Latest / Becker’s Healthcare -- Pediatric Leadership Podcast / Transforming Genetic Diagnostics: Dr. Paul Kruszka on the Future of Genomic Medicine

Transcript

Transforming Genetic Diagnostics: Dr. Paul Kruszka on the Future of Genomic Medicine · Becker’s Healthcare -- Pediatric Leadership Podcast

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  That's the beckershospitalreview.com
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  events page. See you in Chicago.
• 1:14
  This is Laura Dierda with the Becker's Healthcare
• 1:16
  Podcast. I'm thrilled today to be joined by
• 1:19
  doctor Paul Kruska, who's a clinical geneticist at
• 1:21
  Children's National Hospital in Washington, DC. Doctor Kruska,
• 1:24
  it's a pleasure to have you on the
• 1:25
  podcast today.
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  Yes. Thank you for having me. I really
• 1:29
  appreciate it.
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  Now I'm looking forward to our discussion. I
• 1:32
  know there's so much happening in the health
• 1:33
  care space and in particular
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  in, genomic testing, just really a fast moving
• 1:39
  field. But before we dive into the broader
• 1:41
  questions, can you tell us a little bit
• 1:43
  more about yourself and your background?
• 1:46
  Yes.
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  I'm a physician,
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  and I'm board certified in clinical genetics. This
• 1:51
  is a specialty that I find a lot
• 1:52
  of people don't know much about. We're a
• 1:54
  we're a small specialty, and
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  and what we do is we diagnose
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  and treat a large portion of rare diseases.
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  I spend most of my time as chief
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  medical officer at a company called GeneX. We
• 2:07
  do commercial testing,
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  and I'm also a
• 2:11
  faculty member at Children's National Medical Center where
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  I teach genetic residents, the next generation of
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  clinical
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  geneticists.
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  And prior to GeneDx, I spent over a
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  decade as a physician scientist researching rare diseases
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  at the National Human Genome Research
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  Institute, and that's one of the institutes
• 2:30
  National Institutes of Health in Bethesda, Maryland.
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  So, really, my my professional career centered around
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  helping families
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  and patients affected by rare disease.
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  That sounds like a fascinating role to play.
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  And given your experience, what are some of
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  the key developments in genomic testing over the
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  last 5 years or so?
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  Yes. The the the last the the last
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  5 years have been fantastic
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  for,
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  for genetic testing and and really,
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  for patients and and their families.
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  And
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  the the biggest change in the last 5
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  years has been a dramatic shift to broad
• 3:08
  based testing
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  with whole exome sequencing and whole genome
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  sequencing.
• 3:14
  For your listeners not familiar with these tests,
• 3:16
  whole genome sequencing
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  sequences our entire genetic code, if you can
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  believe it. It's all 33,000,000,000
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  base pairs of DNA,
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  our our our genetic code. And whole exome
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  sequencing
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  focuses on the exome, which consists of the
• 3:32
  protein coding regions of the genome, and this
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  is about 2% of our genome.
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  Most disease causing variation
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  in clinical genetics and genetic diseases occurs in
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  the exome.
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  But as we learn more about variation outside
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  of these protein coding regions, whole genome sequencing
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  is becoming increasingly more important. So really
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  exciting,
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  shift. And and there's there's
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  a number of reasons for this shift to
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  the broad based,
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  testing.
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  And the most important piece is that clinical
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  studies
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  clinical evidence
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  shows a higher diagnostic
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  yield for whole genome sequencing and whole exome
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  sequencing over other types of testing, such as
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  multi gene panels and chromosomal microarray.
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  Another big reason for the shift is professional
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  organizations such as the one I belong to,
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  the American College of Medical Genetics and Genomics,
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  are recommending that clinicians use whole exome sequencing
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  and whole genome sequencing as a first tier
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  test for
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  conditions such as developmental delay,
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  intellectual disability, congenital anomalies, and epilepsy.
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  And, 3rd, health insurance companies are starting to
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  pay for this.
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  Both public and private
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  payers are starting to reimburse for coxumecipacine
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  and whole genome sequencing. Matter of fact, 90%
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  of commercial payers
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  are paying for whole exome and whole genome.
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  So this is huge.
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  And then last,
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  which is is is also
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  related to to the payers, that the technology
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  is improving and the cost of these technologies
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  are dropping.
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  So exome and sequencing,
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  whole exome sequencing, and whole genome sequencing prices
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  are are dropping. So this is this testing
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  is becoming more accessible.
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  That's great to hear. You know, I'm really,
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  fascinating
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  that these tests are becoming more accessible,
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  and people's ability to really know more about
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  themselves and and prepare as well. I can
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  imagine it is really beneficial.
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  What do pediatricians
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  need to understand about the advantages of some
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  of this advanced
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  genomic testing versus other categories of genetic testing?
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  Yes.
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  They need to know a lot. So that's
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  the the the short answer. The the long
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  answer is,
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  I want I wanna group these
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  these tests into 3 buckets. So first, I've
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  already talked about broad based testing, whole exome
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  sequencing, and whole genome sequencing. So let's put
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  that in one bucket.
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  And and and both of these tests,
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  as I noted,
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  covers our entire genome. So we have 20,000
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  genes, so it covers all of that. Now
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  bucket number 2 are multi gene panels, and
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  these test 100 of genes or less.
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  And this was very popular,
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  in in the past, you know, in the
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  past 10 years because it was less expensive
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  than doing the whole genome or whole exome.
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  So second bucket, like I said, are multi
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  gene panel. And then the 3rd group is
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  something called chromosomal microarray,
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  and this was being developed back when I
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  was a a medical
