Getting to the heart of the matter: Precision therapies for age-related neurodegenerative diseases

[Music] welcome to the front row my name is jamie williamson i'm the executive vice president here at scripps research and today's special guest is professor jeff kelly who's going to tell us about neurodegeneration and drugs that can treat that jeff is one of our star scientists in the chemistry department here at scripps and jeff jeff got his phd in 1986 from university of north carolina he did a postdoc at the rockefeller university with tom kaiser and then he started his independent faculty position at texas a m university he joined scripps in 1997 in the chemistry department here and he's been here ever since and he's served in so many capacities he has been the the chair of the molecular medicine department he's been the dean of the graduate program he's been the vice president for academic affairs and he is currently our faculty represented representative on the board of trustees so jeff is a talented scientist and he's very generous with his time uh in in institutional activities jeff is an accomplished entrepreneur he's going to be telling you about the science in his lab today but he did start uh two different companies one is called foldrx that's uh the company that is now marketing to families and we'll learn more about that through his seminar and then also a company called proteostasis that's working on misfolding diseases and diseases such as cystic fibrosis and as a great run-up to this lecture uh jeff it was just a word the breakthrough prize and so this is in the life sciences now this is a very recent prize that was uh implemented by uh some serious entrepreneurs so sergey brin priscilla chan mark zuckerberg uh yuri milner and and mujiki these are the founders of companies such as google and facebook and 23 and me so this is a great honor for jeff and it the the basis of this honor is the subject of today's lecture so uh it's a real pleasure to welcome jeff kelly my friend and colleague take it away well first and foremost it's a privilege to be part of the front row i've enjoyed listening to this for a couple of years now what i'd like to do today is to try to explain how i do carefully executed basic research one can translate that into first in class therapies for aging associated neurodegenerative diseases so first let me introduce some common neurodegenerative diseases that feature dementia as a prominent symptom so dementia refers to the impaired ability to remember and think that's serious enough to impede the quality of daily life the neurodegenerative disease with dementia as a prominent symptom that affects the most individuals is clearly alzheimer's disease the economic burden is 300 billion dollars it is really hard on caregivers both financially and in terms of maintaining their health there's 50 million alzheimer's patients worldwide it's the fifth leading cause of death and we don't have profound drugs that modify disease progression the the second most common dementia is parkinson's disease that's also has a movement disorder component in most of the patients the economic cost is about 1 6 that of alzheimer's disease there's 10 million patients worldwide and it's the 14th leading cause of death the disease i'm going to talk a fair amount about today is arguably the third most prominent dementia that is the trans-thyroid and amyloid diseases these first present as a polyneuropathy followed by dementia or a cardiomyopathy the economic burn is at least 10 billion dollars to society and there's more than a million um worldwide so since the degradation of neurons is common to almost all of these disorders i'd like to first introduce the neuron so it's one of the human cells that's highly polarized and it's found both in the periphery and in the brain the cell comprises a so-called cell body or somas which houses the nucleus encompassing the genetic material and then there's a really long projection called an axon that can be as long as a meter or two and this axon ends in so-called axonal termini that closely approach the neighboring neuron shown here in blue so neurons as i'm sure you've heard conduct electrical signals and so the electrical signal progresses along the axon and when the termini are encountered the electrical signal causes neurotransmitters to be released which diffuse across the postsynaptic terminal engaging receptors that allows the electrical signal to to transit so neurodegenerative diseases can compromise the synapse they can compromise the axon and they can even destroy the cell body neurons like many tissues affected in degenerative diseases don't easily regenerate and so upon sustained insult or insults either as a consequence of genetics or an environmental illness insult such as the pesticides that can cause parkinson's disease a number of neurons can die generally associated with aging for reasons that i'll explain in a minute and the problem with this is that the brain is the neurons are connected to many many other neurons and so there's a very complicated communication pathway that allows the brain to normally function and when neurons start to die and drop out of this communication system that leads to dementia behavioral deficits and and other attributes of neurodegenerative diseases now it turns out that several organ systems are compromised in neurodegenerative diseases so for example in parkinson's disease the gastrointestinal tract in most patients are affected a decade before you see central nervous system pathology and in alzheimer's disease it's now becoming recognized that there are cardiac deficiencies in gi deficiencies that present in parallel with the central nervous system pathology and i'll talk a little bit about the other organ systems that are involved in the trans-thyrotin amyloid diseases as well the most important message today is that neurodegenerative diseases are disorders of protein shape so proteins normally are spherical they're two to three nanometers in diameter and remember a nanometer