How an common anti-fungal drug could help stop brain disease

good afternoon my name is dr cameron jones and i'm an environmental microbiologist and this week on the live stream i have some really fascinating research that i want to bring to your attention and it is focusing on another type of problem that has a strong microbiological underpinning and it is particularly important because we're going to be focusing on not just infections and asthma related risk respiratory problems caused by fungi but we're going to take a look at how these are possibly linked to a range of different brain diseases or brain disorders and so the topic of today's live stream is how a common anti-fungal drug could help stop brain diseases and to put this in context i want to share a bit of a personal story with you because many years ago when i was doing some postgraduate training in industrial microbiology one of my lecturers was warren baker and i want to tell you this personal story because it sets in context why i'm bringing you this live stream and why this has always been a topic that i have been very interested in warren baker was one of these classic academics he was a chemist by profession and he had very dense lectures that he used to bring to us he had an encyclopedic knowledge of chemistry when he retired i heard soon thereafter that what caused him to retire was because he had early onset dementia and obviously this impacted severely on his ability to enjoy his retirement and it ultimately was the reason that um he eventually passed away and if we look at the experience of brain disorders here in australia over the next 40 years they are going to cost us approximately 1 trillion and get this 16.4 million australians are going to end up being impacted by various different brain disorders and so the live stream today i want to focus on some breaking research and this really is fundamentally important research because it is something which many of you want answers and without medical intervention there isn't going to be any way of reducing the severity or the impact of these various different brain diseases because a lot of the treatments that medicos can give you really just slow the progression but they don't stop it so scientists need to come up with answers to this and so that is the topic of today's live stream okay so what are we focusing on i need to give you a bit of first principles about brain biology well the brain consumes approximately 20 percent of the body's energy now put another way this means that your brain uses approximately 20 percent of the oxygen and blood to sustain it 25 of that energy goes to help maintain the cellular processes going on inside your brain and the other 75 goes to the signaling and that is how we actually learn retrieve memories and actually the whole process of cognition so think of that 75 goes for the signal transmission and 25 goes to supporting the cells so when we're looking at what could go wrong really it's a one of those two outcomes signal transduction or maintenance of cellular control now neurological disorders are increasingly recognized as a major cause of death and disability worldwide and to put this in context an outstanding publication came out in may 2019 which essentially reviews the impact of neurological and neurodegenerative disease on a worldwide basis now a lot of the links to these papers are going to be in the show notes at the bottom of the live stream and certainly if you're listening to the podcast they'll be in the show notes there but for those of you who are tuning into the live stream now i'm going to make sure that the references are all put up after the live streams ended so you can retrieve these papers yourselves and you can validate that what i'm saying to you is in fact uh relevant and potentially relevant to you or a loved one because you might want to bring this to their attention and so this particular publication is looking at the global burden of these diseases on humanity and they're talking about the fact that as of 2016 the range of neurological disorders are the leading cause of dailies and this is disability adjusted years and essentially think of this as the years lost when you could have been having good health and so there are 276 million years lost think of that and then it causes nine million deaths this is just a horrendous number and is really under appreciated and that's why i wanted to focus this week's live stream on this range of neurological diseases because they are not well discussed and certainly we're putting so much attention now focusing on sars covid covid2 another type of pathogen and in a sense the cutting edge research which is coming through now is suggesting that a lot of these neurodegenerative illnesses and diseases may in fact have a strong microbiological component and i think my old professor warren baker would be very pleased to read about this in the literature because the paper that i'm focusing a lot of attention on is focusing on a chemical and its mode of operation is anti-fungal i think he would have liked that but for all of you who potentially have loved ones who currently or potentially suffering with dementia or alzheimer's or a range of different adverse brain issues this research is something that you should be aware of and certainly you should discuss this with your healthcare provider and medical doctor now what are some of the solutions that are hiding in the research literature well one of the papers came out in 2020 and this is looking at one of the components that i mentioned before as i said there's signal transduction and then there is the maintenance of the cells themselves and so this publication is providing two