Dr. Patrick Flood

November 2014

For the first installment of the series, we’d like to introduce you to Dr. Patrick Flood.  Dr. Flood is a full professor at University of Alberta’s School of Dentistry with a cross-appointment in Microbiology and Immunology.  Dr. Flood has been a full-time researcher since the 1980s; and has been working in the Neuroscience and Neuro-inflammation field for the last seven years.


Parkinson Alberta (PAA):  In layman’s terms, how does your research relate to Parkinson’s disease?


Dr. Patrick Flood (DPF):  Parkinson disease like many chronic neuro-degenerative conditions, Alzheimer’s, ALS, Huntington’s, MS and so on, have both a neurological component as well as an inflammation component.  It is believed that the long-term nature of the degeneration that’s seen in Parkinson’s as well as Alzheimer’s and so on is partially or significantly due to the role of inflammation.  Parkinson’s is a disease in which there are a number of neurologic changes which result in an activation of the immune system within the central nervous system and that activation of the immune system contributes to the degeneration of dopamine energy neurons within the areas of the brain that produce dopamine leading to this long-term loss and eventual symptoms and disease that we call Parkinson’s.


PAA: Why did you choose to pursue research as it pertains to Parkinson disease?


DPF: I've always been interested in research and I've always been interested in how the immune system works and how inflammation works and how it contributes.  If you look at all the different aspects of inflammation…inflammation contributes to cancer growth, to neurodegeneration, to inflammatory bowel disease and a number of these very debilitating conditions.  So, the whole idea of how inflammation gets activated, how it progresses, how it really reflects in certain diseases and certain types of diseases was always an area of interest for us. We had initially started out looking at inflammation as a process and how it was regulated and what was involved.  As we developed some ideas about inflammation, we started to look at some of these debilitating diseases like Parkinson’s and Alzheimer’s and thought this is an inflammatory process that can eventually be controlled.  If we find the right combination of things and that by controlling that inflammatory process and perhaps even by reversing the inflammatory process, we may be able to affect at least a slowing of the progression of the disease, a removal of symptoms of the disease and potentially maybe even a way of not curing necessarily but at least reversing the debilitating effects of the disease over a longer period of time.


PAA:  What are the specific research questions you are trying to address and how would you explain the importance of these questions to a Parkinson community?


DPF: The major question that we’re trying to really look at is “what is the role of inflammation in the process?” and ultimately how can we affect a change in that inflammation so that the disease will alter in its progression.


Generally, it’s thought that the way Parkinson’s works is there is some anomaly.  It’s either a genetic anomaly, maybe it’s due to trauma, maybe it’s due to infection, or maybe it’s due to exposure to some neurotoxic agent or event that initiates this process of inflammation.  It’s the inflammation that over a period of time will start the process of degeneration; and as the cells degenerate it will induce more inflammation and so it’s very cyclical. You’ll see this type of cyclical process in Multiple Sclerosis, Parkinson’s and Alzheimer’s.  Eventually as the cells start to degenerate, they’ll induce more and more inflammation and that will drive the process over a longer period of time til ultimately most of the offending material that drives inflammation has been removed or destroyed. Unfortunately, in this case, it’s the cells that produce dopamine and so as the inflammation progresses; the immune system in the individual basically tries to destroy the cells that are quite beneficial to them.  And as it destroys those cells the loss of dopamine production takes place and you start to get the symptoms of Parkinson’s.  


So the key for us in a lot of these things is to understand when inflammation is activated, how it progresses over a longer period of time and ultimately to develop some anti-inflammatory treatments that may be effective, not only in stopping the progression of the disease, because unfortunately by the time a lot of people present with Parkinson’s, a lot of the destruction has already been done.


PAA:  So then your research takes into consideration all aspects and stages of Parkinson disease?


DPF:   One of the keys to Parkinson’s is understanding very early on how this inflammation is activated and progressing, and intervene at that time.  But secondarily if you’ve already presented with symptoms, how one can, in essence, reverse the process so that you now don’t have destruction of these cells but actually have regeneration.


Because inflammation is a process, you’ll see it everywhere on the body.  It begins when you may, let’s say, get a cut or a burn and you get that initial phase of destruction where cells will come in and try to get rid of the infection or try to get rid of the destroyed tissue.  Then they switch over to what we term a “wound healing phenotype” which means they’re now trying to rebuild the tissue that has been destroyed in a normal way.  Sometimes when it’s rebuilt incorrectly, you get scarring. Sometimes it doesn't rebuild very well because it never switches over to that rebuilding phase.  But in Parkinson’s, what we’re trying to do is try to understand why it goes first of all into inflammation, why there’s the destruction and how we can reverse that destruction by pushing it toward more wound healing phenotype so that it will actually regenerate the cells rather than destroy them.


PA:  That's incredible!  Were there any unexpected challenges you've come across thus far while looking into your research and if so, can you expound on one or two particulars?


DPF:   Finding the right model system; we have a number of different ways. There are genetic models as well as induced models where we can inject a neurotoxin and initiate this process of destruction.  Then we can intervene at certain times and say “Okay, what is going on there? What’s the nature of the inflammation that’s occurring and what types of anti-inflammatory treatments can we utilize that are effective but most importantly, how can we target those anti-inflammatory treatments directly to the areas that need them?”


