Wednesday, 21 October 2015

Helping scientists to find a cure for MND



My name is Sarah and I'm a member of the Sheffield Motor Neurone Disorders Research Advisory Group (SMND RAG) hosted by The Sheffield Institute for Translational Neuroscience (SITraN)

My lovely Dad had MND and died in 2011, not long after I joined the group. My Mum and Dad lived with my family for the last year of Dad's life. My husband and I were able to help Mum with Dad's care, we were able to give Dad the love and care he had shown all of us. 

Sarah and her dad who had MND and died in 2011
 
I felt frustrated there was no real treatment for MND apart from rilozule which can only extend life slightly. While googling research into MND, I came across a write up about the SMND RAG on the MND Association website. I applied to join and honestly didn't think I'd be accepted, I don't have a science or medical background.  

Before I officially joined I was given a tour of SITraN by Emily, a group member and scientist who also lost her Dad to MND. Talking to Emily and seeing the fantastic facilities at SITraN gave me hope for new treatments and eventually a cure for MND. The group particularly needed people with MND and people who had cared for someone with MND to advise on research projects from a patient/carer perspective. 

I went home and told my Dad I was joining the group, MND had taken his voice but he put his thumb up to me in support. I told him that one day I could play a tiny part in helping the scientists find a cure for MND. 

As a member of the SMND RAG I get to meet other carers, people who have MND and professionals who have worked with people with MND. 

Sarah (right) and other member of the Sheffield MND RAG at SITraN
We meet every three months in person and have email contact in between. We review patient information leaflets and make sure the latest research is included. Scientist give us lay summaries of their research to make sure they are easy to understand without a science background. We give advice on how easy or hard it is for a person with MND to take part in a particular trial and look for ways to make it as easy as possible. My favourite part is when the SITraN scientists talk to the group about their latest research, they're so passionate about finding a treatment for MND. 


The group at work

The group are a friendly bunch and I was made so welcome from the beginning. We always have time for a catch up over lunch, with cake!  

I feel proud to be part of such an amazing team and I know my Dad would be very proud of me too.   


By Sarah Wyatt

Sarah is a Photographer based in Derbyshire.
You can follow her on Twitter @S4R4H999.


More information on research at SITraN and the Sheffield Motor Neurone Disorders Research Advisory Group can be found on the SMND RAG website or in the latest SITraN newsletter.

The group always welcomes new members, so if you would like to find out more please email: smndrag@sheffield.ac.uk

 

SITraN also hosts research advisory groups on dementia and Parkinson's.
For more information and to get involved please contact Annette.Taylor@sheffield.ac.uk



Wednesday, 7 October 2015

Understanding energy generation, the holy grail of aging research in motor neurone disease



As a scientist working on MND I often get asked to describe what a typical day at work is like. Now the great thing about a career in science (if you are lucky like me!) is that every day tends to be different, it certainly is not your typical 9 to 5 office job (no offense to those who have typical 9-5 office jobs). 

But today was especially unique as I found out that my translational neuroscience MSc student, Laura Francis, came top of her class and was awarded both a distinction and the Johnathan Stone Prize. I was really pleased for her as she worked really hard, generated some interesting data and more importantly did not complain when I turned the volume up on the radio when Oasis came on. I had a slightly depressing moment though when I realised that Laura was born the year before I took my GSCE exams, in 1993. 

Laura is part of an up and coming new wave of young, enthusiastic scientists with bags of energy. I thought I was still part of that group, then I looked in the mirror and realised I had grown into a rubber faced 37 year old bloke with two kids, a dog and a DIY obsessed wife. Give it 15 years, I told myself over my fifth cup of morning coffee, she may not be as sprightly in the mornings then! Aging can catch up on you at any moment, as the great Kevin Keegan once said “those 32 and 33 year old players will be 34 and 35 in two years’ time at the World Cup if they’re not careful!”
 

Aging affects the body in many ways. Interestingly at a cellular level, the ability to make energy to help the cells in your body function properly becomes less efficient with age. This means as you get older your cells struggle more and more to take in fuel from the diet and turn it into fuel for the cell. This loss of function is also observed in people affected by MND even those who are middle aged and not classed as “old”, whatever that means? Many researchers in the field believe that MND may even be an early aging disease. 

Part of my work is looking to see how MND affects the ability of the cell to make energy. The energy generation system in cells is a complex network of interlinking pathways. These pathways are in balance and they work together to make energy, one pathway can upregulate its function to compensate for other pathway being downregulated and vice versa. 

I have a theory that in a healthy person there is a certain amount of flexibility in the metabolic pathways that is lost for some reason in MND. We have just recently published a paper in Neurobiology of Aging, where we took skin cells from patients and healthy controls and assessed the function of the two main energy generating pathways in the cell using a very cool piece of kit called a Seahorse bioanalyser kindly donated by Neurocare.

A dashing young scientist using the Seahorse bioanalyser

The bioanalyser measures the oxygen taken in by the cell and the hydrogen ions pumped out of the cell. Oxygen consumption predominantly originates in a part of the cell called the mitochondria which consume oxygen to produce energy. Hydrogen ions are a byproduct of glucose being taken into the cell from the diet and metabolised to produce energy. We found that skin cells from healthy control cases increased their mitochondrial oxygen consumption and decreased their hydrogen ion production with age. When you fluorescently labelled the mitochondria you could see them becoming more interconnected with each other with age to allow this increase in oxygen consumption to occur. This networking of the mitochondria is critical for their function.

Interconnected mitochondria in the skin cell of a healthy control case.
Interestingly the skin cells from MND patients lost this ability to interconnect their mitochondria and increase oxygen consumption. However, they did have the ability to increase their glucose consumption to cope with the defect in mitochondrial function. This metabolic flexibility may be one of the reasons that the skin cells don’t die in MND unlike cells in the central nervous system (CNS) such as motor neurones. We are now using human astrocytes reprogrammed from the skin cells of MND patients by stem cell technology to identify whether this metabolic flexibility is also evident in the CNS cells.

If we can understand why at a metabolic level aging is a risk factor for MND, we can develop rational approaches for nutritional supplementation to support healthy neuron metabolism. Then hopefully people who develop MND at 32 or 33 will reach 34 or 35 in two years’ time if they're careful, right Kevin?

 

Reference:
Allen SP, Duffy LM, Shaw PJ, Grierson AJ. Altered age-related changes in bioenergetic properties and mitochondrial morphology in fibroblasts from sporadic amyotrophic lateral sclerosis patients. Neurobiol Aging. 2015 Oct;36(10):2893-903. doi: 10.1016/j.neurobiolaging.2015.07.013.


By Dr Scott Allen 



Scott is a senior researcher in Prof Pam Shaw's group. His research focus is how MND affects the major energy generation pathways in the central nervous system and how the disease affects the metabolic response to aging. You can view his profile on Researchgate and LinkedIn to see links to his recent publications.