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

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

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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.

Currently, no cure for ALS exists. In 2006 two international groups of researchers led by Professor Christopher Shaw and Professor Ammar Al-Chalabi, both at King’s College London, first narrowed the location of the mutation to a region on chromosome 9. By 2010 Professor Al-Chalabi’s team, working with collaborators worldwide, was able to show that just one of three genes must be the culprit. Eventually the responsible mutation was discovered to be in the C9orf72 gene, and this is now known to be the most common genetic cause of ALS. Since the mutated gene produces toxic products, blocking the gene with gene therapy might be a useful approach to treatment. A phase 1 clinical trial using a novel gene therapy developed by leading pharmaceutical company Biogen, in collaboration with Ionis Pharmaceuticals Inc., is now underway to test this idea.

The gene therapy is a short DNA molecule called an antisense oligonucleotide (ASO) which is capable of selectively binding to and degrading toxic products made from the C9orf72 mutation. The ASO is delivered by injection directly into the fluid which surrounds the brain and spinal cord by inserting a thin needle into the lower spine through a technique called lumbar puncture. The clinical trial is taking place across multiple sites in the USA, Canada and Europe. The aim is to recruit up to 80 patients to take part in this multiple-ascending-dose study to test the safety and tolerability of the ASO. It is currently scheduled to run until 2021 and will aim to test up to 6 cohorts of patients at different doses.

The first dose for the study at King’s College Hospital was successfully delivered by Dr Keith Mayl on Monday 16th September 2019. This is the first gene therapy for a neurodegenerative disease to be trialled in patients at King’s College Hospital. It is a key moment for the motor neuron disease community and if the therapy is successful, will have wider implications for neurodegenerative diseases.

Those wishing to know more about this study and potential recruitment can visit the clinical trial website.

The MND Association’s vision is a world free from MND. Realising this vision means investing more in research, further developing partnerships with the research community, funding bodies and industry, while ensuring that advances in understanding and treating MND are communicated as quickly and effectively as possible. Our Research Development team, composed of 11 members, work hard to achieve this. Principally, the Research Information team within this are involved in communication activities including this MND Research blog.

14 thoughts on “New gene therapy targeting C9orf72-ALS begins Phase 1 clinical trial in the UK

  1. This is fantastic news but I am correct in saying it is the second “gene therapy clinical trial for patient affected by a specific genetic form of ALS”, the first being SOD1 three years ago.
    Which my husband is currently participating in and is lead by Dame Pamela Shaw at SITARN

    1. Hi Valerie,

      Yes, that is correct, and the SOD1 trial is also being ran by the same pharmaceutical companies, Biogen and Ionis.

      Best Wishes,


  2. Hi, my mum in law lives with motor neurone disease, for us to see a possible cure for others in the future brings hope. However recently I attended a training event on ACEs, by Dr Warren Larkin, it was explained that MND can be brought on by child hood trauma. Do you have any information on this as I find it really interesting. Much love and respect Lynne x

    1. Hi Lynne,

      Thank you for your comment and for your support.

      Trauma is one of the possible factors that is being discussed as a potential contributor to the development of MND. We know that MND is caused by a combination of genetic, lifestyle and environmental factors and so combination of these must interplay in order for the disease to develop. It is therefore improbable that one factor on its own would cause MND.

      However, studies are showing that certain traumas might contribute to the development of MND, however, as mentioned above, it is unlikely that the trauma on its own would lead to MND (as there are many more cases of trauma in childhood/adulthood/older age than there are cases of MND).

      If you have any further questions about trauma and MND, please feel free to email us at

      Best Wishes,

      Research Development Team

    1. Hi Sue,

      This trial has just started and so people with the C9orf72 gene variation will be recruited to the trial through their neurologists.

      Best Wishes,

      Research Development Team

  3. Hi, will this trial come to NZ at all.
    Also is it for people who already have the symptoms or who have the gene?

    1. The trial is only open to people who have confirmed familial C9ORF72-MND and these people would have been symptomatic. As far as we know the trial will not be available in New Zealand.

      Best wishes
      Research Development Team

      1. Are NZ Citizens able to travel over of all of this above is confirmed. Or will it be only for those people of that country etc
        Many thanks

      2. Dear poppet3,

        Although it is possible to take part in this trial if you live overseas, it might be quite difficult to do so. In order to be considered for the trial, the person would have to be referred to one of the recruiting sites to be assessed, and if eligible could be put forward for the trial. At the moment the number of people recruited is very small and so recruitment is likely to be taken up quickly by patients local to the site.

        Please also bear in mind that the person would need to be seen regularly to take part in the study, so this may be difficult if the distance is very significant.

        Best Wishes,

        Research Development Team

  4. Hi, my husband has MND but how do we find out which specific form he has? we have asked his consultant but he has told us that there are no different types?, also could you tell me what the criteria is for this trail please.

    1. Dear Karen,

      Generally, MND is an umbrella term for different types of the motor neurones, with the most common form being ALS (Amyotrophic Lateral Sclerosis). It might be possible that your husband’s consultant diagnosed him with ALS, which in itself is a form of MND. Other forms are often dependent on the regions affected, such as progressive bulbar palsy, primary lateral sclerosis or progressive muscular atrophy. You can find out more about the different types of MND on our website here:

      As mentioned in the article, this trial is for people with a mistake in the C9ORF72 gene. Generally, a person can be genetically tested if MND runs in their family – please do read our information sheet B2 for more information. The recruitment for this trial has to go through the person’s neurologist who would liaise with the principal investigators.

      Please also have a look at our Take part in research webpage, where you can find two other clinical trials that are currently recruiting.

      Best Wishes,

      Research Development Team

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