is one billionth of a meter so these are really small you can't see them with the negative eye in contrast the abnormal protein shapes that are linked to these diseases are much larger a couple of nanometers wide by as as many as 3 000 nanometers long so to put this in perspective if you just change the scale here and say this is two to three miles right this is the size of a really small town or or um hamlet in contrast these abnormal shapes can span the east coast to the west coast of the united states so they're very much bigger and i'll talk about how these abnormal shapes lead to neurodegeneration in the following slides but first i'd like to introduce how proteins adopt their normal shapes and this constitutes cellular protein folding so the the central dogma of biology which is common to all living organisms is that dna is transcribed into rna and rna is translated into proteins so for the purpose of of today's presentation proteins are best thought of as an unlatched pearl necklace composed of 20 different types of pearls these in fact amino acids that are connected in to one another to make proteins and these pearls or amino acids differ with respect to their chemical properties so in the following slide i will represent each amino acid as a small circle with a letter in it the letter is the single amino acid code for a an amino acid you needn't be concerned about that only to the extent that the different letters represent amino acids with different chemical properties now the reason that proteins adopt shapes is that each amino acid has an affinity for a subset of the other amino acids when they're incorporated into a protein and this forces proteins to adopt shapes by a process known as protein folding that generally is spontaneous and the nobel prize was in fact awarded to anfinsen for demonstrating the spontaneity of this process so if you think about this as being our unlatched pearl necklace wherein each amino acid is depicted as a circle and the different chemical subtypes are indicated by different letters we can envision because some amino acids like other amino acids like to be close and they can stabilize structures through chemical interactions these proteins start to fold up and eventually they adopt a well-defined folded structure now it turns out that this process is about you know 50 to 70 percent efficient depend on how depending on how complicated the protein is so that means the other you know 30 to 50 percent of the flux goes to misassembled structures and so these amino acids can satisfy their desire to interact chemically with another residue either through uh intramolecular or self-interaction or these partially structured proteins can interact with one another in a bimolecular fashion or an intermolecular fashion so if i trace out one of the protein chains it's here and these amino acids can satisfy their desire to be next to others by making these really long structures that i showed in the previous slide that can span from the east coast to the west coast on a kind of a geographic length scale so this is an abnormal shape this is an abnormal shape and this is an abnormal shape as proteins go so since protein folding is not entirely efficient and you make these misassembled abnormal protein shapes biology has evolved such that there are very efficient degradation systems within cells that degrade these aberrant shapes and they do so very efficiently so that when we're young we have very low concentrations of these aberrant shapes that are linked to neurodegeneration through mechanisms i'll describe shortly now we all know that these diseases are aging associated or the risk of getting them increases as we age and the main reason for that is that these cellular degradation processes decrease in efficiency with aging thus these structures start to build up up after age 65 or so and we start to accumulate these structures that can harm tissues that don't easily regenerate like the nervous system so um i just want to say this again here so cellular degradation competes with misfolding and misassembly cellular degradation becomes less efficient as we age and hence the aging risk for these diseases and abnormally shape proteins accumulate within the cells in about half of the neurodegenerative diseases so really good example of intracellular accumulation is alpha synuclein and parkinson's disease in tau which which is responsible for the later stages of alzheimer's disease so one of the things that we're doing in the lab currently in collaboration with kristin johnson and arnab chatterjee at caliber our not for profit drug institute is to come up with um small molecules that enhance intracellular protein degradation and function in aged individuals and we're also doing this in partnership with stuart lipton and other faculty members at scripps in our newly formed neurodegenerative diseases new medicine center so the way this so-called autophagy system works is that you have a double membrane structure that wraps around um various structures that lead to these diseases and degrades them and when it degrades proteins it regenerates the amino acids and so that's that's a really nice system and someday we hope soon we hope to test these um small molecules in clinical trials now i mentioned that half of the neurodegenerative diseases result from intracellular misfolding the other half result from the fact that about a third of the proteins are sent outside of the cell and the inability to maintain normal shapes in the extracellular space causes major neurodegenerative diseases so in order for a protein to be sent outside of the cell it has to have had adopted its proper shape that's just the way the quality control machinery in the cell works so it's all about maintaining the normal shapes of protein in the extracellular space to prevent these neurodegenerative diseases so what comes outside of the cell is none of these shapes that i'm tracing out with my laser pointer that are abnormal the only thing that comes out is the normally shaped protein