Rare diseases research, challenges and firsthand accounts

[Music] [Music] good morning and welcome to Washington Post Live I'm Dan Diamond a national health reporter here at the post post today is rare disease day and I'm pleased to be joined by the commissioner of the Food and Drug Administration Dr Robert caleff to discuss rare diseases artificial intelligence and more Dr caleff welcome to post live thanks Dan good to be with you let's start by reviewing the rare disease landscape and even defining some of the key terms here so a rare disease accordi

ng to FDA affects fewer than 200,000 Americans there are perhaps 10,000 rare diseases across the United States more than 30 million Americans affected by a rare disease but about 5% of rare diseases have an FDA approved treatment doctor when you think about those numbers what what does that say to you what does success look like when it comes to combating rare disease well I think you can look at it from two Dimensions one is just the number of diseases and the changes in science there's so much

that we can do we need to tackle in essence one disease at the time and find a treatment that's effective or even a cure perhaps but of course for an individual family one of the 10,000 uh PE uh uh diseases would be very concerned um about any delay in getting an effective treatment available uh available so we're uh energized and excited by the side science uh feel the pressure and think the pressure is appropriate but also given our mission we need to be careful with the science to make sure

we do it right do you have an achievable goal in mind when it comes to rare disease could 15% of rare diseases have an FDA approved treatment in the near future then I I feel like it's not probably not right for us to set that Target because um it's good to think of the FDA I think as a referee in other words uh um we evaluate um data that people bring to us in that all saying God We Trust all others must bring data uh the development programs themselves are done by companies um the basic scienc

e is done by the ni um and so ultimately it's an ecosystem uh where we all need to work together and rather than set a goal I would say we need to say we've got to be making measurable progress and we should see an acceleration of that progress not just a linear Trend but more of an exponential Trend because of the beauty of the science now as lending itself to platforms that might be useful across a whole variety of diseases as a referee here when you look at the companies working on rare disea

se treatments what have you found to be the most effective ways of motivating more progress doctor well um it's it is very important for the FDA to be in tiptop shape here because because uh companies are funded by investors who are looking for return on Capital and so they have to have a case that they'll be able to get a product through the FDA if it's good now having said that and assuming that we are highly motivated to get better and better at the FDA and how we function in order for the co

mpanies to succeed they have to have uh First Rate science they have to develop assays that are predictable and measure measurable they have to have a technology which is scalable um and high quality and very importantly particularly in rare disease they need to work with the rare disease patient groups since these uh people are scattered across the country and really across the world and there aren't large numbers in any single place it means that we need groups of patients to band together and

work with the companies always keeping everything um uh in line in terms of the science because most things that we try are not going to work we already know that but there will be enough that work now that tremendous progress can be made it's got to be done officially which means an ecosystem that works together you mentioned the patient groups I'd like to come back to that in a moment but first talking about the ecosystem you've obviously spoken about the fda's role the companies working here

I'd like to think about other parts of government for instance Congress Congress 40 years ago enacted the orphan Drug Act which was intended to Spur more development uh of rare disease treatment is there more work that Congress needs to do now doctor to give your agency tools to combat rare diseases this may be one one of the rare times where you'll hear me say that we don't need that much from Congress at this point we can always tweak the system but we have tremendous Tools in our disposal uh

as it relates to FDA now there are things that are outside of the fda's pr primary swim lanee if you will where um I think as a society we're going to have to think carefully about what to do for example if you think about 10,000 rare diseases and the patients that are involved as these clinical trials get done and the care that they need this is mostly going to need to happen in academic medical centers that have the specialty expertise to provide the care that's needed and that gets directly

into the NIH and the professional groups and the academic Health Systems and let's assume that um we had just for fun let's say we had a th000 cures on the horizon right now there's not a model that I know of that'll actually fund the R&D from the private sector at the level that's going to be needed so that's going to need some work then let's assume that uh all thousand worked how would Society pay for the treatment right now the treatment's expensive now these latter things are not primarily

in our lane and it might be a place where Congress will need to act but first we got to come up with the ideas together and so there's a lot of good discussion going on and this rare disease week that we're in this week I expect there'll be some pretty exciting ideas I did want to ask one followup on Congress we got a audience question here that I'd like to read from Jessica in Virginia she asks can you speak to the proposed promising Pathways act sponsored by Senator Braun to create a quote con

