Motor neurone disease affects around 2 in every 100,000 people each year in the UK.
 
 
Motor neurone disease affects around 2 in every 100,000 people each year in the UK.

Science is expensive

Dr. Katie Sidle talks to Professor Peter Thomas about her work in understanding motor neurone disease.


Peter Thomas

Peter Thomas

Professor Peter Thomas is COO of the Leasing Foundation, Director the Manifesto Group and Creative Director of Medicine Unboxed.
Peter Thomas

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Introduction from Executive Producer JO DAVIS

Motor neurone disease affects around 2 in every 100,000 people each year in the UK. There are about 5,000 people living with the condition at any one time. Sufferers and their carers find the condition frustrating, challenging and sometimes terrifying. Motor neurone disease affects around 2 in every 100,000 people each year in the UK. There are about 5,000 people living with the condition at any one time. Sufferers and their carers find the condition frustrating, challenging and sometimes terrifying. Peter Thomas talks to Dr. Katie Sidle, world-leading motor neurone disease researcher.

Who should be interested in this? Anyone interested in philanthropy and scientific and medical research.

 

“To be faced with patients who are dying with their loved ones sitting next to them – there’s nothing more motivating for my research.”

– Dr. Katie Sidle, University College London Hospitals

Dr Katie SIdle

Dr Katie SIdle

“We used to think that motor neurone disease was a condition that just affects the nerves responsible for movement. But it’s also clear that it affects peoples’ thinking. Motor neurone disease patients are particularly easy going and likeable patients, and sometimes it’s because the disease is also probably targeting the parts of the brain that are responsible for personality.”

I’m 20 minutes or so into a conversation with world-leading motor neurone disease (MND) researcher and clinician Dr. Katie Sidle when she tells me this. Having read about the disease and its progression in preparation for talking to Katie, I’m completely taken by surprise. It’s not something I had come across before. “The problem is”, says Katie, “that patients sometimes don’t recognise their own need to get treatment and do less well as a result”.

It’s not the last time Katie is going to surprise me over the course of our hour-long discussion over a crackly Skype connection between Melbourne and London.

The reason I’m talking to Katie is to catch up on her work, a year on from her talk at the Leasing Foundation Christmas Lunch in 2012, about progress in understanding how the disease works and how to treat it.

To be faced with patients who are dying with their loved ones sitting next to them – there’s nothing more motivating for my research.

Katie is a consultant neurologist, Co-Director of the NHNN MND Association Regional Care and Research Centre and is responsible for the care of patients in MND in her clinic at University College London Hospitals. Her scientific background was in researching the neurodegenerative disease CJD (Creutzfeldt–Jakob disease). Her understanding of how CJD worked led her to her current research in MND.

“Our research is going extremely well”, says Katie. “ We’ve developed a method of using brain and spinal cord tissue from patients who died of MND, extracting the protein we think is the cause and then layering it on cells so that we reproduce the disease state. This is a breakthrough because it starts to confirm our belief that these rogue proteins are responsible. We’ve been using kidney cells to do this, and the next step is to use brain cells that we grow from stem cells. I’m excited because we’ve done this in three years and this something that would often take much longer.”

I’m excited because we’ve done this in three years and this is something that would often take much longer.

What I did understand from my reading is that MND – also known as ALS or Lou Gehrig’s disease – is the result of a combination of genetics, environmental and lifestyle factors. One of these, as suggested in a variety of research studies, is that exercise may increase the risk of MND. How do these factors work together in the disease, I ask?

“The best parallel is that of cancer”, she says. “Some people get cancer at a very young age because they have inherited specific genes. But there are also environmental factors that can affect cancer – smoking for example – and if you happen to have the genes and you are a smoker, you are more likely to get cancer. It’s the same for MND. Most cases occur out of the blue. There’s nothing someone has done – it’s just that their genetics have predisposed them. Some patients have more of a tendency to develop MND, and if they are exposed to certain environmental factors it can mean they get the disease at an earlier age. One of those factors is excessive exercise, and so in the clinic we do see younger patients who have a history of excessive exercise. We’ve had long-distance runners, weightlifters, gym instructors. The belief is that because these people are constantly damaging their muscles it sets off an unstoppable cascade of proteins that results in getting the disease a decade earlier than they would have done. Exercise isn’t in its own right the cause of the disease.”

Finding the rest of the genes that cause of MND is a big challenge at the moment.

If there is a predisposition, can people be tested for it?

“Only in about 5% of cases do we find that there a family history of this disease” says Katie. “And even in those families where we know there is a family history, we only know about 30-40% of the genes responsible for causing MND. So even if we tested you for those, it still wouldn’t mean we could say whether you would get MND. Finding the rest of the genes that cause of MND is a big challenge at the moment. For the last 50 years or so we’ve been focusing on one gene, but in the last 8 years we’ve identified another four genes – one of them found by our team at UCL.”

