Clinical trials update from Symposium

Clinical trials determine if potential treatments are safe and aim to prove beyond reasonable doubt whether a drug is beneficial. They are therefore the gold standard of treatment research.

More information on the different types of clinical trial can be found on our website and in our information sheet on the topic.

This year the Symposium session on clinical trials looked at three drugs and one therapy. Dr Brian Dickie has posted a separate blog on one of these drug treatments – Edaravone.

A summary of the results from the drugs and treatments discussed is below. More information on each of them in detail is later on in this blog.

Ibudilast: This drug was safe and well tolerated in those who were not using non-invasive ventilation. However, these are results from an early stage trial so more research is needed to establish possible long-term benefit.

Methylcobalamin (Vitamin B12 injections): If this treatment is given early (within 12 months of diagnosis) then it showed an effect at increasing survival in a small sub-group of those taking part in the trial. This effect was not seen when the treatment was given further on from diagnosis.

Stem cell therapy: This small, early Phase 1/2 trial was testing the safety of bone-marrow derived stem cell injections into the spinal cord. The researchers found this treatment had no major side effects. Further studies are needed to evaluate the effectiveness and safety of this treatment over the long-term.Clinical trial flow chart

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Edaravone trial presentation sparks interest

Bar a few bacteria usually found hitching a ride on our dental plaque and digestive system, every living cell in the human body needs oxygen. Some cells need more oxygen that others, dependent on much energy they need to produce to function. Neurones are particularly active cells (the brain uses a fifth of all the oxygen consumed by the human body) and motor neurons are amongst the most energy hungry of all.

Unfortunately, the process of producing cellular energy isn’t 100% efficient: a small but constant amount of waste products called free radicals (yep, those things that the beauty product industry bangs on about) can build up in the cells. If not kept in check, they can start to wreak havoc within the cell.

Our cells have quite effective ways of dealing with free radicals, but these ‘cellular defences’ become less and less efficient with age. As we age, our energy production processes lose efficiency, causing a ‘double-whammy’ of not only more free radicals being produced, but also less effective ways of dealing with them. When neurones are damaged, as happens with neurodegenerative diseases, then everything gets exacerbated even further, leading to a vicious cycle of events. Continue reading

Choices around invasive ventilation

Mechanical ventilation for people with motor neurone disease (MND) is a sensitive and little discussed topic. Yesterday’s respiratory management session of the International Symposium on ALS/ MND began with several interesting and thought provoking presentations on the subject. Pia Dryer from Aarhus University Hospital in Denmark presented the results of a review of their respiratory service over 17 years, including a discussion of invasive ventilation. Dr Mike Davies is a respiratory consultant at the Papworth Hospital in Cambridge in the UK, where he and his colleagues run a weaning service supporting people to come off invasive ventilation.

Choosing ventilation, or not

Summary of respiratory choices in Denmark

Summary of respiratory choices of people with MND in Denmark

Over 400 people with MND had been treated at the Home Mechanical Ventilation service since its inception in 1998, Pia Dryer explained at the beginning of her talk. During the discussions in clinic people had the choice about the options available for managing their breathing symptoms, some chose no ventilation, others non-invasive ventilation (NIV). From NIV some then progressed to invasive ventilation or tracheostomy, and finally some chose to go straight to invasive ventilation. People with MND had the choice of all of these options, 90 of them chose either NIV and then invasive ventilation or invasive ventilation first without NIV. The talk was really brought to life by showing clips of Birger Bergman Jeppesens the star of a number of films on YouTube. He was the first patient to ask for invasive ventilation at the Aarhus clinic. Dr Dreyer went on to talk about the legal and ethical aspects of withdrawing ventilation from people with MND at the end of life, a topic that was discussed in more depth later in the session. Continue reading

Respiratory support: the big debate on Symposium day 2

Different ways to support breathing were the main focus of the second clinical session on day two of the Symposium. Researchers from two MND Association funded studies presented their work looking at diaphragm pacing and also the withdrawal of ventilation support.

Lungs - Symp session pictureDiaphragm pacing

The NeuRx diaphragm pacing system (DPS) is a device developed to aid breathing by stimulating the large muscle that helps you to breathe – the diaphragm.

In 2011, the Food and Drug Agency (FDA) in the USA approved NeurRx DPS as a treatment for respiratory failure in motor neurone disease (MND). The treatment was not required to go through the series of clinical trials that is needed for a new drug. The FDA approved it on the basis of one small study because at the time the probable benefit to health outweighed the risk of using it.

Due to this lack of clinical evidence, this prompted further research in the USA and Europe to test its effectiveness on symptom management and survival. Continue reading

Our wheelchair project – helping people with MND around the world

Karen Pearce, the MND Association’s Director of Care, blogs about presenting the Association’s wheelchair project at the Allied Professionals Forum, which happened prior to the International Symposium on ALS/MND.