Inflammation is a process that can be beneficial or detrimental. You need short-term inflammation to protect yourself against infection and so on but the problem is when it becomes chronic. If it’s a chronic inflammation, it’s unresolved, that the body doesn't say “Okay, that’s enough. We've done enough destruction. Now let’s reverse the process.” Then you get all of this long-term destruction like you see in many of these neurodegenerative conditions like Parkinson’s disease. So our major challenges are first of all trying to find the right model systems for looking at how we can reverse the process or how we can affect the process and second of all, how we can direct that to the site within the central nervous system without damaging the rest of the body’s inflammatory processes.


PAA:  Okay. Are there lessons that you've learned from the challenges then?


DPF:   Sure. Basically we’re trying to look at specific processes that we can use certain anti-inflammatories to reverse. Now, there has been a lot of data out there that suggest that folks who are on anti-inflammatory treatments – even in animal model systems that have been given an anti-inflammatory -- that it’s somewhat beneficial.


PAA:  How so?


DPF:   The data suggests that it helps to slow the process. But what we’re looking for specifically are the anti-inflammatories that are going to reverse the process. Instead of saying, “Okay, with 80% or 90% destruction we’re going to stop it right there"; we’re actually trying to reverse it so that a lot of these cells will try to regenerate. There’s only a certain class of anti-inflammatories that seem to be able to do that and so our biggest challenge is really to identify the process of how to reverse inflammation and to identify the anti-inflammatories that will actually do that process.


PAA:  That's fascinating. What are your thoughts on the future of research in Parkinson’s disease?


DPF:   Good question. What are my thoughts about the future of Parkinson’s? I think basically that the key to Parkinson’s will be early detection.  A lot of groups are working on trying to find markers that will indicate that there is a beginning of this inflammatory process. People are looking at various tissue, like blood or saliva and so on for markers of Parkinson’s. Because Parkinson’s like any other disease, the earlier you catch it, the earlier you identify that the process is actually going on, the more likely you are to be able stop it and reverse it.


PAA:  Okay.


DPF:   Many people have talked about stem cell regeneration stuff. Many people have talked about implantation and so on and so forth. Those have been only, modestly successful for a number of reasons. We would suggest that part of the reason is because of the inflammatory process that if you don’t do anything to reverse it or stop it, that replacing things is probably not going to be that successful. So I would think that perhaps the two areas that we may be able to effect major changes is to utilize some targeted genetic approaches.


PAA:  Makes sense.


DPF:   They talk about personalized medicine now, that there are certainly opportunities for personalized medicine in the treatment of Parkinson’s to replace some of the things that are being destroyed. But more importantly to try and stop the process early enough and to reverse it early enough so that we never get to the point where folks have lost virtually all of their dopamine production which is really the issue here.


PAA:  So does your research then apply to more than just Parkinson’s? Is it neurological as a whole or just specifically Parkinson’s?


DPF:   I think our research applies to a lot of neurodegenerative conditions.


PAA:  Okay.


DPF:   Because we’re looking at how the immune system behaves within a central nervous system which is a little bit different than how it behaves everywhere else in the body.


PAA:  Right.


DPF:   Parkinson’s is a good model for that simply because we know that it’s an inflammatory process, we know how it progresses during that inflammatory process; at least in the animal models and in some of the patient work that’s been done. So it’s a good model for looking at that and hopefully if we are able to affect a good, solid treatment for inhibiting the progression of Parkinson’s, then we’ll be able to use some of that in some of the other neurodegenerative conditions. They often talk about how Alzheimer’s is very similar in many ways because it’s a chronic inflammatory condition as well. So, the key there would be to stop the inflammation early. With Parkinson’s, it’s possible that we may be able to rebuild the cells or regenerate the cells that are lost in the process. Alzheimer’s is going to be a little bit more difficult because it’s really more of a cognitive problem and it’s losing the neurons that are responsible for cognitive processes as opposed to specifically but having said that, there are a lot of similarities between the two of them. Many of them have to do with inflammation and how we can affect a change and the progression of inflammation in the process.


PAA:  Theoretically, there’s a potential for a domino effect. You can find an answer in one that may help out in other places.


DPF:   Yes, for example, some of the anti-inflammatories that we’re using in the animal models of Parkinson’s that have been quite successful for us, we were also using other with conditions like ALS and Huntington’s and so on. We’re starting to move into those processes. We've actually shown that some of the anti-inflammatories are very effective in the treatment of inflammatory bowel disease for example. So that’s not a neurodegenerative condition but it’s an inflammatory condition.


Surprisingly enough, Muscular Dystrophy is an inflammatory condition that responds very well to these anti-inflammatories. So there are possibilities that we’ll be able to use some of these what we find in Parkinson’s to treat some of these other chronic degenerative conditions as well.


PAA:  I'd like to wrap it up on a more personal note; what do you enjoy most about your research and/or your job?


DPF:   What do I enjoy most? Working with students is one of the joys of the job, I mean to educate the next level or the next generation of researchers and so on and to get them as excited as we are about some of the things that we do. Science is getting a little more difficult just due to the funding conditions and so on and so forth. But working with really good folks, particularly the next generation of students, is always very rewarding. We've always been working with students and you always tell them, “If discovering something that nobody has ever known before is not enough for you, you’re probably in the wrong business.”


So the whole idea of bringing new knowledge to the human population and working and affecting something that you feel will be a legacy; that will actually improve the human condition is the joy of the job.


PAA:  Thank you so much Dr. Flood.
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