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VIDEO: Are you curious about the ageing brain? Alzheimer's disease research

Mr Conor Nelson and Associate Professor Debbie Young work to create new cures for memory loss, such as those seen in Alzheimer's disease and other dementia related illnesses.


Enjoy this video interview of Mr Conor Nelson and A/Prof Debbie Young here or read the transcript to learn more about their research into Alzheimer's disease treatment.



Transcript of interview with Mr Conor Nelson (CN) and Associate Professor Debbie Young (DY) by Hayley McLarin (HM)


DY: Hi, I'm Associate Professor Debbie Young and I am located in the Department of Pharmacology and also the Centre for Brain Research at the University of Auckland. I have a long standing interest in the development of therapies for neurodegenerative diseases and these include gene therapy strategies as well as antibody based strategies.


CN: Hi, I'm Conor Nelson. I'm a second year PhD student in Debbie’s lab. My current project is using an antibody therapy to treat diseases of ageing, specifically, dementia and other dementia associated illnesses.


HM: Debbie and Conor thank you so much. What do you hope to achieve with the research?


DY: What we are trying to achieve with our research is to develop a therapy that may have applicability for people who suffer from conditions associated with learning. This is important because we've shown that in preclinical models we can actually improve learning and memory function.


HM: And Debbie, Conor is working with you on this project?


DY: Conor is taking one step towards this goal by now examining whether this treatment could actually be effective against a neurodegenerative disease like Alzheimer's or Huntington's disease.


The project of interest that Conor’s working on is based on the development of an antibody-based therapy that we think might have applicability for improving learning and memory problems for people with dementia and also age related cognitive impairment.


HM: So tell me Debbie, how long has Auckland Medical Research Foundation been funding you?


DY: The Auckland Medical Research Foundation has been funding me for around 10 to 15 years for a number of different projects. Back in 2013, the AMRF funded a piece of work that made some pivotal findings in defining how these antibodies actually work to cause improvement of learning memory in preclinical models.


HM: What are the potential outcomes for you? What are the next steps from here?


DY: Conor is going to work on a specific part of this research programme, and he's going to talk more about how his work will contribute to an understanding of how this therapy might actually work in the context of neurodegenerative disease.


HM: So first off Conor, can you please tell me, what is antibody therapy?


CN: To understand antibody therapy, the first thing you need to know is what an antibody is. So basically it is a collection of proteins that your body produces to bind to foreign proteins and normally this would be binding to something like bacterial viruses, but we can actually design these antibodies in our lab to target specific things. Some people use them to target proteins that cause disease, or in our case, we are targeting a receptor that acts like an on-off switch. So the binding of these antibodies to a receptor can change the way the cells act and hopefully encourage them to survive.


HM: And tell me, what are the symptoms and effects of Alzheimer’s disease for a person?


CN: General estimates tend to be at that about 11% of the population, or one in nine people above the age of 65, will suffer from some dementia associated illness. In these illnesses you tend to see general cognitive decline, you see losses in spatial learning and memory, you see a whole lot of issues that can make it really hard to just live your life. It's really important that, especially as our population continues to get older, we manage to make it so these people can live their life to the best of their ability and improve their quality of life. Prophylactic therapies that come before the onset of symptoms would be amazing.

Our therapy that we've developed will hopefully offer some therapeutic benefit in both cases. Our current belief is that this therapy should be more beneficial if it's given before disease onset, but our data does suggest that it can potentially halt the progression so to stop any further deterioration from occurring.


HM: And Conor, what is a prophylactic therapy?


CN: A prophylactic therapy is a therapy that is given to prevent something. Normally whenever you think of a medication, you think of something like an antibiotic where you end up going ‘okay, I'm sick, I'm taking this drug and this will help clear the illness’. With the prophylactic, it's something more like what you would think of with vaccines where you go, ‘okay I'll give you this medicine before you get sick and this will prevent the disease from ever happening’, hopefully!


HM: Are you looking to treat Alzheimer’s disease or are you hoping to be able to prevent it altogether?


