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.


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.

Come fly with me

The Fly
The Fly. Courtesy of MND Association funded researcher Dr Frank Hirth, based at King’s College London

Although millions of years of evolution separate humans from insects, a tiny fruit fly called Drosophila melanogaster has been one of the most extensively studied organisms for more than a century, leading to many advances in research. But why are flies so useful? And can we really learn anything from them?

Why fly?

It is easy to see that this fly has advantages in the laboratory. They are very small and easy to keep, but still large enough to study in detail with relatively simple microscopes. They breed easily from 10 days old, producing many genetically identical offspring from each mating. This makes it easy to study several generations over a matter of weeks.

Simple yet sophisticated

Although considered a simple species, the fly is actually quite sophisticated, with structures that are equivalent to organs such as the heart, kidneys and gut.  The brain and nervous system are considered particularly complex, making the fly valuable for the study of neurodegenerative diseases.

Genetically the fruit fly is also much simpler than a human – it has approximately half the number of genes that we do. But it’s not the number of genes you have that counts; it’s what you do with them!

Luckily, about three-quarters of the genes implicated in human disease have a related gene in the fly, with a high level of similarity between the two. Many methods and techniques have been developed, so researchers can switch the fly’s genes on and off at various points in its life-cycle, or in different parts of the body, and then observe the consequences.

MND fly research

Between 2004 and 2009, only about four scientific papers per year described studies using these fruit flies for MND research. In conjunction with the recent upsurge in genetic discoveries related to MND, there has been a rapid increase to twelve publications in 2010, and a further seven already in 2011.

The MND Association is a leader in funding and promoting cutting edge research and we are currently funding two PhD studentships making extensive use of the fruit fly. You can find out more about these projects on our website:

Understanding disease mechanisms of MND in the fruit fly

How does faulty TDP-43 affect MND in fruit flies?

Learning to fly toward drug discovery

There is considerable interest in using the fly to test potential drugs for MND, as there has been some success in this approach in other conditions.  Like the zebrafish model many more substances can be tested than would be possible with a mouse model, and the results may tell scientists more than a cell-based screen. However, this is not yet a routine approach to drug discovery – historically fruit flies have not been used in this way by pharmaceutical companies. It remains to be seen whether any promising compounds identified using fly models will actually progress to being drugs for the treatment of human diseases.

For such an approach to be useful for MND, there needs to be a reliable and relevant fly model. Recently published work has been focussed on exploring the role of proteins known to be involved in MND such as TDP-43 and FUS. When they publish their work, researchers often hint that their models will be useful in the development of new treatments, even if this was not their main aim.

The use of the fly to discover new medicines may still be some way off, but we can be sure that the tiny fruit fly is already contributing to research in a very big way.

One week on – Reflections on my first experience of the International Symposium on ALS/MND

Our recent blog articles describe lots of fascinating science and the progress in the care and treatment of MND/ALS that was presented at the symposium.  Personally, another really positive aspect was the opportunity to meet some of the researchers face-to-face. This included several senior scientists and clinicians whose work we support, some of whom gave lectures or chaired sessions. The symposium also gave presentation opportunities to PhD students and post-doctoral scientists, some of whom were attending their first International Symposium. We invited several from the UK to an ‘ice-breaker’ social on the Friday evening before the main lecture sessions began. Not all were able to attend, but a good group gathered with us, getting to know each other, and we met others later as they presented their posters. 

Sheffield University was well represented, including current grantees Emily Goodall and Clare Wood-Allum who both presented posters. Newer to ALS research was Guiseppe (‘Bepe’) Battaglia part of a cross-disciplinary group of collaborators who call themselves ViNCeNS for ‘Virus-like Nanoparticles for targeting the Central Nervous System’ with a website at

‘Fishing’ for new animal models of MND

Two others at our ‘ice-breaker’ gave lectures during the Saturday session on ‘Emerging Disease Models’.   Marc Da Costa (also from Sheffield) described some outcomes of his PhD project developing a new zebrafish with a mutated SOD1 gene.  Zebrafish are popular models for neurological conditions (there was a second presentation from an US-based group), as the fish embryos are transparent, so their neurones can be studied easily under the microscope.  Their muscular strength can be judged by the amount they move (studied by automated analysis of video) or by their progress swimming against a ‘current’ in a tube.  Marc studies the differences between fish with normal or mutant SOD1.  The latter have more difficulty swimming, and are more vulnerable to stress (for example, added toxic chemicals).  Marc can test the effects of potential drugs on the stressed fish, and has already seen some promising results.

Looking in a ‘library’ for MND mice

Another new animal model was presented by Peter Joyce (MND Association funded, based at the Medical Research Council Laboratories near Oxford).  His mouse strain carries a mutation (mistake) in its native (mouse) SOD1 gene, matching one recently reported from a human family with ALS.  This is different from the more established SOD1 mouse model, in which the MND-like symptoms develop as a result of multiple copies of an added human mutant gene.  Peter is studying the timescale in which muscle problems develop, relating these to changes in the neurones.  The MRC has a huge ‘library’ of mouse mutations available, so Peter will be investigating if others match mutations reported in different ALS families, possibly looking for collaborators to work on these.

