Closing the door on toxic proteins – new clues in understanding a genetic form of MND

The defects in the C9orf72 gene are known to cause motor neurone disease, but researchers don’t understand why. Defective copies of this gene are passed down in some families affected by the rare, inherited form of MND. This week MND Association grantees Drs Guillaume Hautbergue, Lydia Castelli and colleagues, based at the Sheffield Institute of Translational Neuroscience have published their research study providing some important clues about the toxicity of C9orf72. Their research is published in the prestigious journal Nature Communications. Continue reading

Dr Chris McDermott talks about his research at our Annual Conference

This year’s Annual Conference research talk was given by Dr Chris McDermott and focused on his research at the Sheffield Institute for Translational Neuroscience (SiTraN). His talk, adequately named ‘Improving the care and evidence base for symptomatic care’, was a very personal and informative talk to all that attended.

Dr McDermott gave a brief introduction about how he became a neurologist and got involved with MND research. He then talked about non-invasive ventilation (NIV) and how, through healthcare research, they have already gained evidence that NIV increases survival and improves the quality of life for people with MND. After this evidence was obtained, the technique gained National Institute of Health and Clinical Excellence (NICE) approval and NIV is now a standard treatment for people with MND who experience respiratory weakness.

Dr McDermott also mentioned how a ‘cough assist machine’ can be used to help patients cough and get rid of secretions and dirt. Information from the literature suggested a reduction of hospital admissions, and infections, in the year following the use of a cough assist machine for other diseases. The results from Dr McDermott’s MND Association funded study, looking at a cough assist machine for people with MND are yet to be analysed.

The rest of Dr McDermott’s talk focused on his current diaphragm pacing trial (known as DiPALS) being part-funded by the MND Association.

DiPALS

Dr McDermott explained that diaphragm pacing is designed so that people with MND do not have to be on long-term ventilation units, as the remote unit can be carried around when in use. Diaphragm pacing is similar to that of a ‘pace maker’, but instead of the heart it stimulates the diaphragm using an electrical current.

A video was shown of how the instrument’s electrodes are placed onto the diaphragm muscle during a 30 minute key-hole surgery procedure. The pacing unit is then controlled by an external remote at present, but if trials are successful an internal unit could be developed.

Dr McDermott stressed that the mechanisms in which diaphragm pacing acts is not known at present but suggested that it may cause stronger contractions or restore co-ordinated breathing.

An American study of 106 people with MND who had advanced respiratory problems previously found that 81% of trial participants were still alive after one year. Dr McDermott went on to explain that this study had no control group to test whether the diaphragm pacing unit improves life over and above that of current standards of care. However, the American study did find diaphragm pacing to be safe.

The DiPALS study in the UK has been recruiting patients with MND since November 2011 and compares NIV alone (control group) and NIV plus diaphragm pacing. Dr McDermott’s study aims to see if there is a difference in survival between the two groups, whether there is an improvement to quality of life, whether it is less intrusive, and whether the treatment is cost-effective. If diaphragm pacing does show a difference, then this could lead to NICE approval and become standard NHS-provided care in the UK. Dr McDermott went on to say that even if the study is found not to be a viable treatment the trial has already importantly shown that people with MND can have a general anaesthetic.

As the study is ongoing the final results are not available. Results are due in autumn 2014.

Overall, it was great to have an update into Dr McDermott’s research which stimulated an abundance of questions from all those that attended, leaving delegates with a real insight into some of the healthcare research funded by the Association.

More information

If you’re interested in attending a future MND Association conference to hear the latest about MND research, look out for our announcement of our 2013 Spring Conferences. Dates and locations will be announced on our website www.mndassociation.org.

Diaphragm pacing trial information sheet

AGM and Annual Conference summary on our website: http://www.mndassociation.org/news-and-events/events/conferences/AGM+and+Annual+Conference+2012

Research we fund

Match-making to find a new treatment for MND

Translating recent scientific discoveries in MND into the development of new and better treatments is a major challenge we face. To facilitate this process within the UK, we’ve recently played a role in match-making a key UK academic neuroscience department and a commercial organisation.

Pharmaceutical industry – the big, the small and the CROs

Discovery and development of a new medicine is always going to be expensive and never as rapid as everyone would like. Many major pharmaceutical companies cannot justify a large investment in a relatively rare disease like MND. They may not recover the costs even if a new drug is discovered. However, the landscape of pharmaceutical research has changed dramatically in recent years – the big multinationals are not the only players.

Smaller research companies, often termed ‘Biotechs’, have been responsible for many of the newer medicines discovered. They sometimes then collaborate with, or become a part of, a larger organisation to enable the development and commercialisation of the product. They can undertake research that larger companies, answerable to shareholders, consider too ‘risky’. The larger companies, facing decreased income as older medicines lose their patent protection, have been making cutbacks to their in-house research. However, they may be willing to take on a potential new medicine when evidence of its usefulness has already been generated.

Another group of companies, called ‘contract research organisations’ (CROs), will carry out part of the research process, typically under a contract from another company. This enables a large company to put extra people onto a project for a few months without having to employ them directly, which can be more flexible. Initially CROs undertook clinical research, testing new medicines on patients, but different CROs are now involved in all stages of the research and development process, often employing people with prior experience gained in the larger companies.

Universities

Drug discovery can also take place in University research departments. Industry has always taken advantage of the basic biological research done by academic researchers. Gradually, a few universities and institutes have become involved in other stages of drug discovery – facilitated recently by the willingness of scientists with key industry experience to move to academic roles. In the UK this has focussed on two areas: cancer (due largely to funding from Cancer Research UK) and ‘neglected diseases’ (usually diseases of the developing world, such as malaria).     

Forging a Partnership

The drug discovery CROs are now becoming interested in partnering with academic researchers, to facilitate their drug discovery. My personal industrial experience means that I know people in some of these CROs, and they know of my move to the MND Association. One particular company, Peakdale Molecular became aware of the research underway at the Sheffield Institute for Translational Neuroscience (SITraN), and were particularly keen to know more as they are based relatively close. We encouraged some of Peakdale’s scientists to join us at the recent one-day conference in Liverpool, where they heard Dr Ramesh from SITraN give a presentation about his Association-funded project to test potential drug compounds in his zebrafish model of MND. The following week I travelled north again – South Yorkshire this time – to attend the first meeting between representatives of Peakdale and some of the scientists at SITraN. 

We heard about several projects, mostly MND-related, but also one on Parkinson’s disease, and we were shown around the SITraN labs. The Peakdale managers described the ways they would be able to help an academic team, for example, to select and source compounds for testing in the various biological assays at SITraN.  They were impressed with the results shown for the various projects, and could readily see how the experience and expertise of their staff might help the academic projects. Finally – and key news for the academics – Peakdale announced they would like to start by providing some help without charge, although purchase of compounds from commercial suppliers will inevitably incur costs.

It’s only a few weeks since that first meeting in March 2012, but already a Confidentiality Disclosure Agreement has been put in place to allow the start of collaborative working between Peakdale and SITraN scientists.  Such an agreement is important if any discoveries are later considered to require protection by patent filings. 

We really hope they do, as that will be one small step forward in the search for a new treatment for MND.

Very recent update: SITraN scientists have placed an order for a test compound to be synthesised by Peakdale for their MND studies and a second meeting has taken place between SITraN scientists and the Peakdale Chemists to further forge the working partnership on a number of projects.