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 →
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.
Study design and biological and phenotypic heterogeneity
Therapeutic / Symptomatic interventions in clinical trials
Patient recruitment and retention
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.
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 →
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 (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 →
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 →
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.
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 →
The fantastic news that Patrick Joyce and his co-inventors have won the 2015 Hackaday Prize for their ‘Eyedrivomatic’ invention is one of a number of research prizes announced this autumn.
Prof Martin Turner receiving his award from Prof Jane Dacre, RCP President
At the beginning of November Prof Martin Turner was presented with the Graham Bull Prize for Clinical Science by the Royal College of Physicians (RCP). The Prize is awarded to a member of the RCP under the age of 45 who has made a major contribution to clinical science.
The winner of the Graham Bull Prize is also invited to deliver the prestigious Goulstonian Lecture, an annual lecture given by a young RCP member that dates back to 1635 and the list of previous speakers reads as a ‘Who’s Who’ of the history of British Medicine!
Those of you who know Martin, in particular the many participants who volunteer for his BioMOx research programme will be pleased to see his new title: he was awarded the title of Professor by the University of Oxford in July this year. Aren’t Professors getting younger looking these days…! Continue reading →
Under the leadership of Dr Christopher McDermott, based at the Sheffield Institute for Translational Neuroscience (SITraN), research published today on 29 May 2015 in the Lancet Neurology highlights that better weight management in MND is key to survival.
Following on from initial results presented at the 25th International Symposium on ALS/MND in December 2014, the Prospective Gastrostomy (ProGas) study in MND aimed to investigate the optimal timing for gastrostomy in MND due to the lack of evidence available.
Dr Chris McDermott (Sheffield Institute for Translational Neuroscience, University of Sheffield)
The MND Association’s Director of Research, Brian Dickie explains more about ‘GM6’, also known as ‘GM604’, a drug in development by an American pharmaceutical company Genervon.
The Association funds a wide range of research that leads to new understanding and treatments, which may one day, bring us closer to a cure for MND. We are hopeful that the increasing international research effort into the disease will accelerate the development of an effective treatment for MND. However for non scientists I also fully appreciate how the ‘system’ often seems designed to impede rather than assist this process.
There has been much discussion online about the results of a small scale study of a drug called GM604, or GM6, produced by the American pharmaceutical company Genervon. You can read some general comments about the drug on our website. I’ve written this blog to explain in a little more detail why the research community is cautious about the results. Continue reading →
Published on 19 February 2015 in the Journal Science,an international team of scientists have found mutations in the gene TBK1 as a contributory risk factor in MND.
The majority of cases of MND are caused by a combination of subtle genetic, environmental and lifestyle factors. These subtle genetic factors in the majority of cases of MND (sometimes known as susceptibility genes) may increase someone’s risk of developing MND, but they do not solely cause the disease (they must be present in combination with a number of other factors in order to tip the balance for someone to develop MND). Find out more here.
Under the leadership of Dr Goldstein, based at Columbia University, the researchers have identified a new MND susceptibility gene – TBK1. The researchers used whole genome sequencing to sequence the entire DNA of over 2,874 MND samples in America – you can find out more about this technique here. By screening a large number of samples, the researchers identified mutations in the TBK1 gene as a common subtle genetic factor involved in some cases of MND in America. Continue reading →