CN: One thing that's quite tricky with a lot of these age related illnesses is quite often you don't know who's going to get them before they actually start. So in some cases, you can look at genetic or environmental factors, for example, people who've had multiple traumatic brain injuries like concussions are more likely to develop Alzheimer's disease. You also see that with a range of other factors, but as a general rule, with this sort of therapy, what you need to be looking at is the early stages of the disease. So once people start to have mild cognitive impairment or just some level of cognitive decline that's when you want to target this therapy. Hopefully, if you target it early enough, you may be able to actually recover a little bit of that functionality, but even just being able to stop any further progression would be absolutely amazing and miles beyond what we currently can do.


HM: Conor, what prompted you to focus on this area for your research career?


CN: I'm sure that everyone has known someone who has some form of dementia, and they've seen the sort of deterioration they experience. For me, so much of what I think of myself comes down to my experiences, my memories, the things that I associate as being part of me and how much that's just purely cognitive. The idea of having some sort of constant decline is honestly kind of terrifying. It would be amazing to be able to stop some people from having to experience that.

There are some therapies available which do help alleviate symptoms for people but being able to offer something that will actually change the course of someone's life would be absolutely amazing.


HM: And how do you go about doing this research?


CN: Basically, what we ended up developing is a designer antibody and this antibody will bind to one protein and one protein only, this is one subunit of the MDA receptor. These receptors are heavily implicated in the processes of learning and memory. They act like switches which control a whole bunch of different pathways within the cell.



These pathways can either encourage cell survival or cell death. A little bit of cell death is perfectly normal within the brain, and that's actually quite healthy, but where you end up with a problem is when you have the cell death signalling massively outcompeting the cell survival signalling and that leads to neurodegeneration. One thing our antibodies are able to do is they are able to preferentially inhibit this cell death signalling and allow the cell survival signalling to take over. As a result you end up getting more cells surviving and that should hopefully allow us to halt this process of degeneration.



Once we end up refining this therapy and we find it does actually work in various preclinical models with either reversal or prevention of this disease process; then we modify it to ensure it's 100% safe for human use. That is when we would then move forward, see if we can take it into a clinical trial and give it to patients with the disease to see if we can modify their disease progression.



HM: Conor, I understand you were awarded the Helen Goodwin doctoral scholarship. Congratulations. That must be a huge relief for you to know that you are being funded to carry out this work.


CN: This work wouldn't be possible if it wasn't for Helen Goodwin and the Gooduck Charitable trust. They have ended up funding this entire PhD scholarship for me. As a result, this means I can focus on this work without having to worry about my finances in the meantime, because I know some PhD students are constantly trying to work part time jobs to try to facilitate their study. For me, I can just focus on my research, which means that hopefully this will result in a much better outcome for the project.


DY: Donors play a pivotal role in this work because essentially developing a drug, from a concept in a lab right through to something that is used in people, is actually a long drawn out process, and every single piece of research counts towards achieving that goal. Just having a small project that might take a couple of years is really important to building that picture so that when we actually get to the stage of being able to test this treatment in people, we're going to be very certain that we have an idea of how this treatment is going to work and whether it's actually going to work in humans as well.


HM: What keeps you motivated? What keeps you wanting to work in this area?


DY: It’s that next discovery. It's the unexpected discovery. So you have an idea when you do this research, what you predict you might find, but then you might get something totally the opposite. It's that sort of contradictory result that basically gets my brain almost in hyperdrive, thinking, well this is not how I think it should be working and maybe there's some other explanation. I've always liked things like puzzles, doing Sudoku and things like that, so doing research is right up my alley because it's always finding the unexpected, and then trying to figure out how come I got this unexpected result - maybe there's something in this result that's leading me down a different pathway. So this research programme that started as quite a simple research programme developing a therapy and has now grown from two arms of different lines of investigation, to almost like an octopus. Different lines we're trying to chase and looking at things in our preclinical models that determine some of those factors that potentially can change an aged brain back into a young brain. So, those are other projects that I'm keen to get off the ground with other students.


HM: Debbie and Conor thank you so much. I have really enjoyed talking to you. I felt that I’ve learned so much today and I am sure that everyone else who is watching will have to. I really appreciate your time.

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