I tell Katie that I’m interested in what kinds of technology is used in the science of understanding the disease. Technology such as gene sequencing is now advanced, but what other kinds of technologies are important in Katie’s work?

“Gene sequencing has shown exponential improvement. The first estimate of the time needed sequencing the human genome was 10,000 years. Now sequencing someone’s genes is routine. That’s what’s allowed us to find the new genes responsible for MND, and I have no doubt that in the next 5 years we will find all the other genes. The other very exciting area of technology is imaging, where we now have the ability to see the pathways of cells and how those cells travel in the brain. In the next few years we’ll be able to image people’s brains and look at individual molecules. That will give us a way of understanding the progression of the disease and how effective new treatments are.”

I’m hopeful that in the next 20 years we will have an effective treatment for this disorder.

Despite all the advances there are frustrations. The frustration of seeing patients who suffer from the disease, and eventually die because of it, is what drives Katie’s work.

“Right now there are no effective treatments” she flatly states. “There is only one drug that is licenced and that will slow the condition down by about three months. But given that by the time most patients are diagnosed they only have 14 months to live, three months can be a long time.”

“It’s also frustrating because we have probably been looking at this disease in the wrong way for the last 50 years. Research has focused on a very rare subset of MND, not the bulk of the disease. Now we understand the role of this protein [called TDP43] we can understand what drugs can be used to target it. It’s important that we now try to understand the exact way this protein works in the brain and spinal cord. We know that the protein becomes rogue and accumulates. But is this causing MND due to a ‘loss of function’ – the protein can no longer do the job it should – or is it due to the protein becoming toxic? As we understand exactly how this works we can develop therapies. I’m hopeful that in the next 20 years we will have an effective treatment for this disorder.”

Katie’s estimate is two decades before an effective treatment. But for the next 20 years people will still develop MND, and other people – their families, loved ones, professional carers – will have to help them manage it. What does that involve?

“It’s such a desperate disease. The physical progression of MND causes people to lose their independence. They may be unable to feed themselves or dress themselves. They may also lose the ability to communicate. And finally they lose the ability to maintain their breathing pattern, which makes them prone to infections, and that’s what often causes them to die.”

There are no quick fixes in science. Motor neurone disease more than any other field has learned that lesson.

What, I ask her, is the support she most needs? It is money, equipment, people?

“All science is expensive. Funding for my work goes to pay the salaries of researchers, to buy the cells we use to work with, to buy the laboratory equipment we use. Funding is vital. One problem right now is that funding bodies tend to fund low-risk research – research where there is an obvious and clear outcome – rather than fundamental research that may take years to translate to a treatment. That’s why funding from charities and other bodies is powerful – because it provides a platform for further funding by helping solve basic problems. There are no quick fixes in science. Motor neurone disease more than any other field has learned that lesson.”

Finally, we talk about her career, its rewards and challenges, and specifically about the role of women in science.

“I enjoy my work tremendously” says Katie. “It’s incredibly rewarding. Although all of my patients die, they are an exceptionally wonderful group of patients and I see a side of human nature that I feel incredibly privileged to be exposed to. Of course I both do research and treat patients and that’s a powerful position to be in. There’s nothing more motivating for research than to be faced with patients who are dying with their loved ones sitting next to them.”

Many women that are successful in science have sacrificed having a family.

And is there a glass ceiling in science?

“Women in science goes right back to schools. The way science is taught is often aimed at males. If you think of your physics class it was all about how fast does a train go, a bullet travels, a car travels. It doesn’t appeal to females. Scientific equipment is grey metal and is designed by men. Studies suggest that, for example, if medical equipment that is used by female nurses is redesigned by changing the colour of the equipment, it is easier to use. And there is a glass ceiling in science. The grant process – grants last for three years – makes it hard for women who want to have children. Many women that are successful in science have sacrificed having a family. The good news, however, is that in science you are judged on the quality of your science, not whether you are a female or not. Science is cosmopolitan.”

 As part of its philanthropic activities, The Leasing Foundation has committed to supporting the work of Dr. Katie Sidle and her team at University College London. Jonathan Andrew (CEO, Siemens Financial Services), Andrew Page (CEO , CHP Consulting) and Professor Peter Thomas (COO, The Leasing Foundation) are leading this work.

Dr. Katie Sidle spoke at the Leasing Foundation Second Annual Conference in Paris, October 3 2014, about current challenges, and expected breakthroughs, in her work on MND.

CC BY 4.0 Science is expensive by Peter Thomas is licensed under a Creative Commons Attribution 4.0 International License.