ditional approval pathway for rare disease drugs and whether that would be a useful tool for FDA commissioner well Dan as you know we're um not allowed to speak uh in detail about legislation that's in a proposal phase and I'd say it's evolving I'm on record as saying we need to be creative about um our approach and do what's going to be most effective whether a you know conditional approval it's a technical teal term um this probably requires too much detail to get into in this discussion let's

just say we're we're working with Senator Bron's team and the FDA team our job is to give technical assistance in the vein the analogy of referee that I use the rule book is written by congress not by the FDA our job is to interpret the rules and apply them um on the field the field is the medical product development Arena so we're open and interested in the discussion want to be as creative as we can but we also really want to make sure that we don't start putting products out there that are i

neffective or dangerous uh without the appropriate uh human clinical research being done you've mention the broader questions for society in terms of paying for these treatments the cost that is on the mind of our readers as well I'd like to take another uh reader question from Leonard in Massachusetts who asks Medicaid ations developed to treat rare diseases tend to be extraordinarily expensive if drugs become unaffordable it is as if they do not exist at all this becomes more problematic as mo

re of these drugs are developed what can be done to keep the prices for these drugs low enough to afford Dr kalea well Dan uh first of all let me just say this is outside of fda's Lane you know that we're prohibited actually by law from considering cost in our decisions at the FDA I am um a principal uh at the table at Health and Human Services where these issues get discussed so given that it's not in my Lane I would just say um we are going to need creative approaches to um paying for these th

erapies for example um it's understandable the cost up front is going to be high but for example with Gene editing it may be you only need to get treated once and you got a treatment so there are ideas on the table like like um amortizing the cost over time rather than paying for it all up front but none of these are in statute yet um there are many potential ideas and we're just going to have to be uh creative in how we handle it you have invoked the word creative quite a few times already with

me I know this has come up before when you've talked about the creative approaches needed to combat rare diseases are there creative approaches that we haven't talked about yet you'd like to expand upon well I mean first of all it's so exciting the the way science has come you mentioned the um orphan Drug Act but right along with that I think comes a Human Genome Project where um based on the ideas that some people had our country made a big betat through the NIH um and also the private sector

invested in um understanding the human genome now here we are we can actually look at a specific Gene edit it sniff out the Gen Gene put in a new one there are other ways of modifying Gene function but we don't know the long-term effects of these so one example of a creative thing we're going to need to do is figure out how to follow people over the course of 20 30 40 years after treatment because we don't know what the long-term risks and benefits are going to be for sure and our approval Pathw

ays will give us a moment in time where it's reasonably likely that the benefit will far out outweigh risk but we got to develop methods of measuring that and getting the follow-up studies done somebody like me that's been a clinician and an electronic health records person there is a lot of room for creativity in how we use data particularly with uh the way Computing is changing now with AI and Quantum Computing on the horizon I'd like to talk a bit about patient groups or as some might think c

itizen scientists the folks who are activated here around these diseases many patients with we diseases their families have had to become citizen scientists advocating for their own treatment or the development of treatments doctor how do you see these folks driving medical treatment today well you know my career as a cardiologist working in intensive care units the intense interaction that occurs when someone is critically ill or has a threat of being critically ill you know it's hard to I thin

k we all have a feeling for it it's hard to describe unless you're in the middle of it I think the thing that has really changed and is taken to heart very much by the FDA and I think most people now in the medical ecosystem is that no one knows more about the problems of the diseases they have or the issues that are involved things that need to be solved through Therapeutics no one knows more than the people who have the diseases their families and those who care for them and what's also become

clear and I think this goes back to the days of HIV um I happen to be an intern in San Francisco in 1978 we had patients with HIV we didn't know what it was uh development was slow in the view of the patients they banded together and became part of the solution it went from being angry at the system to taking a view where you're angry to the extent that you want there to be impatience but you band together to get the studies done because what the HIV Community Learned was that a lot of our best

ideas don't work and you don't want to be promulgated treatments out of desperation that don't work which means that if you band together get the studies done efficiently make sure that um if there is a positive study that the treatment uh is made available in a way that's fair that is a tremendous value that patient apoy groups um can play and it's especially important in rare disease as I said because people are scattered all over the place and they need to form networks of people who work to