but depending on the stability these normally shaped proteins can become partially folded and misshapen and they can satisfy their desire to interact with other amino acids by misassembling and to further complicate things these various shapes that are formed can undergo so-called shape conversion into things like amyloid fibrils which are very long and well structured and in fact have been implicated as causes of of these degenerative disorders so the the idea is that the the structural biologists have characterized many of these abnormal structures and what many companies have done here to for to try to ameliorate dirt neurodegenerative diseases is to clear one or a couple of these structures in contrast what we've decided to do as a therapeutic strategy is to stabilize the the normally folded structure or maintain the shape of the normal protein as it come out as it comes out and prevent newly synthesized proteins from coming apart and forming all of these shapes that are linked to neurodegeneration by a process i'm going to explain uh in just a few minutes so the key question of course is then why do these abnormally shape proteins um cause neurodegeneration or lead to neurodegenerative diseases so let me first say that normally shape proteins function as a consequence of their shape so this is a a protein that's called the gpcr it is um representative of how proteins work so typically you have a partner for a protein that binds and if you look down here you can see that upon finding of say a peptide trigger for a given biological event that changes the shape of the protein that allows it now to interact with the blue protein and that perhaps causes transcription or something in the cell that is important for biological function so normal protein shapes elicit the work of proteins so thus abnormal shapes of proteins confer abnormal functions and so as i mentioned the structural biologists have characterized all these abnormal shapes over the years and many labs have shown that these various shapes perform aberrant signaling within the cell that a very signaling from outside the cell the genes that are expressed determine cell type and these structures really screw up this ability to have translational fidelity including many other functions and the idea is that these abnormal functions when expressed over multiple years start to compromise neuronal function and they ultimately um kill the neuron so our strategy is very simple in principle that is as a protein is secreted from the cell we want a very rapidly intercept it with this green structure namely a small molecule that is capable of stabilizing the normally folded or normally shaped protein and keeping it in this shape as opposed to letting shape changes occur that drive neurodegeneration so i'd like to outline what we've done in this context in the scope of the trans-thyrotin amyloid diseases so these are diseases that first affect the peripheral and autonomic nervous system and later cause dementia in the central nervous system some people exhibit cardiac symptoms before they show um neuropathy if in fact they ever show neuropathy so you see um differences in disease presentation that seem to be based on which abnormal protein shapes are present so the normal shape of trans thyroid is shown in this red box and it can bind a lots of different things in the blood plasma but the form of the protein that we're interested in today is the one with no ligands but trans-thyrotin is a so-called tetramer it's comprised of four identical monomeric proteins that then come together to make this tetramer and it turns out that many proteins in various organisms are oligomeric and they function as oligomers now the human genetic evidence that was in place before we got interested in these diseases suggested that the inability to maintain the normal shape of transthyratin was what led to all of these aberrant shapes forming and neurodegeneration as a consequence we performed a decade of of really careful research to understand the pathway by which this protein shape changes that lead to neurodegeneration so as i mentioned the cell secretes the normally shaped protein and one of our major contributions to the field was to show that the normally shaped protein cannot misassemble into shapes that cause neurodegeneration instead this tetrameric protein has to dissociate in what turns out to be the slowest step associated with forming these map and proteins or a process that's rate limiting for aggregation so first you form dimers and then you form a monomer that has a normal shape and when you form a misshapen monomer then the protein can misassemble very fast it's you a spectrum of non-native structures that are the putative cause of these degenerative disorders so what we decided to do was fashion small molecules so as to be able to bind to and maintain the structure of the secreted form of the protein that has a normal shape and so the idea is we want to make this structure really stable by virtue of drug binding and this would then prevent the formation of all these other shapes that have been linked to various degenerative phenotypes be it neurodegeneration or cardiomyopathy and we suggested that instead of guessing which form of these proteins is the main driver for thought for pathology a conservative strategy would be to just block the whole process and that's in fact what we did so a key player in all this is evan powers so when he was a a postdoctoral fellow in my lab his job was to look at the native shape of transthyrotin and fashion all molecules that beautifully complemented the two small molecule binding sites that this protein was known to have which incidentally are unoccupied in us they're occupied in rats and mice and lower animals but not in humans so we took full advantage of that using structure based design to make beautifully complementary drugs to stabilize and maintain the normal shape of trans thyroid so now fast forwarding a few years to the human clinical trial what the neurologists measure in these