opportunities to modify the way these cells behave within the brain and that can only be a good thing and again as i mentioned for those just starting to tune in the literature references to this will be in the show notes to this live stream and in the podcast but this publication just came out a couple of months ago and what it is stating is that there are two treatments for changing the mitochondria and again i've done whole live streams on mitochondria but mitochondria allow the cells in your body and in your brain to utilize oxygen and convert this into energy and there are a whole range of disorders including some induced by environmental fungi that are considered mitochondrial illnesses in that they disrupt the normal behavior of the mitochondria at the cell level and this publication is suggesting that alzheimer's disease traumatic brain injury depression and parkinson's disease all fall under those illnesses that have a very strong mitochondrial dysregulation now let's go back to biology 101 in all of our cells we've got a range of objects called organelles these organelles allow the cell to carry out its activities and one of the types of organelles in all of our cells including our brains is something called the mitochondria and this strange word allows this organelle to do something very important and powerful in our bodies and it takes in glucose or sugars and oxygen and converts it to carbon dioxide water and energy and this then allows the cell or the brain cell to carry out those functions like signal transduction and so the point of these papers is that they are trying to positively interfere with the mitochondria to get them to behave properly or to behave more in a normal manner and if they do this the aim here is to improve these negative neurodegenerative outcomes and so the point of this publication in june 2020 is to use a dye called methylene blue and then something called photobiomodulation which is a variant on something called photodynamic therapy and for any of you who don't know about photobiomodulation or photodynamic therapy i urge you to key in these words into pubmed and retrieve some fascinating research on the impact of photobiomodulation but in a nutshell it is using light to positively interfere with brain activity and when i say interfere is to reset the mitochondria in a sense and things like methylene blue which themselves are well anti-fungal have well-known anti-fungal properties show good potential of being able to change the mitochondria from a dysfunctional state to a more normal functional state and there's some excellent fundamental research appearing in the research literature i urge you to look into this now i want to take you on to a another story in the journey of the relationship of pathogens to adverse brain behaviors and one of the papers is on parkinson's this came out a couple of months ago and parkinson's disease affects 6 million people worldwide and the adverse symptoms really are movement disorders but what this research is showing is that in the brains of people with parkinson's they have been able to determine that they are in a sense invaded with fungal pathogens and if we look at some of the tables extracted from the publication it is a lot of the common fungi that we see in water damaged buildings now i'm not stating that definite exposure to humans to water damage buildings is going to cause parkinson's disease but there definitely is a connection with a lot of the common fungi found in these known habitats that have adverse health impacts especially on the respiratory symptoms of people and those with parkinson's disease are showing a lot of these same dominance of microbial invasion and you can see alternaria cladosporium penicillium aspergillus various different candida microorganisms why are these microorganisms over represented in what is considered essentially a sterile area inside the brain this is very very important research because it is suggesting that there is something called poly microbial invasion which may predispose individuals to developing these adverse brain dysfunctional symptoms and poly microbial invasion may come down to the fact that an individual had a long history of being subjected to conditions that were microbiologically unfavorable meaning that they had illnesses caused by various different microbes there's another school of thought that the number of illnesses throughout one's life that are caused by bacteria yeast and fungi could conceivably predispose this cohort to developing abnormal brain problems but i want to put this in context because as you know each week i talk about water damage buildings usually and we can just pick one of the excellent papers from 2007 right this is talking about research from 2004 essentially 16 years ago and in the united states the economic impact of water damaged buildings and the adverse impact of mold exposure on people cost approximately 3.5 billion dollars annually and the key modifier here is to maintain water damaged buildings and dilapidated buildings and put them into a fit and proper state so there is general consensus in the academic and medical research community that exposure to dampness and mold substantially increases the risk and predisposes people to suffering a range of adverse health symptoms but what if the impact of these bacteria yeast and fungi goes beyond allergy goes beyond sinus infections and impacts potentially on the brain and we just have to look at one of the major think tanks around fungal pathogens gaffy in the united kingdom they are champions of making a connection between exposure to fungi and their adverse impacts on human health and they state clear research that fungal pathogens