gether toward this end you know I would point to cystic fibrosis and type 1 diabetes as cases where things have moved along at lightning speed compared to most other diseases because the patient groups got highly organized my observation at FDA is as a public health agency it's our responsibility to help people band together and it it was so obvious to me that groups that were highly effective did better because it attracted investment it attracted new ideas it attracted clinicians and scientist

s but it's not fair if you happen to be a patient with a disease it's not very effective for axy I think it's our responsibility to help make that happen well let's talk about one of those patients there is an oped in the Wall Street Journal this week by Judy ster a former senior H Shake Jess official criticizing the FDA for being too slow to help save her son from a rare disease she writes though I know firsthand that the FD civil servants are committed to their mission the agency's onerous bur

eaucracy impedes access to possible treatments with no meaningful gain for patients and Miss deer goes on to say that FDA could make more experimental drugs available faster especially for children facing life-threatening diseases talking about broadening the use of accelerated approval other tactics doctor what would you say to miss deer and other families like hers first of all we um uh are very concerned we don't want bureaucracy to hold things up um and there's always a balance as I said bet

ween giving people access to a potentially beneficial therapy and the tragedy that occurs when someone takes a therapy and it turns out to cause harm in and of itself and of course um in a place that's big with so many things going on there's always a chance that an individual situ ation will not be handled in the best possible way so I I won't comment on M Striker's particular situation but I'll just say um we're not perfect and um we as a public health agency um accept that people should be pu

blicly calling attention to areas where they think we're not doing the best job and we're going to do our best uh to try to fix it where we believe that's the case but you know Dan it's also uh true that there um there nothing as harmful as someone believing they've got a cure or treatment for a disease when they're being misled by the people that are selling that product and so we have a role to play which is set by Society to say the rule book written by Congress and we need to play by the rul

es um as does everyone the good news I think for those who want earlier access is that the American people has spoken the laws give earlier access than ever before I've just been into Europe um we had good discussions about this and I think we're doing pretty well compared to most countries but as I mentioned having said that we can always do better uh we welcome the feedback as painful as it may do and we'll try to do the best we can in the time that we have left I wanted go ahead doctor just w

anted to mention one quick thing that I want to emphasize because we've been talking about a lot lately this revolution in science is mostly about genes Gene products and the ability to intervene and affect a particular gene or a product made by a gene that's a measurable um intermediate marker so-called biomarker that's where the big action is right now and that is something where we're really thinking hard in working on how do we accelerate those Pathways because we have a pretty tried and tru

e scientific method that gives us confidence there are a whole variety of other therapies for rare disease which don't create biomarker that we can measure reliably that's a much more difficult problem that requires more of the old methods in order to have the confidence that's needed that the benefits outweigh the risk so just wanted to get that out there it's a topic that there'll be a lot of discussion about another topic where there's been quite a bit of discussion artificial intelligence yo

u've spoken about the potential of AI to improve medical research have you seen compelling evidence that that is happening well Dan I think you know my entire career has been built around practicing medicine using computers developing algorithms that are used in practice so when we say AI you know it means so many different things to different people um if you said are there examples where algorithms have been used uh to improve Target Discovery absolutely uh that is to know which targets to app

roach um if we just look at something that's really I think one of the wonders of of the world the ability to tell about the folding of genes of proteins and how that occurs that is having dramatic impact right now on uh product development the design of clinical trials has always been helped by um simulating trials in an artificial environment that's getting better and better um thanks to algorithms and AI but I think The Best Is Yet To Come and much of it will actually occurring something that

sounds mundane it's the administrative processes that are involved in research and clinical care which need to be painstaking because an error made in transferring uh something from one piece of paper to another can be critical to uh destroying a clinical trial or a drug development process or a new device um generative AI has a promise to both automate that and speed it up but also put in checking systems that are could make it much more um accurate and much easier to trace exactly who is hand

ling the data and what was done with it now that sounds very bureaucratic and administrative but um if you've ever seen where an analysis got screwed up accidentally or someone manipulated an analysis on purpose and how hard it has been to discover that uh you'd come to appreciate that um this is going to be a big area of AI it's very Akin Akin Dan to what's going to happen in clinical medicine um where that you know you probably may have been to see a doctor recently you notice the doctor is bu

sy clicking boxes on a computer to get the Belling right while also trying to talk with you generative AI is going to be able to generate those notes give us um evidence for research uh and also maybe enable your doctor and nurse to actually pay attention to you instead of the computer do you feel like there's too much hype though around AI doctor there has been talked that AI will help us cure all manner of diseases within the century are we are we overshooting its potential well all of these t