Presenting the impact of healthcare decisions

A completely different type of research was presented as posters by two researchers working with Carolyn Young at the University of Liverpool.  Hikari Ando has been studying the reasons why some people with MND decide not to accept the offer of non-invasive ventilation (NIV), and the extent to it is actually used by at home.  Chris Gibbons’ work covered the assessment of quality of life for people with MND, particularly the role of fatigue and depression. 

Final thoughts

It was particularly inspiring to meet so many UK-based researchers, filling all of us from the MND Association with more incurable optimism.  Of course we also met many other people too – the attendees, many of whom collaborate internationally, came from more than 30 countries.

Inspired by viruses

I attended a fantastic talk this morning in the session on ‘Translational Strategies’. This session is all about moving laboratory ideas for new treatments for MND into the clinic to test them in clinical trials.

The first talk was given by Battaglia, based at the University of Sheffield. In this presentation, he described a multidisciplinary project to develop synthetic ‘nanoparticles’ which could be used to deliver future therapies to the brain and spinal cord – and even eventually into motor neurones and support cells. This project really does take collaboration to a new level by combining the expertise of physicists, chemists and biologists and taking inspiration from the ways in which viruses have evolved to get into our cells.

In the second presentation, we heard how a small company in California (iPierian) are taking cells from patients with ALS and developing them into stem cell-like cells called ‘induced pleuripotent stem cells and then turning them into motor neurones. Their next aim is to test new compounds on these cells to test for their effectiveness in a human cellular model of MND in the hunt for new and better treatments for MND.

Record breaking number of summary applications received

As posted recently, we are just starting our next research grant application round – and the number of summary applications received broke the record set a year ago.

We received 26 applications – 5 for PhD studentships and 21 for projects (requiring more experienced scientists).  These cover a wide range of areas, including genetics and cell-based research building on recent discoveries, further development of animal models, and the search for potential new treatments for MND. 

Only one application didn’t fit our criteria, so the remaining 25 will each be reviewed by three members of our Biomedical Research Advisory Panel (BRAP).  This left Natasha very busy last week sending out packs of summaries to BRAP members, as well as logging all the applications on our IT systems, and acknowledging their receipt to the applicants. 

When all the reviews are returned later this month, the reviewers’ scores will be used to determine which applicants are asked to submit full research proposals.

We’ll keep you updated on the progress of our research funding grants round – in the meantime, if you’re interested in finding out more about our current portfolio of research projects then please visit our ‘research we fund’ section of our website.

‘Hello’ from the newest member of the team

As the newest recruit to the Research Development Team, I have been asked to let everyone know a bit more about me.  Previously I was a Medicinal Chemist working for GlaxoSmithKline (GSK) for almost 20 years.  In that time I “survived” two corporate mergers and worked at three different research sites.  For almost a third of my career I was involved with neuroscience projects, seeking new therapies for Alzheimer’s Disease or chronic pain.  My main role was to design and synthesise new molecules, which were then passed to biologists for testing, the results being used for the next round of design.

Earlier this year, GSK senior management decided to decrease its neuroscience research, resulting in many redundancies.  I have extensive voluntary experience of working with disabled people, and in organising other volunteers.  I decided to see if I could use my scientific knowledge in a job which would benefit sick or disabled people – and then I saw the advert for Research Grants Manager at the MND Association.  As I discovered more about the disease and the Association (thanks to all involved with the invaluable and comprehensive website), met enthusiastic people at my interview, and recognised that I had previously known people with MND though my volunteering, I realised this would be a great opportunity.

With little prior knowledge of Motor Neurone Disease, I have been on a steep learning curve over the past two weeks.  I have had meetings with representatives from many of the other teams, so I can understand how we all work together for the common aims of the Association.  I was lucky to attend the AGM and Annual Conference, where I met an even greater range of people, including volunteers and some of the Trustees.  The keynote speaker was Professor Nigel Leigh (Kings College, London), who gave an excellent overview of the current status of biomedical research into the causes of MND.   It is important that I have a good understanding of the relevant science before the Biomedical Research Advisory Panel Meeting in October, so I have been reading lots about recent and current research.  It has been quite hard work to understand the detailed biology, especially getting to grips with all the acronyms , but my colleagues have been answering my questions with patience.  I have also accompanied Brian to a meeting arranged to foster collaboration between two different groups of researchers.

My experience in “drug discovery” falls somewhere between the main areas of research currently funded by the MND Association – ie the biomedical studies into causes of the disease and the clinical investigations of potential therapies and of ways to improve quality of life for patients.   However, my industrial experience has given me a good understanding of how basic research is essential before new therapies can be developed.  Already we are funding one research project in collaboration with a biotech company and another where the academic scientists hope to identify chemicals that can correct a problem with faulty SOD1 proteins.  With “incurable optimism” we can look forward to more projects like these in the future.