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Genomic Medicine in Pediatrics: What Pediatricians Need to Know Now · Pediatrics in Practice: A CME Podcast

• 0:01
  Dr Mike Smith (Host): Welcome to Pediatrics in Practice, a CME podcast.
• 0:05
  I'm Dr.
• 0:06
  Mike, and with me is Dr.
• 0:07
  Scott Younger from Children's Mercy.
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  He's the Director of Disease gene Engineering.
• 0:13
  Today we're diving into the fascinating world of genomic medicine and pediatrics,
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  what pediatricians need to know now, Dr.
• 0:22
  Ger, welcome to the show.
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  let's go ahead and start off with how do you define.
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  Genomic medicine and pediatrics.
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  And why is it becoming increasingly relevant for general pediatricians to
• 0:35
  know not just specialists like yourself?
• 0:38
  Dr Scott Younger: well first of all, thank you for having me on the podcast.
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  I'm excited to chat today.
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  and to get to your question, so genomic medicine is basically just the process
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  of leveraging genetic or genomic information to achieve tasks like.
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  facilitating disease diagnosis ranging all the way to guiding
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  treatment plans for patient's, right?
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  So I think about this as kind of like, maybe like a car.
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  If your car won't start, like 50 years ago, you might take it to the
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  neighborhood, mechanic and hopefully work through a process and find the problem.
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  Today, through technological advances, we have new, tools we can use.
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  We have these diagnostic boxes we can plug in.
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  and you get a code, and maybe sometimes that code says the battery cable's loose
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  And that, doesn't solve the problem, but it tells you what you need to do.
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  Sometimes that code might say, there's a problem with the fuel system.
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  Now that's more broad and there's more to, to look into, but at least
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  it gives you some direction, as to where you should be looking.
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  So that's kind of how I think about genomic medicine And the role
• 1:33
  that it plays today in pediatrics.
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  Dr Mike Smith (Host): I like that.
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  that's a good analogy but from your perspective, where is genomics already
• 1:43
  influencing pediatric care like today?
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  Like how is it being used right now?
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  Dr Scott Younger: can give you, know, two examples of things that
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  we've accomplished, in our lab.
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  one of them was, an example of a patient who we identified, the underlying
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  genetic cause of disease for specifically a Duchenne muscular dystrophy.
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  And that underlying genetic cause, was amenable to treatment
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  with type of molecule called an antisense gon nucleotide.
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  So in the lab we actually did a preclinical development of what would
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  be an individualized therapeutic that could one day be used to treat
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  just that one specific patient.
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  Again, that was all guided through the genetic diagnosis.
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  And then another case that, was really amazing, what we were able to achieve
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  in the lab, is through a genetic diagnosis, identifying the underlying
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  cause, of disease for a patient with intractable epilepsy, which ended
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  up being, faulty calcium channel.
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  We were able to search for existing drugs that targeted that calcium channel.
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  And what we were able to do was do an individualized drug repurposing.
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  So finding an available drug that we could use off-label, And that
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  was actually successfully used to resolve, seizures, the patient.
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  So again, that genetic diagnosis actually guided the treatment in
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  ways that we would not have been able to, identify without that.
• 3:00
  Dr Mike Smith (Host): Well, let's expand on that a little bit.
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  so what are some of the common clinical scenarios where a pediatrician
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  should consider, you know, whether, genomics might help provide
• 3:11
  answers for a patient or a family?
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  Dr Scott Younger: I think you have kind of two things on,
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  different ends of the spectrum.
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  One is where you, have, You know, an array of clinical presentations
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  with, very unclear etiology.
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  that's an example where you might want to dig into the genetics and
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  see if there's something there that could explain these things.
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  And then on the other end of the spectrum are scenarios where you
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  have maybe a clinical, presentation that's a little more common, but
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  really just could be caused by a wide variety of underlying issues.
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  And again, like back to that, car diagnostics analogy, just giving
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  you the information of, where should I be looking or where is the best
• 3:47
  first place to start looking, for what's causing these conditions.
• 3:51
  Dr Mike Smith (Host): You know, Dr.
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  Younger, when I was in medical school, I had a, genomic engineer once.
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  Tell me, now This is, a long time ago, right?
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  This is now in your early nineties.
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  he had said That someday I'm gonna have a book that I can just open,
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  pick the disease, pick the abnormal, gene abnormal protein, And then
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  have an answer of what to treat with And that was so impressive to me.
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  That was like, oh, that's what genes and and genomics is gonna do for us.