hings have life cycles of hype and despair and then back to a even point and uh AI if you look historically uh it's been through Decades of hype that then ended in despair I um I have to admit I'm an Enthusiast right now that we're going to see tremendous progress in a short period of time it's sort of a Tipping Point um if you will will it cure all of our alses no will it create new problems yes um you know hallucination of generative AI as an example where you get going and it starts making th

ings up that you didn't want to be there uh the recent problems at Google with uh drawing pictures that um were incorrect uh because of the way the algorithms were biased is another good example so it's not all uh positive regulation is going to be important because like all big-time Technologies it can do good and it could also do harm and we need to help the industry stir itself uh towards that part of doing much more good than harm but I have to admit I'm a great Enthusiast right now for the

potential just quickly to apply a rare disease imagine you have a disease that only a thousand people in the world have right now whether the right diagnosis is made is mostly a matter of where you lucky enough to see a clinician in a particular clinic at a particular Point who happen to be Thinking Beyond what most clinical people would think about in the future generative AI should give that clinician access to the world's literature instantaneously and also enable um finding out when you pres

ent with a situation that's not common that you may have a rare disease of a particular type we're seeing hints of that in what I think is a spectacular project at NIH um in the undiagnosed rare disease project being done there and then beyond that it can say let's hook you up with all the other people and have your same problem so you can find the company working on a treatment and you can get a clinical trial done I I don't think we're that far away from a situation that would look radically d

ifferent most people with rare disease now undergo what they call a diagnostic Odyssey where it takes multiple visits and often misdiagnosis through many episodes before the diagnosis is finally made I think we can change that in the 30 seconds we have left dror I'd like to take it from potential to uh present the FDA has been seeking to enact a ban on Menthol tobacco you've argued for that ban what's the status of that effort well um you know it's publicly known that um we finished our uh work

and move the the uh rule into um om and we don't control the timelines in uh om and I'm just hopeful that um this will get uh through in a short period of time we're um you know this is a high priority for us that's not news uh we've been saying it for several years now so uh all I can say is that we're hopeful okay well we are just about out of time we'll have to leave it there on Menthol and rare disease Dr calea thank you so much for joining Washington Post Live Today always a pleasure thanks

a bunch and don't go anywhere my colleague Francis Steed sellers will be back in just a minute stay with [Music] us [Music] good afternoon I'm Kate MCAS Chief corporate Affairs officer at Harmony biosciences a warm welcome to our discussion about modernizing rare disease drug and Ovation featuring our esteemed guest Congressman Greg Harper who served as the US Representative for Mississippi's thirdd Congressional District from 2009 to 2019 a dedicated Advocate and public servant for rare diseas

es he is also a devoted father to a son living with fragile ex syndrome a rare condition that's characterized by intellectual and developmental challenges before we begin our conversation I want to note that Harmony biosciences is pleased to sponsor the Washington posts inaugural program shining a light on people affected by Rare diseases in America a significance magnified as we commemorate rare disease day 2024 at Harmony we put patients at the heart of everything we do and we are committed to

elevating discussions that address both the challenges and the progress happening in rare disease research with unwavering empathy and Innovation we're excited to have Congressman Harper here today to share his insight about modernizing research for rare disease treatments with a particular emphasis on making clinical trials more accessible additionally it's worth noting that Congressman Harper consults for harmony as part of his overarching dedication to advancing Innovation and accessibility

for people living with rare diseases Congressman Harper welcome thank you so much for being with us today I want to begin our conversation by asking as both a father and an advocate for fragile syndrome would you share with us some of your insights and personal experiences of caring for someone with a rare disease okay first of all thanks for letting me be on this uh program and thank Harmony and certainly The Washington Post uh for making this available I think it's so important and when we loo

k at this it's really all about uh these these special children and they sort of are you know become our world and caregiving is is a very uh challenging aspect uh I can say that my wife did all the heavy lifting uh when Livingston our son with fragile ex was little uh she was the one that had to drive him to uh Speech Therapy occupational therapy doctor's appointments other things that needed to be done to make his life uh better but the caregiving is not just why we're trying to raise these ch

