During the 25th International Symposium on ALS/MND there were two dedicated sessions for researchers to view over 300 posters. These posters varied from brain imaging to therapeutic strategies. But what is a poster? In this blog I’ll explain more about the session, as well as highlight some of my personal favourites.
A biomedical or clinical poster, is in many ways, like an advertising poster. Researchers use colour and text to present their research in a visual way, to engage and discuss their work.
This year’s poster sessions during the symposium were extremely busy, with large crowds often surrounding just one poster and its presenter! The whole room was a real ‘buzz’ of excitement with poster presenters benefitting from the interest and discussion of their work from researchers around the world.
Our Lady Edith Wolfson Clinical Research Fellow, Dr Jakub Scaber (University of Oxford) said: “I didn’t expect such an interest in my work, I ended up being in discussions for well over half an hour – I didn’t even get chance to remove my coat! I really enjoyed the symposium and got to speak to a few more people than I did last year!”
Stem cells were a key component of the symposium, as described in our earlier blog report, and Dr Scaber showcased them in all their glory – he even matched the colours on his poster to his stem cell images!
Dr Scaber is hoping to characterise the protein TDP-43 and how it becomes uncontrolled in motor neurones. He does this by taking skin cells from someone living with inherited MND caused by the C9orf72 mutation, and re-programming them so that they become human motor neurones. Inherited MND is rare (5-10%) of total MND cases, but C9orf72 is the most common gene mutation found in these individuals.
Dr Scaber said: “We detected elevated levels of TDP-43 protein in these motor neurones, which was arranged in the cell incorrectly. However importantly we didn’t detect this at the molecular level, and I will be conducting further research to investigate this further in 2015.”
Using DNA to target what goes wrong in motor neurones
Association-funded PhD student, Helena Chaytow, presented her highly commended poster on using DNA to target RNA (our cell’s copy of DNA) processes that go wrong in MND.
Helena said: “My research looks at the manipulation of RNA processes to try and replicate conditions previously shown in the motor neurones of people living with MND. My poster showed that short sequences of DNA can be directed at these specific RNA processes that go wrong in MND. This means that not only could my research lead to a cellular model for MND, but by using DNA to target these processes, this could also have potential therapeutic value.”
Therapeutic strategies posters highlight gene therapy
After receiving a comment on our blog, I decided to check out the therapeutic strategies posters, as the first four posters were looking at gene therapy for MND. Unfortunately, the first poster presenter was not available during the symposium to discuss their work, but I thought I’d comment a bit on their abstract (P264), which you can view here on our website.
Dr Shin Kwak from the University of Tokyo’s abstract was about the use of gene therapy for ‘sporadic’ MND. The term sporadic refers to the more common non-inherited forms of the disease, so how could gene therapy be useful?
Improving the proof reader
Well, the enzyme ADAR2 is responsible for editing our RNA, checking for any spelling mistakes within the genetic code, before the cell uses it to make a protein (find out more about DNA, RNA and proteins here).
This ‘proof reader’ is essential for making sure no mistakes occur within the cell. However, in MND ADAR2 is found to be less active and slower than it should be – meaning some mistakes ‘slip through’ causing the resulting proteins to become faulty. Therefore Dr Kwak asks ‘can we make this enzyme active again?’
By using gene therapy, the researchers added a corrected gene that targets ADAR2 to a harmless virus. The beauty of viruses is that they only infect the cell’s they want to infect (eg the cold virus only infects your nose and throat cells). This means that the researchers could specifically target motor neurones, delivering the new ADAR2 gene to the cell.
Does it work? Using mice that modelled sporadic MND, the researchers found that ADAR2 gene therapy prevented motor neurone death with no apparent side effects. The next steps would be human testing. However, it is important to stress that MND is incredibly complex and we know that multiple pathways go wrong during the disease. Therefore, if inactive ADAR2 is involved, this gene therapy may correct this disease pathway. However, it is likely that other disease pathways would need to be targeted too. We will just have to wait and see if this gene therapy from Dr Kwak makes its way to human clinical trials.
Delivering therapies to the right place
Because viruses can be highly selective, more and more researchers are using them as potential vessels for transporting potential gene therapies.
Andrew Tosolini (University of New South Wales) who helped us report from the symposium, is targeting motor neurones in this way in healthy animal models of MND.
Andrew said: “My PhD studies have focused on optimising ways to deliver compounds into spinal cord motor neurons in both the healthy mouse and rat. The first set of studies focused on locating the exact area where the nerve communicates with the muscle, a region called the neuromuscular junction. I created a map of these locations and then used them as target points to inject a neuronal tracer which would ultimately label the motor neurons that supply the injected muscle. I then targeted the neuromuscular junction with a virus to determine if I could deliver genes into the spinal cord motor neurons.
“This successful work has significant ramifications as it can aid the development of viruses that encode the gene sequence for potential therapies that can be delivered into the spinal cord motor neurons in a minimally invasive and therefore, clinically relevant way.”
The future of gene therapy
Gene therapy seems to be getting more and more traction nowadays thanks to huge advances in genetic research. It is also interesting to see that researchers are now testing the technique in non-inherited forms of MND.
The next steps will be for the researchers to investigate whether or not these results can be replicated in humans, bearing in mind that multiple pathways are involved in the disease. However, if gene therapy can halt one pathway, then it is possible that it could be used in combination with other potential treatments that target the remaining pathways.
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