Commitment to COMMENDable research

Whilst the vast majority of MND research happens in the lab, there is also an increasing amount of research activity looking into how best to manage the various symptoms of the disease.  There are a lot of unanswered questions as to ‘What Works and What Doesn’t?’ and without a decent level of evidence, it is increasingly difficult in these cash-strapped days to get new or even existing types of therapy adopted into mainstream statutory care.

One such ‘Cinderella’ subject is psychological support for people with MND. It’s hardly surprising that studies show almost half of people diagnosed with MND experience depression and almost a third experience anxiety, yet there is very little guidance on how to best address these symptoms. As a result, formal psychological support is not routinely offered and where it is, the particular approach taken is based on best judgement rather than robust evidence.

NIHR-logoSo, it was encouraging news when last year the research funding arm of the NHS, the National Institute for Health Research (NIHR), announced a call specifically for projects to look into the ‘Clinical impact and cost-effectiveness of interventions to improve the psychological health of people with MND’.  The result of that funding call is a major new therapy research trial, led by Dr Rebecca Gould of University College London and Professor Christopher McDermott of University of Sheffield, that will start in December 2017.

“Psychological distress is such a poorly-recognised and investigated aspect of MND, not only for the patient but also of course for their carers and families” says Dr Gould.

“Needless to say, it can have a profound effect on quality of life, but some studies also indicate that it may also be linked with reduced survival.

“We were delighted that the MND Association was keen to support the proposal, not only by lending their expertise, but also by offering to contribute up to £80,000 to help support the therapy costs, which are not covered by the £1.3 million NIHR award.”

The COMMEND study (Acceptance and Commitment therapy for people with motor neuron disease) will focus on a particular technique known as Acceptance and Commitment Therapy (ACT), which has been shown to be beneficial in chronic pain and other chronic physical and mental conditions.

Dr Gould and her colleagues have divided the study into two parts; the first part, taking up to 19 months, will focus on developing an ACT intervention that is specifically tailored to the needs of people with MND. This will occur through a series of workshops and interviews with people with MND, carers and healthcare professionals. Once the intervention has been developed, a small number of volunteers will be recruited to check the ease of use and appropriateness of the therapy. Once they are confident they have the ‘right tools for the job’, the researchers will conduct a randomised trial (run in a similar fashion to a drug trial) in almost 200 people with MND to find out whether ACT can improve psychological health and quality of life. The trial will consist of up to eight face-to-face sessions held at the participant’s home or in GP surgeries (videoconferencing sessions will also be offered where necessary). Carers will also be asked to complete some short questionnaires to check whether there are any knock-on effects on their quality of life. The study is set to initiate later this year, with recruitment for the workshops due to start in December 2017. Recruitment for the first part of the study aimed at checking the ease of use and appropriateness of the therapy is expected to run from June 2018, and the randomised trial from July 2019.

“We were thrilled by the enthusiastic response when we first raised this study with colleagues in MND centres across the country. We hope that at least 14 of the Association’s Care Centres will be able to take part in the main trial in due course.

“Ultimately, we hope to demonstrate that ACT has a positive and cost-effective impact for people with MND, which would provide the evidence base that will support the roll-out of the intervention across the NHS – and perhaps in other countries as well.”

 

Lithium revisited: Is there a baby in the bathwater?

At last year’s Airlie House workshop to develop new ALS/MND Clinical Trial Guidelines the focus was, of course, on MND, but there was also important input and learning from outside the field.

One of the most fascinating presentations was from an oncologist who was explaining how detailed genetic analysis of tumours was leading to an understanding of why some experimental cancer drugs appeared to only work in a small subgroup of patients. The take home message from the cancer field was that there should be more effort made in future MND trials to identify and analyse smaller subgroups of patients, in case a potentially positive effect might be missed.

