Oxidation Resistance 1 – tackling oxidative stress

MND Association-funded researchers, Prof Dame Kay Davies and Dr Peter Oliver, both based at the University of Oxford, have identified the oxidation resistance 1 (OXR1) gene as a neuroprotective factor in MND.

Published in the journal Brain on 9 March 2015, Prof Davies has shown through their recent research in mice that OXR1 may serve a new target for future drug development.

We’re funding Matthew Williamson’s PhD studentship to follow up this exciting research. Find out more about this and the other research projects funded by the Association in our newly updated Research we fund information sheet.Read More »

Major new research finding raises some old questions

Hot on the heels of ‘Brain Awareness Week’, comes ‘National Science Week’, with the University of Sheffield enthusiastically organising a numerous activities in their week-long Festival of Science and Engineering, including today’s Open Day at the Sheffield Institute of Translational Neuroscience (SITraN). This event was to include talks by Dr Chris McDermott and Prof Pam Shaw on MND and the role that SITraN plays in the search for effective treatments for neurodegenerative disease.

Unfortunately…… last night’s snow has put the kibosh on that, so instead of heading up the M1 to Sheffield, I decided to use some of the saved time to catch up on some reading – in particular a recent paper that came out in the journal Nature, from an international consortium, led by the scientists from the Austrian Academy of Sciences in Vienna.

The best seven pages in ten years

A senior MND researcher emailed me to say it’s one of the best papers he’s read in the past 10 years and I can understand where he’s coming from. Not only does the research identify a previously unknown cellular process that causes selective motor neuron degeneration, but it also appears to tie together several of the pieces of the pathological jigsaw: disruption of RNA metabolism, oxidative stress and programmed cell death pathways.

As impressive is the sheer amount of work that has gone into this seven-page paper. OK, there are also several extra pages of online supplementary material (one of the great benefits of online publication) but I reckon there is the equivalent of at least three PhD theses and several years of work in there!  

In a nutshell, the researchers created a mouse that has a defect in an enzyme called CLP1 and these mice develop progressive motor neuron degeneration. I’m not going to go into the detail, but rather focus on one interesting item that was buried in the text.

Genetic environment matters for CLP1

When researchers initially tried to create the mice they found that the mice all died well before birth. So they tried using a different strain of mice, but got the same result.

A third strain produced live mice, with normal numbers of motor neurons at birth. However from about the age of four months, these mice then developed a progressive muscle weakness and loss of motor neurons over the course of several months.

The paper focuses in on what’s going on in these mice, but it also raised additional questions for me, such as:

“Why did these mice survive into adulthood, when two other mouse strains didn’t – and is there something different in the genetic make-up of these mice that has basically protected them into adulthood rather than killing them as embryos?”

MND Association funded research on genetic environment

Other groups have noticed that when SOD1 mice are bred on different background strains, it can have a profound effect on disease progression and survival. This brings us nicely back to SITraN, as Prof Shaw and her colleagues are looking at precisely this issue, in an MND Association-funded collaboration with Prof Caterina Bendotti in Milan.

They are looking at the gene expression profiles (basically which genes are switched on and off) in the motor neurons of two strains of SOD1 mice, one of which develops the disease and later age and also lives much longer.  By working out patterns that are linked to specific biological processes, they are starting to pinpoint pathways which are driving the disease and also which ones might be slowing the disease. Some of their findings were presented at the most recent International Symposium (Abstract C61).

If there are protective genes at work in the mice, might the same be happening in humans?

The search for ‘good’ genes hots up

I’m often asked about Steven Hawking – how come he’s lived so long?  For years, one of my pet theories has been that there is something in his genetic make-up that didn’t stop the disease from occurring, but is ‘pushing back’. That’s becoming an increasingly popular and productive area of investigation – as genetic researchers extend their focus from finding ‘bad’ genes that cause or predispose people to develop MND, to potentially ‘good’ genes that might slow down the disease. A couple of candidates have been identified, most notably the EphA4 gene.

The search for these disease-modifying genes needs joined up collaboration between researchers around to world and it’s heartening to see how everyone in the field is starting to get together to pool their samples and data, which will allow the genetic profiles of those with exceptionally slowly progressing MND to be analysed in much larger numbers than ever before. If good genes can be identified and their roles understood, it will open up exciting new treatment opportunities.

It almost time for my annual upload of matters MND research!

Whilst I try and keep up to date with what’s going on in the field for the rest of the year, it definitely goes in peaks and troughs. One ‘peak’ occurs in May, when I’m reading through the Symposium abstracts for the first time. Another is at the end of our research funding cycles, when Sadie, Marion and Natasha have done all the hard work of getting the applications out to review and comments back again and final decisions have been made on what we’re able to fund.

At the Symposium I get to hear more about those abstracts that really sparked my interest in May. This year, I feel I’ve been slightly more organised than usual and I already have a list of poster presentations I’d like to visit. (It’s a much harder task to decide which posters to visit compared to which talks to listen to- there are more posters!). Part of this organisation is that as the abstracts have been available and online for almost three weeks now I really don’t have an excuse not to do any work before I get there (you can read them too – here) !

The grants that we are funding give me a chance to personally connect with some of the research underway. I might have the opportunity to catch up with some of the researchers working on these projects. It’s always good to put a face to a name, and occasionally I can point them in the direction of someone that they might be interested in collaborating with. Alternatively, I might see that a presentation being given at the Symposium has links with research we’re funding.

As well as learning about the new insights into the understanding of the various aspects of MND, the lab nerd in me is also on the look-out for novel experimental techniques! How people get the results is almost as interesting as what they found. (If two people can get the same results via two different methods, it gives us extra confidence that the results are right – this confirmation or repetition of results is a fundamental principle of scientific research).

I’m particularly looking forward to hearing what everyone’s talking about at this year’s Symposium, I hope that I can give you a flavour of what’s its like in the final preparations and attending this buzzy and exciting event over the next few weeks.