ildren with fragile X uh it's and other rare diseases it is what do we do long term what's the care giving aspect going to be when uh when they're adults uh when those parents that have poured everything into these children are gone so the caregiving issues always out there is one that we've got to continue to have that discussion um The Journey we had with uh have had with Livingston was not the journey we planned on but it's been great and we're so thankful well and you've done such a a wonder

ful job being both his father and his Advocate and really using your voice for others as well we talk a little bit about U you know all of the the responsibilities of a caregiver and when you think about participating in clinical trials can you elaborate a little bit on some of those challenges or maybe opportunities for ensuring broader participation in Trials especially for you know families like yours where there is an individual with a rare disease look it's a clinical trials are so importan

t and and so uh great uh to do but it is also keep in mind that these families have the regular challenges but then it becomes really overwhelming and these families are just they sometimes just don't know what to do maybe they don't have the resources to do these things and so you know you're dealing with all of these different therapies just the challenges of having that child with those special needs and then oh by the way do you have time to to participate in a multi-year clinical trial and

it's just it's almost too much to take in so uh the opportunities are obvious you have the opportunity to advance uh treatments uh to look for cures to to make that life better for that particular rare disease but the challenges are what do you wind up doing what can you do to make their lives a little easier to participate in that clinical trial uh perhaps it's reducing the number of actual in-person clinical visits that you need to do or you you know making sure that those parents understand t

hat there's no there's not going to be a cost to them it's going to be covered if they have to travel out of state or come spend the night or do whatever but if you can do more from home whether that's a telea health aspect or whatever it it lets those parents relax a little bit and know hey I can do this and it is for the good of my child and and I want to participate you know you you mentioned some of those flexibilities and your experience as both a congressman and an advocate uh for rare dis

ease really put you in a unique position to talk a little bit about this can you talk about you know public policies and and uh rare diseases and what things could maybe be done to to uh hasten clinical research and make trials a little more accessible well when I came into uh Congress in 2009 I was the only member of the house or Senate that had a a child with fragile X syndrome so nobody knew what fragile ex syndrome really was and so the first step for that rare disease is always increasing a

wareness uh everybody wants to go up to DC whether it's on their advocacy day or whatever it may be uh to meet with their member I will tell you that perhaps the staffer is more important than the member because the staffer is the one that has more time to spend on it uh and you want to have that that inroad there to do those things but from a policy standpoint funding is an obvious one you have to have the money to do the research on these and we we certainly want to make sure that uh the FDA h

as the the tools and resources that they need uh to go through this process and and I and I certainly think it's important from a policy standpoint that we understand that rare diseases don't have the same population uh that is there and so you have you want to have that uh flexibility uh that we would certainly believe the the FDA uh wants to get these things across the the Finish Line on clinical trials and this is something we can't do without Congress we can't do without FDA working together

on this and working together for these clinical trials to get uh to that conclusion that we believe uh can be lifechanging because every one of these families is looking for Hope and Congress uh and other agencies particularly FDA have the opportunity to give these families a a lot of hope uh that just may not exist right now oh that is so true I as we finish our our conversation here I just want to express my heartfelt thanks to Congressman Harper for sharing your invaluable insights and your

personal Journey with us today your dedication and uh and advocacy is just so amazing and I I I believe it's brought such a profound depth to our conversation here so thank you so much thank you Kate I really appreciate the opportunity and excited about the future for all of our kids thank you thank you all for joining us as well as we all work together toward a future where every patient journey is met with understanding compassion and above all as Congressman Harper said hope I'd like to now t

urn it back over to the Washington [Music] [Applause] Post [Music] [Applause] it was there where I decided I need to start a nonprofit I need to talk and meet as many scientists as [Applause] possible [Music] welcome back for those of you just joining us I'm Francis Ste S as an associate editor here at the Washington post to continue this conversation about rare disease I'm glad to welcome two more guests Katie Greg who is the co-founder of the Lily and Blair foundation and Rich Horan who is the

founder and CEO of cure rare diseases Katie and Rich a very warm welcome to Washington Post live thank you for having me we are delighted to have you both Katie I'd love to start with youim to give us a little bit of a backstory about how you came to be involved with rare disease such of course of course thank you for having me this afternoon I I continue to learn so much from commissioner caleff and Congressman Harper and of course I'm honored to be here alongside Rich so thank you again um ju

st to set the scene my daughter Lily was diagnosed with a Swift and severe neurodegenerative disease about two and a half years ago and right now she's just one of 17 known cases and when you receive a rare Ultra rare diagnosis there's these sort of personal pieces or this sort of New Normal you learn how to navigate so whether it's equipment modifications therapies medications Insurance what have you um those are sort of the immediate things I dealt with for a while and then I moved on to this