patients is sensation in the lower limbs so the the ankles and the toes and in the lower legs muscle strength limb reflexes and then they come up with this so-called neurologic impairment score and if you're a patient you definitely don't want the score to go up because that means you're worsening so this is the results of the placebo-controlled clinical trial the individuals who were giving our drug which has the name to families or or vindimax had a much lower rate of progression than those individuals that were on placebo and what we noted in the trial was that about 70 of those individuals who had neurodegeneration who were given to feminists were stable or improved by the drug but if you were in the placebo group and so you had to wait 18 months to start treatment with the feminists now instead of getting a 70 of the population to respond now it's less than 50 percent and this is the general rule in neurodegenerative diseases that it's really important to diagnose these diseases early and to get the patients on therapy and as we become much better at diagnosing these diseases you could imagine using a very safe medication like to feminist even as a means of preventing these disorders so this is the slide that um was generated by uh clinical investigators in portugal this is called a kaplan-meier analysis and this represents deaths that occur in individuals with neuropathy so every time this curve goes down it's a patient dying and so obviously you want to flatten the curve as much as possible with the medication versus the situation that occurs in the untreated patient group um and you can see that to families really has a profound effect on stabilizing the health of these individuals and preventing a mortality so i should just be clear here that the the clinical data go out to about here and the rest of this curve is based on very sophisticated mathematics and statistics and i hope they're right but we shall see but clearly we have a huge difference in the part of the curve suggesting that tefamidus prolongs both health span and lifespan in these individuals by slowing the progression of neurodegeneration so mention in some patients this degenerative disorder first presents as a cardiopathy and you can see here well you may not be able to see but i my eye has reps looked at a lot more of these hearts than you have these walls in the heart are about three times thicker than they're supposed to be and that thickness is largely caused by how much non-native protein has deposited within the heart and so um these are really serious degenerative diseases that ultimately cause heart failure as a consequence of abnormally shaped and misassembled trans-thyrotin formation so matt maurer who's a very sophisticated clinician worked with our colleagues at pfizer who bought foldarx the company that the late sulien quest and i started to commercialize this small molecule that we discovered in the lab at scripps and matt came up with this really sophisticated trial and in the end um we showed a significant reduction in the combination of of all-cause death and the frequency of heart disease associated hospitalizations so this is the data that matt published from his own lab with really quite early stage cardiomyopathy patients and when you do a big trial the data is never as good because you have people who are late stage you have all kinds of different ethnic backgrounds and so on but we were very pleased to see that we saw a nice protection of those individuals who were on to families versus the placebo group but it takes a little bit of time to manifest and again if you ca early that is in new york class 1 heart failure you get a reduction in the risk of death of about 65 if you let them progress to class 2 the protection from the drug goes down to just under 40 so again critically important to get these patients on drug early and if you just look at say performance in a six minute walk test the distance that patients can cover in six minutes declines over time but it declines much more slowly when patients are on to families versus placebo so um again further evidence that in fact this drug is is working in cardiomyopathy patients now cecilia monterio who is a very um talented neurologist came to my lab to do a phd in chemical biology and one of the things that she did was to look very carefully at a different set of patients that is individuals who are getting to feminists commercially and what she found was that about 70 of the patients respond to defamitous in in the sense that their neurologic impairment score doesn't go up over five years but but about 30 percent of the patients behave like they're not on drug at all and of course this was very disturbing to us at first we thought well maybe these patients are metabolizing the drug differently or something but in fact these patients have the same protein protection as these patients and um i'll i'll come back um in an a in a slide from now and show you why that might be the case so we thought a lot about this and it turns out there's emerging evidence that immune cell overreaction by these abnormal shapes laden degenerative diseases can become a major driver of neurodegeneration and this has been explored quite extensively in alzheimer's disease and most people feel that this is the reason why alzheimer's patients don't respond as well to reducing the abnormal shapes because not only are the abnormal shapes driving the disease also over activation of immune cells are driving the disease so early on these immune cells are very beneficial later on they do things like eat synapses and that's really bad obviously since neuronal function depends on synapses so these cells are called microglia and astrocytes they support the brain and they take care of garbage and when proteins start to form these abnormal shapes in the extracellular space this activates these microglia and astrocytes and they start taking these abnormal shapes in to their lysosomes and they degrade them and that's a good thing but over time these um the process