cause 1.5 million people to die annually fungal diseases were relatively rare until the 1950s with the introduction and widespread use of antibiotics which as we all know leads to antibiotic resistance meaning that these microorganisms that the antibiotics were meant to kill and control they've adapted to those chemicals and now they're even more virulent as well in the 50s advances in intensive care advances in cancer therapy the use of corticosteroids all create immunocompromise various different aggressive cancer therapies also use agents which cause widespread amino compromise and this is leading to more fungal infections in immunocompromised individuals so fungi do more than just causing fungal allergy they also cause direct infection like sepsis and to put this in context 150 people die every hour from fungal infections but now we come up to the climax of today's live stream this paper came out two days ago on the 14th of august 2020 and again you're going to want to retrieve this yourself for anyone that you know who is suffering brain disorders bring this to your medical practitioner to the clinician talk it over with them find out how they can potentially incorporate this into treatment modalities but as a microbiologist i think that this is fundamental cutting edge science i think it's a wonderful wonderful publication we're going to get right into what this publication says put this in context dementia is a bit of a catch-all term it's considered to be an age-related disease and there are lots of different types most of the drugs and treatments only delay symptoms and this concept of brain inflammation is certainly considered a new target location for drug development this neural inflammation is very similar to what we are seeing emerging in the fungal water damage building issue of neuro inflammation biotoxins causing inflammation either in the respiratory tract or causing issues like chronic fatigue which are considered to have a very strong inflammatory component so you can see that there is a strong connection with these pathogens and other issues that are not even considered related to brain dysfunction but in this publication they're saying the scientists are providing very clear evidence of how they can modify the negative impacts of dementia in by modifying neuroinflammation i'm going to just jump into some of the key research and like a lot of medical and scientific research they use a model which is mice and we really have to thank the 40 mice that participated in this particular research and i want to talk about the two experimental systems that the mice were put into so that the scientists could determine the impact of memory loss and the dementia related alzheimer's disease type symptoms that they needed to induce in these mice to work out whether a drug that they gave them could in many cases reverse or counteract the alzheimer's disease type symptoms so just think about this there are 40 mice they were placed in two different type of experimental chambers one is called a morris water maze and just to describe what happens to work out the relationship with memory is that the mouse is placed into the water maze obviously it doesn't want to swim in the water there is a platform submerged at some location within the water maze so once the mouse swims to the platform it obviously is no longer needs to swim now they scientists use a camera to film how long it takes and where the mouse actually swims to because over time they do this on different days and they can determine whether or not the mouse can remember where the platform is and how long it takes the mouse to get to the platform on different days the other type of experiment is by placing the mouse into essentially two rooms one which is light and one which is dark and one of the rooms has a negative experience and so the aim here is to work out how long it takes the mouse to remember that when it goes into that room in this case the dark room without the light it gets the shock and so it obviously doesn't want to go there and get a shock so again the aim of these two experiments is to measure the ability of the mouse to remember the negative consequences of not being able to work out how to not get the shock or continue to have to swim around until it finds the platform so what is this breakthrough drug well it's called myconazole now you're probably thinking what on earth is myconazole well the chemistry formula is on the right hand side but it is the active ingredient in dactarin it is the active ingredient in common pharmaceutical pharmacy-based antifungal medications it's commonly used to treat skin infections yeast infections and ringworm all of us have probably used it at one time or another now i am not suggesting that you go out and get some duct taron and rub it on your head or eat it or inject it you do want to take this publication though to your healthcare provider or your medical doctor and discuss it with them find out how and where what the opportunities for this new drug are as i said the paper came out two days ago i don't imagine that it is currently applicable for people quite yet but it will be i'm sure and this is really breakthrough research from microbiological point of view and from the viewpoint of standard science this is outstanding research i'm going to explain to you why the key findings show that myconazole attenuates memory impairment in mice where they induce alzheimer's disease and just think as you're looking at these slides i'm going to put up the next couple lps treated mice this is a way of chemically inducing alzheimer's disease or dementia and the legend is color coded in the bar graphs that i'm putting up obviously the