thought of well what can I do how can I have hope how can I give my daughter hope and I educated myself and I learned that 95% of rare diseases don't have an improved treatment it takes 15 years to develop a RAR disease drug 50% of rare diseases affect children and that 3,000 children die each day from a rare disease that's the size of one Super Bowl Stadium a month and I know that rare disease numbers are small but when framed that way it doesn't seem so small those numbers are not insignifican

t um those timelines are are not acceptable but they are motivating and that's sort of how I ended up as this civilian scientist right my emotional connection to the disease propelled me and in the last year we've formed our foundation participated in studies and research programs partnered with the NIH and we're at a place now where we are ready to fund some incredible programs that show promise of getting to clinical trial and I highlight these things because they're all the direct result of c

ontributions from citizen scientists myself patients patient organizations and our ability to break down silos fund raise Bridge knowledge gaps you know I am in no way a a researcher a scientist a clinici but at the end of the day Lily and Blair and too many kiddos and rare disease patients just like them don't have the luxury of time and the reality is that I am where I am today because the system is not where it should be thank you Katie for that very stirring uh introduction Rich you also hav

e a very personal connection to this field of research tell us your backstory just briefly happy to and first off you know thank you for for having me in cure rare disease uh on this this event on rare disease day uh it's it's wonderful to be here to share more uh about the story uh you know we just heard from from one story and and my story is a little bit different uh I have a younger brother who had a rare form of muscular dropy called duchan muscular distrophy and so with uh lack of availabl

e treatments or Therapeutics to help treat Terry um I formed a collaboration of researchers and clinicians across the United States to help develop a therapeutic to to help save Terry um DMD as it's abbreviated duen muscular distrophy is a fatal muscle wasting disease that's very Progressive and so like rare diseases uh time is not our friend and unfortunately given Terry's unique rare mutation uh he was sort of a rare patient within a rare disease and so over the time span of about three years

uh we went from the academic bench uh to the patient bedside with a uh genome editing therapeutic um unfortunately uh given the lateness in which we arrived to be able to treat Terry um unfortunately we we were not successful in in rescuing him from the disease uh but the basis of our our work continued with advancing Therapeutics for other rare diseases building from the framework that we'd established for Terry to help others who were in a similar boat faced with the disease that was too rare

to attract commercial interests to no fault of industry but simply because the mechanism isn't there to be able to treat ultra rare diseases as we know it today and so as we stand in 2024 we f ourselves with a situation where in a lot of these cases the technology exists to be able to tackle these diseases but the societal mechanism for how do we pay for these similar to Dr K's comments earlier um are yet to be figured out you know Katie we had commissioner Ki talk about the importance of patien

ts and their families in fighting and you use the term citizen scientist yourself tell me about some of the particular challenges for example in gaining funding to promote research what have you been through and what have you learned of course um you know rare disease drug development is incredibly expensive and it's add to that that it's extremely hard to fund raise for something that people know little to nothing about so that's where your sort of education and awareness piece comes in and thi

s is something that citizen scientists researchers um clinicians can really come together to spread that information um when you are able to get the funding then you run into additional challenges of this this bucket of funding that you do have can really be divided between finding a treatment understanding the disease if maybe you don't know the pathophysiology or the mechanism of a disease uh attracting more researchers to the field and that just kind of dilutes how much you're able to contrib

ute to any of the really equally important areas rich you referred to this extraordinary Triumph you the success you had in bringing a a treatment a custom treatment for your brother to trial as you said it didn't end the way you would hop but talk to us about some of the challenges as the leader of a nonprofit biotech of moving this process ahead because you've faced huge hurdles right oh absolutely you know I would say there's there's obviously a lot of challenges when it comes to forging A Ne

w Path where where none existed before um I I think some of the challenges that we face you know range from how do we how do we identify uh relevant investigators relevant academics working working in the space how do we bring them together um other challenges include regulatory challenges there isn't uh yet uh a framework for uh advancing ultra rare non-commercial diseases uh in a way that is uh clear and and reliable um the third Challenge and I would say one of the biggest challenges is reall

