Secrets to Alzheimer's, ALS and Parkinson's Disease: Dr. Paul Alan Cox at TEDxJacksonHole

[Music] in 2006 we chose Jackson Hole for a very interesting endeavor I'd spent last 30 years or so living in small villages working in drug discovery programs fortunately I was blessed with success we discovered a new aids drug drugs for inflammation immuno stimulation but I wanted to go for a very specific disease called ALS I'm just interested how many of you have had a friend or acquaintance here that suffered from ALS or Lou Gehrig's disease good heavens that's a large percentage of the audience the pharmaceutical industry and I have a lot of respect I've worked with most of the major players but they take too long it costs right now about 800 million dollars to 1 billion dollars to get a new drug on market that takes 10 to 14 years ALS patients don't have that sort of time once you're diagnosed on average you have two years to death so we decided to create a virtual pharmaceutical firm by cherry-picked the top scientists we got 27 universities around the world from Tokyo to Stockholm to work with us we set up a first-rate laboratory I like to tell people we have the best amino acid laboratory within two blocks of the Jackson town square and I want to tell you a little bit about our success and what we've been doing I want to start you off a Grand Prismatic spring in Yellowstone National Park one of my favorite places what's interesting although the Yellowstone Basin is geologically recent those residents in that that cause the colors are very ancient these are cyanobacteria photosynthetic bacteria in this case the yellow pigments on the screen are caused by the genus form idiom and Senate caucus you know these are probably more familiar to you as mats or scum that you see on low reservoirs or golf hole water traps we have on the top from our laboratory a light microscopy photo of cyanobacteria fluorescent photo they're fascinating organisms in fact it's believed they're the oldest organisms on planet Earth we have fossil record going back 3.5 billion years of continuous occupancy of cyanobacteria on planet Earth here they create giant blooms this is a boat in the baltic ocean going through a mass population of cyanobacteria here's a satellite photograph the entire Baltic you can see that some of these blooms measure thousands of kilometers so let me tell you a few quick things to remember about cyanobacteria first of all they're the oldest organisms on planet Earth this means that they created the oxygen atmosphere of the earth prior to the advent of these photosynthetic organisms this would have been a lethal environment because of ultraviolet radiation they create and continue to be the major sink for carbon on this planet to nano planck in general so small you have to have a microscope to see 'm have the greatest capacity for absorbing carbon dioxide in the world's oceans and all of the rainforests combined they are found everywhere from the hot pots of yellowstone to the antarctic to the gulf regions of the persian gulf they're everywhere and what we're very interested here that our institute is that they produce toxins this is the toxin beta methyl amine o l alanine or BMAA the right part of the structure is the common amino acid alanine but when cyanobacteria produce it they add an extra nitrogen group and a methyl group onto it thereby making it neurotoxic we've discovered in our research that almost all cyanobacteria around the world produced this toxin so we also found that they live inside the roots of the cycad trees and so I want to take you from Jackson Hole to the middle of the Pacific Ocean where we've been doing work in the islands of Guam here's a root of the tree that I've cut in with my Swiss Army knife you can see that green photosynthetic layer our cyanobacteria we brought these back to our laboratory cultured them and found that they produce this neurotoxin BMAA so what you might ask well we got interested because we found that these are produced in these roots that are aerial so they can get photosynthesis and the indigenous people have gone on the Chamorro people have figured out how to take the seeds of the tree take the kernel of the tree or the gametophyte and make our out of it we discovered that this flower is rich in the neurotoxin and we started wondering if this could account for the devastating form of ALS that this village has we've made mobile expeditions of the village 25% of the people are dying of this disease to put that in perspective one out of 350 Americans dies of ALS imagine a village where a quarter of every adult death is attributed this what's even more interesting is that these people like this individual on the screen time we have typical als symptoms others have symptoms of Alzheimer's with cognitive loss others show Parkinson's tremors some poor individuals have all three form of symptom ologies all at once could this neurotoxin be linked to this disease we also discovered but large bats called flying foxes eat the cycad seeds and accumulate the toxin in their tissues at ten thousandfold times the bacteria produce so when the people eat these bats and they love to eat them they eat the the the head the wings the fur they love them so much that they extincted one species and put the other on the endangered species list the only remaining bats are on Anderson Air Force Base a nuclear weapons base I've recorded two interviews with tomorrow's who have taken their guns gone under the b-1 bomber being around the nuclear weapons bunker shot a bat and repeated the process to get out of there suggesting to my mind that either these people have an insatiable appetite for flying foxes or that our much vaunted homeland security is still not up to snuff so the hypothesis that we developed is that these bacterial cyanobacteria produced this toxin BMAA it accumulates in the trees gets into the people and kills them but since cyanobacteria occur everywhere could that be what's happening to ALS patients here in the mainland our colleagues at Dartmouth University or inter consortium dr. Elijah's tamil in the neurology department there started mapping als patient radio resonances in New England and what they found was totally stunning to me that the als patient residents in New England tend to cluster around lakes and streams that are polluted and have sign of bacterial blooms but not around pristine waters in fact the Dartmouth team estimates that if you live next to one of these streams your risk of getting ALS goes up 25 fold now what's interesting about ALS Alzheimer's and Parkinson's that their tangle diseases they're caused by miss folded and tangled proteins could be maa play a role in tangling these proteins when I lived here my dad was a ranger in the park this was Christmas I got a slinky turns out a slinky is actually a very accurate model of a neuro protein 20 different amino acids and different sequences are linked unfortunately this is typically what would happen to my slinky in Moose Wyoming after only about two weeks could be maa cause a perfectly formed neural protein to generate a tangle characteristic of these disease let me see what happens DNA has the instructions to assemble neural proteins here we have serine coming in to the ribosome each of the 20 amino acids has a different tRNA that brings it in what we discovered with our colleagues Ken Rogers and Rachel Dunlop at Sydney Technical University is that if BMA is present it actually grabs the tRNA for serine and knocks it off and kinks the slinky and causes human proteins to miss fold when we announced this discovery last year at the internationally les Congress you could heard a pin drop because we think just by chance we've stumbled on a major mechanism for protein misfolding so our hypothesis is this you're exposed to BMA it crosses the blood-brain barrier it missed charges this tRNA it gets incorporated in the protein cause of the protein to miss fold this causes the proteins get sticky and aggregate meanwhile yet directly is toxic to motor neurons and causes ALS but even more important was a discovery that just took our breath away we discovered with our Australian colleagues that if we add excess serine to human cell cultures that we can stop protein miss folding we can stop the tangles and we can stop miss insertion of BMAA we discovered that the dietary amino acid el serine blocks BMA from inserting the proteins is it possible that a common dietary substance could prevent or possibly even treat ALS we are now moving as fast as we can on this because again the patients don't have time and so we are beginning this year trials of el searing 420 ALS patients our previous drug is already in phase 2 fda-approved trials this will be in the phase 1 fda-approved trials there's nothing I'd be happier with than to have a new treatment for the serious disease walk out of this town I want to thank my colleagues aren't so honored to work with dr. Sandra Banach dr. James Metcalf Sam the smartest people I know and all 27 universities around the world that's helped us thank you so much for welcoming here to TEDx and [Applause]

Channel: TEDx Talks

Views: 164,574

Keywords: TEDxJacksonHole, ALS, Parkinson's Disease, Science, ted x, English, ted talks, tedx talk, ted talk, tedx, United States (Country), ted, Medicine, tedx talks

Id: 7jWi6WQQ9wo

Length: 10min 53sec (653 seconds)

Published: Wed Oct 31 2012