control mice nothing happens to them they're just left normal the mcz mice they are injected with this myconazole this is the experimental drug the anti-fungal drug the lps mice they're the ones who are induced to have dementia and then we have importantly the red colored bar graph these are those mice that have dementia they have induced dementia symptoms in the mice but they also give them the myconazole and look at the testing trial in the mice being able to remember that they don't like getting shocked when they go into the dark room and you can look at the height of the bar graphs which shows the step through latency how long it takes them to make a decision to stay in the light or go into the dark and you can see that for the normal or the the mice given the normal nothing or given micronasol they show a fast response the poor old mice that have induced alzheimer's disease it takes them a long while to make a decision on which room to go to but those mice that are responding to the drug even after a short period of time are just under the normal control group and that is fascinating breakthrough research showing that this drug attenuates memory impairment let's look at another key set of findings myconazole reduces neuroinflammation in the hippocampus of the mice now what is the hippocampus well this is the area of the brain that regulates motivation emotion learning and memory really important region of the human brain and obviously in the mouse brains as well and so again looking at the color coding here the lps they're the poor old mice that are having an induced brain injury and you can see that the amount of neural inflammation in this oh hello again we had a slight power failure so i guess this is covered iso lock down problems in any case i'm going to continue on with the final few slides talking about the potential impact of nikon azole and what happened to these mice and so i was just getting around to talking to you about how in the mice which had been uh unfortunately induced to have a brain injury they wanted to look at the neuro inflammatory response in these mice and so they looked at something called protein expression and on the right hand bottom part of this slide this is a gel electrophoresis and the density of the colors or the bands shows you how much protein expression occurs and you can see that in those mice which have dementia problems you have a huge amount of protein expression this is shown in the blue graphs but in those mice which are given micron azole that is the red graphs the amount of protein expression reduces and this is really really really fundamental important information now i just want to check before we were interrupted about the previous graph we were talking about the hypocampus about motivation emotion learning and memory and in these sections when they actually stained the sections of brain they were able to determine that there was far less neuroinflammation in those mice that were treated with the miconazole and so the final graph as i said is talking about something called cytokine response and any of you who have been following the sarskovic ii virus impact was probably heard about cytokine storm we know that cytokine storms occur when the body is under attack in a sense and it's mounting an immune challenge and so they're able to determine that increasing the concentration of micon azole reduces the cytokine production and by reducing the cytokine production you are reducing the inflammatory impact on the brain so what did the scientists conclude in this landmark study it states that mcz or micronazole could inhibit this ionos expression remember this ionos expression leads to the inflammatory neurodegenerative condition in the mice brains and so they're suggesting that of course more research needs to be done but they are suggesting that treating the mice with myconazole demonstrates as strong anti-inflammatory response and leads to memory improving effects and overall it is an appropriate and effective way to control neural inflammation and hence prevent the progression of alzheimer's disease and the key take home here is that myconazole because it is a readily available drug that has already shown safety for topical use may easily be repositioned as a drug to be used for the treatment of alzheimer's disease i think that this is one of the most interesting and most important papers that i have read in 2020 i think considering the impact of mitochondrial dysfunction in humans not just in the respiratory system but the potential impact in neural inflammation the lot that we don't know about the impact of the environment and infection in general to cause adverse health symptoms in us means that publications like this that show that a anti-fungal drug can lead to memory preservation and improved memory response in the mice is really just brilliant research and it emphasizes yet again that there are there is a lot in the microbiological arena that we just don't understand we don't know how it impacts on us and therefore all of us need to be very mindful that these hidden microbes that we often don't even think about and take for granted have tremendous long-term impacts on us not just as a direct infection in any case my name's dr cameron jones i'll be back next week and thanks for watching listening to this podcast or tuning into this live stream it will be available on youtube later i'll look out for any comments i'll look forward to responding to those stay safe wherever you are and i'll see you next week bye for now

Channel: Dr Cameron Jones

Views: 841,233

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Id: KVAogG8m2iI

Length: 30min 58sec (1858 seconds)

Published: Sun Aug 16 2020