y how do we pay for for this uh you know we heard from Katie and talking about things that we have to fundraise for um conveying the message of rare disease in general is a challenge and so you know when we look at how do we sustainably pay for these Therapeutics for a population that may not be commercializable maybe there's 10 patients maybe there's 50 patients it doesn't warrant a commercial model and so you know the Big Challenge we Face nowadays is how do we convince uh payers Regulators uh

to look at ultra rare disease in a way in which it it it does make sense to provide reimbursement for a therapeutic albeit maybe not through the traditional uh manner that more common and chronic diseases have have traditionally um utilized you know casy I'm just stunned you use the number 17 um cases of the of the disease that your daughter Lily suffers from and yet you have worked to bring together experts you've worked with nahh I think to bring together experts to sort of um crowdsource the

re expertise for you tell us about that process it's taking you into NIH into these extraordinarily Arcane parts of research how's it worked what have you learned these experts we've learned we learned quite a bit um you know we are still very much a newcomer to this space but you know we've been really fortunate in our ability to sort of bring together these groups these researchers these scientists all ac across the globe the um Symposium we held in December partnering with NIH was the largest

Collective effort to date focused on denovo spg4 um we had about 30 researchers in the room when you're talking about a a nanor rare disease that is no small feet um and you know these outcomes just continue to ripple from that meeting we have calls every week we're pushing forward we're making sure that they stay connected and we're keeping that transparency there making sure those silos stay broken down and you know that's the challenge is that not one person not one group not one institution

has all of the pieces to this puzzle so that's where we as civilian scientists can kind of project manage the process if you will and try to to bridge those gaps you know we have a lot of interest from our audience and Rich I'd like to ask you a question that comes from Louise in Washington state and Louise asks what can be done to increase publicity and research support for rare diseases people shouldn't have to beg in order to stay alive just because they're unlucky wow those are powerful wor

ds from Louise they are uh and and unfortunately in a lot of cases that is the reality of the situation um sharing the family story talking about the the progress that's being made with research these things become necessary in order to convince uh individuals to to donate you know $10 $100 $1,000 whatever you have it um unfortunately that is the case right now but I I I agree with the implication of Louise's question that we need to bring more awareness to this concept that rare disease in aggr

egate is not in fact very rare uh there were some statistics earlier uh in the program that talked about the the prevalence of rare disease and and and in an effort to to build upon those statistics you know 10% of the United States is impacted by a rare disease this is more than very more talked about diseases that that we hear in the news almost every single day and so when we look at rare diseases in aggregate you know it's important that we consider how do we bring on additional funding mech

anism to treat rare disease broadly uh comments have been made from from the NIH around looking at rare diseases uh in Aggregate and I agree with those comments in the sense that we can't go Disease by disease by disease to develop treatments and Therapeutics for it'll take too long and will lose far too many people and so if we start to look at how do we employ additional policy tools more funding more streamlined and efficient funding to be able to get to the researchers who need it not with a

9-month grant review cycle but in a more efficient time scale uh that is one thing that we can do as as as a public to be able to encourage our elected officials to put pressure on organizations governmental funding bodies to encourage them to provide more funding and quicker funding for for rare disease therapeutic development um I think we we often can't look at these as commercial Endeavors many of these rare diseases will never be commercialized 17 patients or one patient is not a commercia

l Endeavor and that's okay these folks need treatment all the more uh not simply because they're one out of 17 instead of one out of 10 million so so Katie that comment of riches brings me straight to you the business of going disease to disease to disease and makes me want to ask you about your goals here are obviously you'd love to find a cure or a treatment but it feels to me as you're approaching this with broader goals too of course yeah I think um this is one of the most interest interesti

ng things to me right sort of this disease mechanism versus a path to a treatment or a cure and they're really both equally important um the pathopysiology of my daughter's disease is not completely understood we as of right now can't determine it's a gain of function a loss of function a toxic protein hlin sufficiency now that doesn't necessarily mean that we can't find a treatment or C but it does make it more challenging so it's important to know that there really is a dual importance of unde

rstanding the disease mechanism while simultaneously pursuing treatment or cure options the the pathophysi pathopysiology is valuable but waiting for a full understanding of it really can delay CL clinical research so so again 15 years to develop a drug for a rare disease is an incredibly long time and and too long for a lot of patients in the rare disease space and I think it was around 45% of Orphan drugs approved by the FDA between 1983 and 2018 uh targeted conditions with incomplete pathophy