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  is that reasonable?
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  Is That, how someone like a, general practitioner can think about this?
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  Dr Scott Younger: That's an aspirational goal for sure.
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  That is not the way it is now or it will likely be in our lifetimes because
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  the amount of information you have to collect to truly understand these things.
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  so it's important to note because there's not a situation where
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  very few situations, I should say.
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  That, a clinical diagnosis, surge neck diagnosis, is going to give
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  you a crystal clear path forward.
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  particularly we work a lot in rare disease.
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  These diseases are complex, right?
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  So they give us tools and information.
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  but it still requires, really great, pediatricians and specialists to
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  understand the patient's and how to leverage that information to treat
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  them, as individuals in the best way.
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  Dr Mike Smith (Host): I think the genomic engineer that told us that was
• 5:02
  being a little, You know, sarcastic.
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  But
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  anyways, but, when you think about where we're at with genomic
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  medicine, and you think about.
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  some of the conditions that, you know, you've highlighted Al Al already.
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  What's your hope for this?
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  Like what do you see in the near future, far future for genomic medicine?
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  I mean, how far are we gonna be able to go?
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  Dr Scott Younger: so that's a really great question.
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  And the answer I think lies less in the technology itself and more in the
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  ways that we implement, and execute the tools, and democratize access.
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  So we've shown that we can, you know, achieve great success in certain cases.
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  but in a lot of cases, this technology is not reaching the
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  people that would need it most.
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  so the ways that we, implement genomic medicine And the healthcare system,
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  unless it is kind of boutique tools, I think that's really the path forward.
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  And the major challenge that lies ahead.
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  There's still technology, that needs to be advanced and grown and developed,
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  but, we can't set aside the fact that we've gotta figure out how to get this
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  technology to the people that need it.
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  Dr Mike Smith (Host): Yeah, it seems, and I'd like to get your
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  opinion on this, it does seem that.
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  Understanding genomic medicine a little bit more that, you know, just genetics
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  in general, that we have a greater appreciation for personalized, not just
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  personalized medicine and personalized treatment, but personalized disease
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  that a prostate cancer in me is not the same as you genetically speaking.
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  Is that true?
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  Is that something that you would agree with?
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  Dr Scott Younger: that's absolutely true.
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  and that's why, we've talked a lot about, genetic medicine or genomic medicine.
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  another area that we're advanced in, in my lab is working in what
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  we call individualized cellular models where we're able to actually.
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  take cells from a patient and develop advanced cell models in a dish, And
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  that allows us to ask questions, and do experiments, to inform us about
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  a individual's condition because, again, sequencing a genome doesn't.
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  Tell us everything And we don't fully understand the genome quite yet.
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  So even with the sequence information, there's still things we're just
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  not gonna be able to understand.
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  so each individual is unique and a disease, will present
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  uniquely in each person, And that, does need to be appreciated.
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  Dr Mike Smith (Host): maybe if, the genomic engineer that told me about that
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  book, maybe today he might say that each person's gonna have a book and you open
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  up that book for Scott Younger and if he has this issue, This is your treatment.
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  Maybe it's gonna be more like that.
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  Dr Scott Younger: Yeah, again, an aspirational goal for sure.
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  but yeah, that would be the idea that we would strive for.
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  Dr Mike Smith (Host): Now what happens, when genomic testing doesn't lead to a
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  targeted therapy or a better, therapy, how can having that diagnosis, that
• 7:48
  genetic diagnosis, change care, or support for a patient in the families?
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  Dr Scott Younger: It's important, for us to appreciate that, the going rate
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  for achieving a diagnosis from, whole genome sequencing, for example, sits
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  at around 40%, So that helps a lot of people, but it's by no means a one
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  stop shop for getting your diagnosis.
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  but what it does is it can help you rule things out.
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  it can also, potentially help you identify their communities, with,
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  similar presentations and get that kind of community, and understanding, that
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  can kind of help on the personal level.
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  even if you can't get that underlying genetic cause.
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  Dr Mike Smith (Host): You know, when it comes to genes themselves, I'm
• 8:27
  gonna back way up for a moment, and, You know, when you're talking to,
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  the patient, the parents, what have you, how do you explain all this?
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  I think most people know just with basic, even middle school.
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  Science that we all have.
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  Genes, DNA half come from mom, half come from dad, And we all, as humans,
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  we share these genes in a sense.
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  How do you explain then genetic testing And what you're actually
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  measuring and looking for?