Karen PearceAt the Allied Professionals Forum I had the opportunity to present our wheelchair project, particularly looking at anticipating future needs and the powered neuro wheelchair. The presentation seemed to go well, however there were no questions at the end. In my mind this could mean a few things, either what I had said wasn’t interesting, or it wasn’t relevant or maybe I had covered everything people wanted to know. This felt unlikely to me.

 

Thankfully after the presentation a few people approached me, a couple to ask for our evidence so they could influence the people who provided powered wheelchairs in their country. Another person asked about how a feature of the powered neuro wheelchair could possibly be used if the wheelchair was tilted back. Fortunately she uses wheelchairs from one of the manufacturers we work with. Following my talk she is going to ask them for a demonstration model for her to try – a fantastic example of sharing work that will now hopefully support across many countries. Continue reading

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. Continue reading

“To test or not to test”, that is the question

A huge ‘atlas’ mapping the locations of motor neurone disease (MND) causing mutations within the genetic code has been collated. This has followed years of genetic analysis and sequencing of the DNA of people with MND, and their family members.

The people who have given their time and DNA have played a hugely important part in helping researchers learn more about MND, particularly the inherited form of the disease. Dr Benatar, who spoke in this session highlighted “there is a desire and interest by people who may have inherited MND to contribute to research into this disease, if not for their benefit then for the benefit to future generations of their family“.

The first session on day two of the Symposium looked at the topic of genetic testing and counselling. All the presentations had a common theme of this topic being a two-way street – after all the help people with MND and their families have given to help with research, now research efforts have been focussing on the ways to better help those who decide to have genetic testing for inherited/familial MND. Continue reading

New ALS gene represents another small step

It wouldn’t be the Symposium without a new gene discovery.

Although technology has allowed incredible advances in the gene-hunting field, this is countered by the fact that as more and more familial amyotrophic lateral sclerosis (FALS) genes are found, it makes the search for the remaining unknown genes harder  This is in part due to the fact that the undiscovered genes are likely to be increasingly rare (so even more rigorous detective work is needed) but the challenge is compounded by the fact that there are fewer and fewer samples with an unknown cause available each time a new gene is found.

The solution to these problems lies with greater collaboration, sharing knowledge, expertise and of course the vital samples needed for the research to happen.Dr Brad Smith

Dr Brad Smith (King’s College London) unveiled the latest collaborative effort, involving over 50 researchers across 9 countries. The researchers took an approach called Exome Sequencing, which analyses the 1% of the genetic code where most mutations are likely to be found, to look for genes in several hundred FALS cases where the genetic cause was still unknown. They then compared their findings with those from 60,000 individuals in publicly available databases. Continue reading

Spreading the seeds of an idea: MND disease pathology

With motor neurone disease (MND), the muscle weakness almost always starts in a single part of the body, with the weakness then spreading to other muscles in an orderly fashion. Neurologists are usually quite good at predicting which muscles will be affected next, slightly less so at predicting when this will happen.

The physical changes on the outside will be reflecting events occurring in the ‘closed box’ that is the brain and spinal cord. The latest imaging techniques are starting to give us more of a picture of what’s happening in the central nervous system as the disease progresses, but further technological advances will still need to be made. The clearest picture still comes from the study of generously donated and incredibly valuable post-mortem tissue.

The second day of the Symposium saw researchers present in the Clinical-Pathological Correlates of Disease Progression session, focussing on how to understand disease progression, the role of prions in neurodegenerative diseases and the relationship between MND and frontotemporal dementia. Continue reading

Improving the classification of ALS – can we make it logical?

Yesterday at the International Symposium on ALS/MND Prof Ammar Al-Chalabi (Director of King’s Care Centre and Professor of Complex Genetics at King’s College London) cautioned the motor neurone disease (MND) research community about the confusing way we describe this disease we are all fighting. He started his talk by showing a standard definition of what MND is, and then pointed out some of the areas that were inconsistent – or has he put it, illogical.

For example is MND described by: whether it affects the motor neurones running from the brain to the spinal cord (upper motor neurones) or from the spinal cord to the muscles – whether that’s in our hands, arms or feet (lower motor neurones)? Or is it defined by where the symptoms appear – in what Prof Al-Chalabi described as the geography – either with speech and swallowing problems, or foot drop, or clumsiness / loss of dexterity in the hand?

Asking the Dr Spock question..

To illustrate his point he shared the results of a survey he’d carried out with over 100 neurologists across Europe, North America and Australia. Firstly he asked them what terms they used to give definitions of MND, ranging from amyotrophic lateral sclerosis (ALS), primary lateral sclerosis (PLS) and progressive muscular atrophy (PMA) to ‘classical’ MND – from a list of 26 descriptions, all of them were used! Continue reading