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 »
Recently published results from the open-label Lighthouse trial investigating safety of the drug Triumeq in people with MND revealed the treatment was safe and ready to progress to a larger Phase 3 clinical trial.
The trial was held in Australia and recruited 40 people with MND who all received the active drug; this was because the aim of the trial was to see whether Triumeq, which is already licensed to treat HIV, has a potential as a treatment for MND.
Why HIV drugs?
One of the possible triggers of MND has been suggested to be a group of ‘fossil’ viruses that, over many millions of years of evolution, have left traces of their DNA within our genome. When activated, these ‘retroviruses’ have the ability to merge into our cells, by copying their DNA into our genome, which leads to incorporation of the two DNAs into one. When the affected cell then creates new proteins, partial copies of the virus are produced with it.
Retroviruses have been linked to MND because of findings of a particular retrovirus, called human endogenous retrovirus (HERV-K), in the brains and motor neurons of people with the disease. Although some studies failed to confirm this finding, researchers deemed this to be a promising area of therapeutic focus.Read More »
“The annals of ALS clinical trials is strewn with failed studies. Only two out of more than 70 clinical trials have been positive, and even these showed only very modest benefit. Is this dismal record strictly due to the extraordinary complexity of neurodegenerative disease in general, and ALS in particular? Or is it due to methodological flaws that could be repaired?”
Robert G Miller, Professor of Neurology, Stanford University
Although there is not much we can do about disease complexity, improving the way treatments are trialed is something that can be achieved. Imagine a world without clinical trials, where independent companies or individuals would be allowed to sell their self-made ‘drugs’ without any evidence that they were ever used on anyone with the disease, let alone that they would improve one’s condition. No one would know what the drug is (which could simply be a water solution), how it works and whether as soon as the drug is taken, we would be poisoned.
Thankfully, this is not the case and clinical trials, although not perfect, are considered the gold standard for approving any treatment. However, there are still some improvements that can be done to make trials easier to access and provide more accurate estimates of drugs’ effectiveness much faster.
This blog is part of the ‘Highlights from Glasgow’ collection of articles, where you can read about the content of some of the talks and posters presented at the 29th International Symposium on ALS/MND.
In the Clinical trials and trial design (4B) session we heard from two speakers looking at ways to improve current design of clinical trials. In his plenary talk, Mahesh Parmar (C20) provided his perspective on the necessity of changes from his experience working on cancer trials, highlighting that any efforts to improve clinical trials should be focused on Phase 3 where the most money and time is spent. One solution that stuck with a lot of clinicians attending Prof Parmar’s talk was the design used in the STAMPEDE trial, a large clinical trial assessing effectiveness of new treatments for people affected by prostate cancer, which has been running since 2005. The innovation of this approach is the ongoing protocol that allows to test multiple treatments within the same established clinical trial, allowing new drug candidates to be tested (relatively) straight away, avoiding the creation of a brand new clinical trial. This design improves efficacy of testing new treatments, systematic approach to testing, and access to a large pool of participants who could take part in multiple treatment trials over time.
Brian Dickie, the Director of Research Development at the MND Association said: “Prof Parmar’s presentation generated a lot of interest amongst clinicians who are regularly involved in MND trials and there was a strong feeling that this is the direction that we need to be taking with MND as it could increase the efficiency and reduce the cost. That said, it will take a while to put the building blocks in place and we certainly wouldn’t want to hold up trials that are already in advances stages of planning, so I would expect to see a gradual introduction of changes to trials design over the coming years.”
In the last decade, the MND Association has invested millions in research within the UK and across the world. We are a leader in the funding and promotion of cutting-edge MND research and, with over 30 years experience of identifying the most promising projects, we only fund and support scientific and medical research of the highest quality and relevance to MND.
And the great news is, we are not the only ones!
The International Alliance of ALS/MND Associationshas 54 member institutions, in 40 countries around the world – from Mongolia to Mexico, Malta to Malaysia – who are supporting, funding, collaborating in and carrying out MND research, and/or offering much needed care and support to people with MND and their families.
All the institutions listed by the Alliance are shown on the map above. If you want to take a look at some of these, they are easy to access through the International Alliance website. Some of the websites are not in English but you can use the Google Translate Web tool to translate the entire site into English (or any other language).
So let’s take a whistle-stop tour and explore some of the latest research and support projects that other institutions around the world are involved in. The institutions I mention are shown on the map with a yellow pointer.Read More »
As well as all the networking, debate and new information being shared, the International Symposium on ALS/MND is also a time to celebrate achievements by the giving of awards. The Biomedical and Clinical poster prizes are an opportunity to recognise and celebrate the excellent research and clinical practice being conducted by those early in their career.
Now in its fourth year we hope that the poster prizes will help give the winners career a boost, and give them the encouragement and motivation to continue in MND/ALS research. This year the Panel selected an international group of winners: Dr Albert Lee from Australia and Elsa Tremblay from Canada were jointly awarded the Biomedical poster prize and Ruben van Eijk from The Netherlands won the Clinical poster prize. Each winner received a certificate and a glass engraved paperweight.
The prize winning research ranged from understanding the consequences of a newly discovered gene mutation linked to MND, to why the junction between nerves and muscles is one of the earliest signs of motor neurone damage, to a new statistical analysis to make clinical trials quicker and more efficient. Below I’ve explained more about the research that the winners presented.Read More »