EVs and Motor Neurone Disease

“It is really important that the public is informed on what really is happening and how far we are moving along. On the other hand, it is also really important that the public inform and feedback to the scientists on what kind of research they would like to see because we might have a different perception of what is important for patients and what is actually important to patients.”

Dr. Laura Ferraiuolo

Dr. Laura Ferraiuolo is a lecturer in the neurobiology at the Sheffield Institute for translation neuroscience, the University of Sheffield. She study motor neurone disease (MND), a neurodegenerative disease which patients typically die within 2 to 3 years from diagnosis. Since at the moment there is really no affective drug treatment for MND so her research focuses on the translational aspect, understanding what happens in MND and how motor neurone death can be prevented. Specifically, her research team found that the cells which normally support the neurones corrupt in MND and so her team are focusing on this specific cell types to understand what is it that they start doing wrong which then affects neurone survival and trying to stop them.

Does your kind of research involve EVs?

Laura Ferraiuolo: Yes so what we have recently found out is that one of the things that is actually goes wrong in astrocytes from MND patients is that the way they communicate with the neurones changed, not only they are not as supportive as they normally are compare to a healthy person but also they secrete bad molecules and do not secrete enough the good ones.  And this secretion is regulated via through EVs so what we have found in our latest study is that specific subgroup of patients that carry specific genetic mutation called C9ORF72, they secrete less EVs then healthy people and they secrete less of some of the micro adenase which are molecules that involved at the crosstalk between astrocytes and neurones and so the neurones are really affected by that and they don’t survive as well.  So in our study we showed that if we manage to blandish some of the molecules that are missing from the EVs then we can rescue the motor neurone and so we are really hoping to take the forward into a more therapeutic approach. So far we have tested everything using patient cells and so now we are trying to move into in vivo models.

Do you think EV research has grown over the last decade?

Laura Ferraiuolo: I think it has exploded really. My perception is that the cancer fields are really trying to understand how cancer cells communicate and how cancer cells spread and so on.  And neuroscience, which is my area of expertise, is trying to understand how EVs involved in for example getting rid of toxic proteins or proteins that are mis-folded but now we have started understanding that EVs are really used for cell to cell communication even just in healthy situation and is not only to get rid of garbage, but also they are there to modulate the communication between cells. So yes it has grown and because it is a new way of communication that we are now discovering and exploring further and further.

As it has grown, do you feel that there is a sense of community among EV researchers?

Laura Ferraiuolo: Yes certainly so the EV UK meeting is one of the fantastic examples. There are people from various disciplines and just heard talks from the neuroscience field that there will be more following in cancer. I had some very good discussions on how we can collaborate more and what kind of models, what kinds of instruments or techniques and what kinds of issues we all encounter working with EVs.  So definitely I do feel this sense of community that really bridges across different disciplines, and because of that scientific interest in what EVs do and what they carry what are the cargos regardless of these specific diseases or areas that you are studying.

As you had a talk today in the EV UK meeting, how did it go and what did you talk about?

Laura Ferraiuolo: Yes so today I presented some of the data that have been just accepted for publication and some very new data where basically what I was showing is that if you take skin biopsies from MND patients and people were healthy, and you reprogrammed them into astrocytes and you grow them in culture and you take the EVs from the medium in which they grow and then you look at what these EVs carry, what is their cargo, you will see that the cargo is very different so you can see immediately that what astrocytes from control from healthy people secrete to what MND patients secrete.  Not only that but the motor neurone disease patients population is very heterogeneous so that there are various genetic mutations that cause motor neurone disease but also there is the very large slice of patients 90% of patients that do not seem to necessarily carry a mutation so we called them sporadic because there is no family history of the disease.  And what we can see is that the cargo of the EVs is enough to actually distinguish different patients subgroups.   Now this is very important because the motor neurone disease patient population is very heterogeneous and this affects the way we treat patients so anything that can help us group together different patients might be very useful in terms of therapeutic approaches. So for example in terms of astrocytes toxicity as we were saying if we know that the patients that carry certain mutation affect a certain pathway in the motor neurones and patients carrying other mutation do not affect that pathway that is gonna really drive how we treat that specific patients subgroup and not the other.

Do you think EVs will lead to significant medical advancement?

Laura Ferraiuolo: Yes I certainly hope so and I do believe so.  I think that there is already indication that might be the case.  As we learn more on how different cell types communicate with each other and even cells in the same type communicate, we will be able to manipulate that communication and I think the recent years are really have highlighted how EVs are keep or in cellular communication so I think definitely they will be involved somehow in therapeutic approaches and I think they will lead understanding how they work and what they carry and we can manipulate them is definitely going to lead to therapeutic breakthroughs.

Do you think it is important for the general public to know about EVs and just in general to know about scientific research?

Laura Ferraiuolo: I think is essential, I think definitely the public should know what goes on in the research area, what are the most recent breakthroughs and what we are doing so I think it is really important that the public is informed on what really is happening and how far we are moving along which is really exciting on one side but is not really true that every day we find a therapy for something you know it is important that people understand that is a long road from the basic discovering in the laboratory to an actual drug that one day you can go to pharmacy and buy. Also I think that is really important on the other hand that the public and patient groups and carer groups inform and feedback to the scientists on what kind of research they would like to see because we might have a different perception of what is important for patients and what is actually important to patients so I think it has to be very much communication and again it has to be a bit crosstalk and does not break down between what are the need of research but especially what are the needs of patients.  I wake up everyday just so that one day my research can contribute to the development of a therapy so this is my driving force so of course I think the communication with that patient group is really important.

In your own words, how would you describe EVs to someone who never heard about EVs before?

Laura Ferraiuolo: I will describe them as teeny tiny vesicles of little balls that you can pack with a lot of information and then send them out to other cells.  It is a bit like the message in the bottle, then you leave out but it has a recipient and this recipient will then receive and open it bf read the massage and behave accordingly.

Recently have you heard of any particular type of research that really fascinated you?

Laura Ferraiuolo: I think there is really interesting research going on for example organelle transfer.  I think the idea that cell not only secret out EVs that carry proteins but can also carry organelles so that part of the cells can actually migrate to another one and can be functional.  I think that is really breakthrough and incredibly fascinating so actually just this morning during the EV UK meeting we heard about how mitochondria can be carry into vesicles and I find that extremely fascinating and there is a lot of research going on in that area how organelles can be moved across cells not only through EVs but also from nanotubes.  I think that is extremely fascinating and definitely it is something that I have been looking to in our area motor neurone disease research.

If you have a billion pounds, would that be the kind of research that you would like to invest?

Laura Ferraiuolo: What I will try to do is very much in the direction of patient stratification.  I think what I will try to do is to collect as much information as I could in term of genetic information, transcriptome and proteomics from a very large group of patients and healthy individuals and trying to understand what are the characteristics that distinguish different patients subgroups compare to healthy individual but also different patients subgroups amongst each other.  I would associate that to drug treatment and so try to understand what drugs work well for certain patients but not for another and so that we could tailor drug treatment better for our patients.

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