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.
Around the globe, teams are working to find tissue biomarkers for MND and there some promising candidates coming through, some of which were explored at session 8C of the Symposium: Tissue Biomarkers.
We first heard from Rebekah Ahmed (C83), who presented her data on possible neuroendocrine and metabolic biomarkers. Ahmed and her team analysed several proteins related to these systems in the blood of 127 people with either MND or MND with FTD and compared them to controls. The Neuropeptide Y protein (NPY), which is related to eating habits and food intake, was found to be higher in people with MND and MND-FTD, and lower in people with FTD, shining the light on a possible biomarker. All patients also had an increase in leptin and insulin levels, highlighting the need to examine how these neuroendocrine changes affect underlying disease pathology.Read More »
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 »
It has been almost a year since we announced that AMBRoSIA (AMulticentre Biomarker Resource Strategy In ALS) had begun to recruit participants (read the Autumn 2017 edition of Thumbprint).
AMBRoSIA is the biggest project that the MND Association has ever funded and recruitment occurs at three sites throughout the UK (Sheffield, headed by Prof Dame Pam Shaw, Oxford, headed by Prof Martin Turner and London, headed by Dr Andrea Malaspina).
The project will collect a number of biological samples, including blood, cerebrospinal fluid (CSF), urine and skin in order to identify biomarkers (markers of biological change) that could be a signature of MND.Read More »
RNA is the lesser-known ‘cousin’ of DNA – it contains copies of genetic instructions sent out from the nucleus – the ‘control hub’ of every cell. This RNA is carried out of the nucleus by lots of different proteins, including the RNA-binding proteins TDP-43 and FUS, which act as ‘couriers’ dropping off their RNA at the right part of the cell and then returning to the nucleus for the next package.
These binding proteins both play an important role in motor neurone health. In motor neurones affected by MND, the TDP-43 and FUS seem unable to make their way back to the nucleus so they form clumps in other parts of the neurone. How and why this happens is not really understood and several presentations on the first day of the Symposium provided insight into what might be going wrong. Dr Brian Dickie, Director of Research Development at the MND Association, summarises these presentations in his blog Libraries, Doormen and Harry Potter. You can also hear Brian talk about RNA proteins on the Symposium website.Read More »
The AMBRoSIA (A Multicentre Biomarker Resource Strategy In ALS) project is our biggest, most ambitious research undertaking to date. The project funding began in August, closely followed by being the focus of this month’s ‘Make Your Mark’ fundraising appeal. Here we explain more about what this flagship project is all about.Read More »
Although conventional brain magnetic resonance imaging (MRI) scans are often normal in people with MND, more sophisticated MRI techniques have shown changes in the structure of their brains as the disease progresses. A limitation of even the most recent MRI techniques is that they can only provide a snapshot of the brain at a single moment in the course of the illness.
Only a description of how these MRI changes evolve over time as the disease advances will tell us how the nerve cell damage due to MND is evolving, area by area, in relation to an individual’s symptoms. This could be obtained by collecting several MRI scans from the same person over time, but the nature of MND makes it challenging to get scans showing the course of disease over several years.
We are funding a three year PhD studentship that aims to use a new imaging method to define the progression of MND (our reference: 859-792). The researcher team, involving Profs Mara Cercignani and Nigel Leigh from the University of Sussex, will use MRI scans that have already been obtained from people with MND and healthy controls.Read More »
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
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 »
When diagnosing MND, it is important to look at the activity and impact of the motor neurones themselves – is the electrical message being carried down the nerve properly, and is it reaching the end of the nerve in the muscle? Malfunctions in the electrical activity at the muscle end of the nerve cell result in the muscle twitching that many people with MND experience.
One of the tests used to diagnose MND is an electromyography or EMG test. It involves putting needles into a muscle to measure electrical activity. It can be a painful and unpleasant experience, which doctors and patients are only willing to do when necessary.
There is evidence that ultrasound imaging may be able to detect the same malfunctions in the electrical activity of muscle as EMG, by looking at the way the muscle behaves when electrical activity occurs. Ultrasound images produce the typical grey scale images, for example pictures from baby scans, and can be used to provide images of any muscles in the body.Read More »