A new research paper, published in the journal Neurology, raises some intriguing findings from the trials of the drug lithium that were carried out several years ago. Lithium generated a lot of excitement when researchers in Italy reported a positive effect of the drug in the SOD1 mouse model of MND. Almost as an afterthought, their research paper mentioned that they had tested the drug in a small short-term trial in patients and it appeared to have some effect. Continue reading

IPG Prize recognises young research talent

I firmly believe that the quality of research is only as good as the researcher doing it, which is why the MND Association places a lot of emphasis on providing opportunities to attract, train and retain the brightest and best investigators in the UK and Ireland to develop their careers in MND research. These range from our ‘entry level’ PhD Studentships through to our successful Clinical Fellowships (funded jointly with MRC) and our more recent Non-Clinical Fellowship programme, offering opportunities to outstanding young researchers at a variety of career stages.

It’s also one of the reasons why the Paulo Gontijo International Medicine prize, presented at the Symposium Opening Session, is always an early highlight for me. Continue reading

New fellowship to investigate muscle fasciculations

During Awareness month in June we reported on the work of Dr James Bashford at King’s College London, exploring new ways of measuring muscle fasciculations in people with MND. The results from the one year pilot study have shown a lot of promise, which has led to Dr Bashford recently being awarded a Clinical Research Training Fellowship.

A common symptom of MND is the ‘rippling’ of muscle under the skin, these are known as muscle fasciculations. Continue reading

Could a Diabetes drug be useful in treating MND?

Today we announce a new collaboration for a preclinical research study on the diabetes drug liraglutide, in the hope that positive results will lead to a clinical trial in MND. Here’s a little more about the rationale behind the study.

The idea that drugs licensed for one disease may have some use in another completely different disease is not new, but it has gained much more attention in recent years. Researchers are developing a new understanding of disease processes, leading to new ‘drug repurposing’ opportunities, with the additional potential to reduce the time and cost of drug development.

Significant advances in genetics and molecular biology in recent years have greatly increased our understanding of the pivotal, carefully balanced cellular processes that usually keep motor neurons healthy but, when disrupted, can cause a cascade of degeneration leading ultimately to their death. Continue reading

ALS/MND Clinical Trial Guidelines: your opportunity to comment!

A few months ago we wrote an article about the ALS Clinical Trials Workshop which took place in Virginia, USA. Since then the Guidelines Working Groups have been busy turning the large number of issues debated into a first draft of a new set of guidelines. This is open for comment from 1- 31 August.

The guidelines will be posted on this website, and comments can be sent to guidelines.public.comments@gmail.com.

The guidelines are divided into sections:

  • Preclinical studies
  • Study design and biological and phenotypic heterogeneity
  • Outcome measures
  • Therapeutic / Symptomatic interventions in clinical trials
  • Patient recruitment and retention
  • Biomarkers
  • Different trial phases and beyond – (there are two sections on this)

Within each of these sections, there are many recommendations. The Clinical Trials Guidelines Investigators want to ensure that all interested people and stakeholders have an opportunity to provide input – whether you are a researcher, clinician or person with MND.

Thank you very much for your help.

For more information, please see a copy of their press release below: Continue reading

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

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

The BMAA story in a nutshell

Research into the neurodegenerative condition known as Guam ALS-Parkinson Dementia Complex (ALS-PDC) has tended to find itself slightly isolated from the mainstream MND/ALS research world (‘isolated’ being a good word given that the location of the island itself) but I’ve had an interest since I was first introduced to the subject as a PhD student a quarter of a century ago.

This topic was raised once again on day one of the International Symposium on ALS/MND.

Guam map

So where exactly is Guam?

The Guam Story…

For those of you not familiar with this fascinating and convoluted story, the science writer Wendee Holtcamp has written an excellent article on the subject but in a nutshell (an ‘in joke’ for those who know the Guam story) the basis of the hypothesis is that a toxic molecule called BMAA (beta Methylamino-L-alanine) is produced by certain forms of blue-green algae. The theory goes that the residents of Guam for a while were exposed to higher than usual levels through their diet, which led to a high incidence of ALS-PDC on Guam in the 1950s and 1960s. Continue reading