of aggregation starts to overwhelm the ability of these cells to do housekeeping and they become hyper activated and the problem then is that you end up with so-called dystrophic neurites and that's in part because these glial cells and astrocytes themselves start to eat the neurons as well as what's in the extracellular space causing their death and as i mentioned once neurons start to drop out of the brain then the communication in the brain is faulty dementia ensues and this is really problematic so lots of labs now are trying to understand this process and develop drugs not only to treat the misshapen proteins and prevent them from forming but also to keep these cells under control so that they do good but they don't um become over-activated and do bad things so i hope what i've done today is to provide you a broad overview about these diseases and i want to tell you that my um colleague supriya shreverson is giving uh the next um front row lecture entitled unlocking new insights in the brain gut communication metabolism and longevity supriya is a fantastic scientist and speaker and i'm sure you'll enjoy her lecture um i want to thank you and i'll i'm closed by just saying that over a hundred people worked on this project and um these are a few that made um very significant contributions but there are many more without them i wouldn't have very much to talk about today thanks thanks jeff terrific lecture uh everyone is virtually clapping at this point and i i i think uh uh it's your lecture has generated a lot of interest there's been some spirited discussions and i'd like to to in the chat uh i'd like to ask a couple of questions to follow up um so you touched at the end on on autoimmunity and and that that sort of brings up the question about uh you know viruses and vaccines and covid and other kinds of viruses and how does that intersect with neurodegeneration and specifically these protein folding diseases so well maybe i shouldn't go back to the slide so you saw the images of these microglial cells and in the init initial facets of neurodegenerative disease they do very good things so it turns out that these cells can also be activated by infectious diseases and viral infections can in fact negatively affect the brain they may do so by helping get these microglial cells into a bad state that is these hyperactivated states and diseases like hiv and other viral diseases have their own neurodegenerative components so um that's what i would say yes it's not good to get these viruses not only for the acute effect but the long-term effects can be devastating so for example my colleague stuart lipton told me that individuals who survived the 1918 flu a subset of them decades later had a parkinson's like disease and so these viruses can do bad things long term as well as short term so there there was a lot of questions that kind of center on various aspects of what you'd call proteostasis you know the balance between production and degradation of the protein as a normal function and so so is accumulated of the misfolded protein is that due to an increase in the rate of misfolding or or is it a deficit of the lysosomes and and how do those two factors play into this this partitioning in these diseases so i i think the evidence that's emerged thus far suggests that the efficiency of the degradation processes wane with aging and that waning leads to the build up of these abnormal shapes now it could be that um aging has something to do with increasing the efficiency of protein misassembly and forming these abnormal shapes but i would say that evidence isn't as strong there okay so you know so why why do cells throw out proteins in the first place why are we constantly degrading these proteins and you know it makes sense to degrade the bad ones but what's what is the kind of normal housekeeping turnover why is that why is this happening so i i think most scientists are humbled by how complicated some of these processes are and the fact that these proteins can even fold it all is a whole field onto itself so the fact that protein folding is inefficient isn't a surprise to that group and so you know life um solutions derived from evolution are are often far from perfect and so probably the degradation system in part evolved well you have to turn over proteins eventually but also in part evolve because um folding just is never that efficient uh so so tefamidus targets transthyrotin which which has an endogenous ligand and and so what happens to the normal function of transferrin when you've got defamatis in play does it compete and you know is there some other downstream bad effect of the drug yeah it's a great question of course the fda was very worried about this um and so it it turns out though that the trans-thyroid and protein in humans is a minor player with regard to thyroid hormone binding and transport it it probably binds less than one percent in the periphery and five percent in the brain so we had to demonstrate to the regulatory agencies that the you know the distribution in the periphery in the brain didn't change and that turns out to be true so these binding sites are are again a kind of a relic of evolution in humans there are much higher affinity proteins that carry around thyroid hormone but in lower animals like rodents trans-thyrotin is the main player okay um so here's this is kind of a basic protein folding question so you talked about forming the right shape and forming the wrong shape is in general is is forming the right shape is that the most stable structure generally speaking well it can be but when you when you form these structures that on a city scale span from you know the west coast to the east coast those structures are incredibly stable and though that's the amyloid one of those is an amyloid structure right in many companies have gone after the amyloid structure i think we still don't know how pathogenic that actually is but those are probably incredibly stable fortunately for us the rate at which they form is really slow so you really