siological understanding so that's that's a pretty persuasive number and as we make advancements in the research for a treatment or cure that can lend some valuable insights into the mechanism of the disease so you kind of get this reciprocal relationship between understanding and intervention so uh you know we definitely support uh those parallel efforts which we we were just hearing from KY about the mechanism of the disease but also we heard from commissioner Caleb about um he said he talked

about the beauty of Science and the revolution so maybe you can tell us a little bit more about what you're seeing with AI and crisper and other developments that could maybe change this landscape entirely well I I I I agree with the comments in the sense that the landscape is changing rapidly you know as I mentioned earlier a lot of the tools and Technology exist today to treat some of these most devastating diseases it's it's the it's the financing mechanisms that we lack but when we look at t

he programs that for instance cure rare disease is focused on you know we're we're looking to treat diseases uh of a neuromuscular neurodegenerative nature with techn such as genome editing can we go in for some of our diseases and actually remove toxic duplications of a genetic code that result in a in a non-functional or non-existent protein and and we are seeing that we're seeing that at the invitro level or the in the patient cell line level um as well as uh engineered and humanized animal m

odels that have a version of the humanized gene of interest in the animal uh that we're able to actually go and Incorrect and so the these tools and Technologies aren't things of sci-fi they are very much here uh instances where we're able to replace uh faulty genes delivered in a in a non-pathogenic virus for instance with uh the work that we're spearheading for limb girdle muscular distrophy uh as well as the work with antisens algon nucleotides or Asos where we are attempting to skip a toxic

part of a gene to be able to allow for the the production of a of a shorter yet functional protein as we're doing with spino cerebell taxia type 3 or Scot 3 as it's abbreviated so it's it's impressive to see that the the bread and depth of technology that exists Now by no means is it perfect uh how we deliver these Therapeutics is one of the biggest challenges especially for neuromuscular diseases muscle comprising about 40% of our body's Mass raises the challenge of how do we effectively delive

r genes that Express proteins that aren't outside the cell but are inside the cell and how how do we get inside those cells in an efficient safe and effective manner are still questions that that we continue to Grapple with but by no means is this you know the the 1940s or 50s where you know it's it's it's only small molecules or almost virtually only small molecules here we have the tools and Technology to be able to edit genes replace genes um and and fix faulty genes but we there's still a lo

t of work to do a lot of work to do and we're getting close to the end of time but ktie I would like to bring in another audience question and this one comes from Elaine in New York and elain asks might not research on rare diseases hold the key to treatments not only for those disorders but for a whole family of more common Related Disorders very interesting question yeah that's a great question I think it's so important um despite the Rarity of our our specific conditions we don't want to Disc

ount the potential for possible synergies and unexpected genetic links between seemingly distinct diseases so for example my daughter's specific mutation can be considered an upper motor neuron disease just like ALS and some of the best research in the world is focused on a cure for that and some of her symptoms present like those of someone who's had a stroke or a severe spinal injury so again there's some linkages there that can be really valuable so we need to challenge the notion of genetic

siloing even treatment of symptoms and find those common Pathways to sort of bridge those gaps between rare disease populations and larger populations Rich a last word to you but what word do you have for the largest science community and it has to be quick what message do you have about what you've learned and what they should take from these sorts of Investigations into rare diseases as they look into other disease processes well I the final word has to be collaboration right I think kako thes

e comment ments others have echoed these comments this idea that we need to put uh politics and and Publications aside and work together for the greater good um it's how we have Advanced Therapeutics it's how others have Advanced Therapeutics effectively is the idea that it's it's the patient and the patient family who are suffering the most from from this disease and that we need to put aside um differences to be able to come to work together solve these you know this is a team sport at the end

of the day drug development is is the collection of individuals who are experienced that variety of different things and that's how we've Advanced our Therapeutics effectively and efficiently at cure rare disease and that's what I would encourage others to do as well uh so that we can we can have more treatments and cures for these diseases that have historically been neglected and overlooked collaboration and working together I feel as if it's a message that Echoes Way Beyond this program so t

hank you both Katie and Rich for joining us today thank you so much for having me I really appreciate it and a special word of thanks also to Lily and Blair and Terry um thank you very much to our audience also for joining us today please do sign up for a subscription to Washington Post Live you can do so by going to wo. sdlive that's W.S sorry wo. stlive thanks so much for joining us I'm Francis Ste sers of the Washington Post