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  Dr Scott Younger: so you each gene, encodes a protein, the
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  protein's, kind of the working unit.
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  And so what you're doing with the, genome sequencing for example,
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  we're looking across those working units that we know of.
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  We know what they do and their general processes they're involved in.
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  And that allows us to identify where, Pathways and processes aren't
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  working right inside of a cell.
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  I mentioned a calcium channel.
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  So calcium, flux plays a role in muscle contraction.
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  It can play a role in neuronal firing.
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  So that kind of tells us the underlying molecular cause and kind of
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  attribute those clinical presentations back to the underlying genetics.
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  So, it kind of just provides that, blueprint, I guess for the analogy,
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  it's the Chilton guide, I don't know if they still print those or not.
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  Dr Mike Smith (Host): I
• 9:39
  Dr Scott Younger: they they live online somewhere.
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  Yes.
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  Dr Mike Smith (Host): No, that's good.
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  I think that's helpful for pediatricians.
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  'cause you know, here's what's happening, Dr.
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  Younger, it's not just the genomic engineers like yourself with PhDs that
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  are having these conversations anymore.
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  General practitioners are having these conversations.
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  Patient's are interested in gene therapies and genetic diagnosis because they see
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  it all over social channels and stuff.
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  And so This is, I think, an important question.
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  What do pediatricians really need to understand versus what should
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  be handled by someone like you,
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  Dr Scott Younger: I was thinking about this this morning.
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  Like, I, think there is a difference between, biology, and physiology.
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  and sometimes thinking those two things always go kind of hand in hand.
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  maybe we need to take a step back.
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  So, understanding gene therapy, how it works, the implications,
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  And the underlying, technology of that, is somewhat separate than
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  the actual physiology of disease.
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  And so you do need somebody that understands the nuts and bolts, And
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  that this isn't simply, especially with genetic therapy or gene therapies,
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  these aren't your maybe typical small molecule drug that you might take or
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  prescribe a little more, or a little more available, a little more freely.
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  so I, think you do need somebody, with necessary expertise,
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  at least around to, teach.
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  Pediatrician's kind of the language that should be used and when those
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  questions should be guided to somebody with more, expertise with that knowledge.
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  Dr Mike Smith (Host): So as you study all this in research.
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  The latest developments, innovations in, genomics.
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  What do you think are the most important ones for pediatricians to be aware of?
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  and how do you see the general practitioner, the general pediatrician,
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  how do you see their role evolving in all this as your field growth?
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  Dr Scott Younger: so that comes back to an answer I gave
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  you earlier, which really is.
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  democratized access to the technology And the way that understanding or, charting
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  the path forward about how that enters into kind of more general practice.
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  I've given you examples of how we can use that information to guide treatments Now,
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  a lot of times we see in what we do is, people kind of do the proof of concept
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  where they show something can be done.
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  But really that path to getting there isn't the same path that's
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  gonna lead to widespread adoption, or implementation on a large scale.
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  So that's a different problem.
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  And so not every patient or every clinician is gonna be able to build
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  up, this giant work product to show something That is a proof of concept.
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  we need to understand where this can be implemented.
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  For example, how can we standardize or.
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  Make standard of care, to deploy genomic medicine, for example, whole
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  genome sequencing, and a pipeline that allows, the clinician to have
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  access to that information without having to do all the work themselves.
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  and I think that's really the path forward and, clinicians, pediatricians
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  are obviously gonna be required to play a role in that, because We
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  understand how the technology works, but we don't fully understand the,
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  best path forward for getting it widely
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  adopted.
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  Dr Mike Smith (Host): That's fascinating.
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  you're listening to Dr.
• 12:47
  Scott Younger from Children's Mercy.
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  He's the Director of Disease gene engineering.
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  Any last words for the listening audience about genomic medicine?
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  Dr Scott Younger: I just appreciate the opportunity to chat about this.
• 12:59
  do think we should be thinking.
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  More broadly about how we can implement the tools and technologies at scale.
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  making these more standard of care, and kind of the barriers that are
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  there, And what we need to work on.
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  Just as a broad field And in pediatrics.
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  Dr Mike Smith (Host): Dr.
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  Younger, thank you so much for coming on.
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  I have so many more questions for you, so you're gonna have to come on
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  back and talk more about this fasting.
• 13:23
  For more information, you can go to c MKC link slash CME podcast.
• 13:29
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• 13:33
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  This is Pediatrics and practice.
• 13:38
  I'm Dr.
• 13:38
  Mike.
• 13:39
  Thanks for listening.