have to have screwed up degradation to get those to form to any appreciable extent right so so this is another kind of version of the proteostasis question so so why does misfolding get worse with age is is it the misfolding is getting worse or is it just the accumulation of the misfolded shape yeah it's a it's a great question it's so you know a lot of accumulated damage occurs with aging right i mean what we recovered from when we are 20 is a little harder to cover from when we're 60 or 70 or 80. so the machines that do things like acidify the lysosome which is critical for degrading proteins don't work as well when we get older in part because they're you know there's some damage there in part because the membrane's not quite what it was and so on so i i you know there and then there are a lot of epigenetic changes which which means that the proteins that are expressed early in life aren't exactly expressed in the same proportion later in life those are called epigenetic changes we don't really fully appreciate why that happens but it can have some negative effects for example the processes of activating these degradation pathways just don't work as well because of epigenetics that probably protects us from cancer but puts us at risk for neurodegenerative diseases well jeff we got we have a lot of questions pouring in it's it's there's there's been a tremendous interest but uh you know i i think i think we should kind of wrap things up a little bit i do have a couple of more general questions so first of all i want the audience to really appreciate this is not an advertisement for but what it is an advertisement for is the power of basic research to provide the the basis for creating a new medicine and you know i think there's on the order of let's say 20 to 50 new drugs approved by the fda in any given year and and these are all the basis of you know decades-long programs uh there's thousands of companies there's hundreds of thousands of scientists and i have to say jeff is kind of a unicorn he is one of the people that made it all the way from bench into patience and and it's really it's really a remarkable story so so one of the kind of general questions i i want to ask you is what was the aha moment for tofaminus i mean i know your lab was working on basic studies of protein folding and and you know at some point you started playing around with ligands that bound to them now did you set out to make a drug were you looking at basic physical chemistry of ligands binding to proteins what was the aha moment where you kind of said oh man this might actually work so we we were in fact making chemicals to stabilize trans-thyrotin it was um i would say a modest effort in the lab and we were hopeful that that might work the aha moment came when a woman in portugal teresa calejo very distinguished md phd found individuals in large families that had a mutation that predisposed in this disease that weren't getting it and when we translated that genetic observation into biochemistry with her health what we found is that the protection mechanism to keep the or maintain the native shape was strictly analogous to what we were trying to do pharmacologically and that supercharged our efforts because we knew it should work in humans then now it was done in such a way that you couldn't really convert what mother nature did to protect these people into a drug or at least it wasn't so obvious then how to do it right and you know when was that that that was probably in uh yeah early 2000 i think yeah so pair hammerstrom was the postdoc that did that work he's now a professor in sweden so you know folks it's just it this is a decades-long effort and it worked out uh and scripps has got a pretty deep bench of people working on some pretty exciting uh medicines for the future so jeff let me just ask one question in closing so uh how did you figure out that you wanted to be a scientist what you know what you know well what was the what was the process how did you you know go into science and and when did you decide you wanted to be a professor i i think the short answer is by accident which is kind of defines my life to a certain degree but you know you know when i was a kid i i really loved to try to understand how mechanical things worked and so i i destroyed many things around the house that i probably shouldn't have taken apart but i did learn how some of them work and it really i didn't i really didn't even appreciate when i was a kid beyond of course chemistry that there was this microscopic world of mechanical devices right and it was really organic chemistry professor at suny fredonia where i went as an undergrad that made me aware of the opportunities and fascination with this and i i got excited never turned back i guess and you became a protein mechanic yeah indeed i just want to uh i just want to show a little blast from the past so this is this is a group picture of some of the sorrel scholars from this is about 1992. uh jeff kelly is third from left um and uh that's actually me second from right and raise our colleague raza gadiri's on the far right uh we had an annual meeting and we were all the young turks uh of science at that time and uh i would say well jeff had more hair and i had more hair too [Laughter] but i've known jeff for a long time and uh it's been it's just been great to have him as a colleague for for almost 30 years now so um i i thank you all for coming to the front row i remind you that we have uh supriya srinivasan who will give the lecture it's wednesday october 13th it's been a real pleasure so join me in a virtual thank you to jeff for for a really inspiring presentation uh hope to see you back at the front row bye bye folks [Music] you

Channel: Scripps Research

Views: 739

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Keywords: neurodegenerative diseases, parkinsons, alzheimers, jeff kelly, scripps research, science, lecture, alzheimer treatment, parkinsons treatment

Id: ynLKHxRtx-4

Length: 51min 25sec (3085 seconds)

Published: Wed Sep 15 2021