites.

Dr Jakub Scaber next to his poster in Brussels
Dr Jakub Scaber next to his poster in Brussels

A biomedical or clinical poster, is in many ways, like an advertising poster. Researchers use colour and text to present their research in a visual way, to engage and discuss their work.

This year’s poster sessions during the symposium were extremely busy, with large crowds often surrounding just one poster and its presenter! The whole room was a real ‘buzz’ of excitement with poster presenters benefitting from the interest and discussion of their work from researchers around the world.

Our Lady Edith Wolfson Clinical Research Fellow, Dr Jakub Scaber (University of Oxford) said: “I didn’t expect such an interest in my work, I ended up being in discussions for well over half an hour – I didn’t even get chance to remove my coat! I really enjoyed the symposium and got to speak to a few more people than I did last year!” Read More »

Sheffield work towards a treatment for SOD1 form of MND

A number of articles were published in various news sources on 11 July 2014, highlighting how scientists in Sheffield are working towards testing a promising treatment for a rare inherited form of MND caused by the SOD1 gene. Here we write about the research and what it means for people living with MND.

The Sheffield Institute for Translational Neuroscience (SITraN) specialises in research into MND and other neurodegenerative diseases. Recently the institute received an anonymous donation of £2.2 million to help translate their research from the lab to the clinic. This is a huge amount of money into MND research and this donation will enable the researchers to further our understanding of the disease.

Laboratory PhotoThe research

We know that approximately 10% of cases of MND are inherited. This means that they are characterised by a strong family history and the disease is caused directly by a mistake in a specific gene. Of these 10% of cases, 2% are caused by the SOD1 gene (meaning that for every 100 cases of MND, 10 cases are inherited and of these, only 2 are directly caused by the faulty SOD1 gene).

Prof Mimoun Azzouz’s research at SITraN was reported in a number of news outlets, highlighting how his research is paving the way to a treatment for a rare form of MND. His research is at a relatively early stage, where he has only just begun investigating the use of a technique known as ‘gene therapy’ in mice affected by the SOD1 inherited form of MND. If the research goes to plan, he will be able to submit a proposal for regulatory approval by August 2015.Read More »

Using induced pluripotent stem cells to further our understanding of MND

Dr Jakub Scaber from the University of Oxford is our newest Medical Research Council (MRC)/ MND Association Lady Edith Wolfson Clinical Research Fellow. He is investigating how the newly identified C9orf72 gene causes MND in some individuals using induced pluripotent stem (iPS) cell technology.

Courtesy of Prof Chandran's laboratory, University of Edinburgh
Courtesy of Prof Chandran’s laboratory, University of Edinburgh

Researchers funded by the Association were amongst the first to create human motor neurones from donor skin cells, mimicking the signs of MND. Today, the Association is committed to funding six research projects using iPS cell technology to further our understanding of MND. This includes the recently awarded fellowship to Dr Scaber. Read more about these projects here.

Dr Scaber will be using iPS cell technology to take skin cells from someone living with the rare inherited form of MND (5 – 10% total MND cases) caused by the C9orf72 mutation. Similar to Prof Chandran’s research at the University of Edinburgh, he will then make these cells ‘forget’ what they are and turn them into motor neurones. By studying these cells in detail he aims to find out how this mutation causes MND and whether or not gene therapy can be used as a potential treatment.

Read More »