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  school student and and resident in training, many
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  years ago. And this looks for large duplications
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  and deletions of our genes in our in
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  our genome, often involving millions of base pairs
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  of of DNA. So that's the 3rd bucket.
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  And so all 3 of these buckets are
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  being used today.
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  And what the pediatrician needs to know,
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  and this is the most important
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  fact that they need to know, is that
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  the diagnostic yield is significantly higher for exome
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  and genome than the other types of testing,
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  which makes sense as as exomes and genomes
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  are are much more comprehensive.
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  And rare disease discovery
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  continues to progress at a very high rate.
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  There's hundreds of new gene disease associations
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  every
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  year. So you can imagine that these panels
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  just can't get big enough to include all
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  these different genes. So broad based testing is
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  able to capture these new discoveries where a
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  panel is limited to
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  the genes that were originally placed on the
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  panel. And then there's microarray, the 3rd bucket,
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  and this looks for
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  large
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  duplications or deletions of our genome.
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  And we're talking about millions of base pairs
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  and hundreds of genes often needs deletions.
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  But, really, we want the resolution down to
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  a single base pair or single alphabet of
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  our genome, and that's where
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  whole exome sequencing and whole genome sequencing
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  really puts the bill. It gets right down
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  to single base pair changes along with what
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  microarray does anyway. So this broad based testing
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  is much more efficient, and it's better for
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  patients and their families because
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  they get a diagnosis
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  quicker. Many many clinicians today are doing what
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  we call serial testing. They'll start out with
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  a chromosomal microarray, then it move to a
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  multi gene panel. Then finally, they'll get around
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  to broad based testing with whole exome sequencing
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  or whole genome sequencing.
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  And this delays the diagnosis as I mentioned.
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  And also, it incurs unnecessary
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  medical costs. So just,
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  the medical
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  associations
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  and the payers are definitely pointing to what
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  the medical evidence says. Let's go straight to
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  broad based testing.
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  That's great to hear. You know, and really
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  powerful information for physicians and pediatricians in particular
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  is they're looking at how they can advise
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  their patients, see what really the next steps
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  are moving forward.
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  Now I'm wondering too, what are some of
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  the barriers to patient and provider access to
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  the advanced, genomic testing, and what steps need
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  to be taken in order to increase that
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  access?
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  Access to a medical provider who can order
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  and diagnose a rare condition is the biggest
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  barrier in my opinion.
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  There are very few medical geneticists in this
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  country. And as I said in the introduction,
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  I'm a medical geneticist.
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  And
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  we, the medical geneticists, are the main state
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  for ordering genetic testing in North America.
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  A recent report by the National Academies of
• 9:37
  Sciences, Engineering, and Medicine on pediatric subspecialties
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  reported that clinical geneticists
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  and of all other specialists
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  to be seen.
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  In my experience,
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  it is not unusual
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  to wait 1 year for a referral to
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  a clinical geneticist.
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  This simply is unacceptable
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  for patients to have to wait that long
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  and families. This this prolongs their suffering, but
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  also strains an already stretched health system.
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  There's also low uptake and understanding from non
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  geneticists
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  less familiar with advanced genomic testing such as
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  whole exome sequencing and whole genome sequencing.
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  As guidelines
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  and coverage continue to increase pointing to the
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  critical role of these tests in pediatric care,
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  I really want to see more non geneticists
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  like pediatricians
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  embracing these tests as a standard of care.
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  And until we get to that point, there's
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  gonna be long waiting
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  lines
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  or for patients and families to get this
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  type of testing and a precision diagnosis.
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  Another barrier is patient and family awareness about
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  genomic testing. I've spoken to many families with
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  conditions such as epilepsy or autism
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  that wish they had known about genetic testing
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  years before they received the diagnosis.
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  It's well known that less than 1 in
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  6 parents or 15%
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  of parents of undiagnosed
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  children
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  have
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  heard of or are familiar with advanced testing
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  such as whole exome sequencing or whole genome
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  sequencing.
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  So these this lack of awareness
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  testing is is really the number one barrier.
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  And I I don't I don't wanna skip
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  over commercial insurers and payers. Well, 90% of
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  commercial
• 11:27
  insurers
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  pay for this type of testing. As I
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  mentioned before,
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  in 28 states
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  cover whole genome sequencing or whole exome sequencing
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  through state Medicaid programs,
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  our payer system is still not perfect. And
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  there's certainly a lot of opportunity with payers
• 11:44
  to improve re the reimbursement process and make
• 11:48
  it easier for ordering providers to to order
• 11:50
  these tests.
• 11:53
  That's such a great point. You know that,
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  kind of closing the gap with the number
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  of providers
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  and specialists who are are doing these tests
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  plus making sure there's access from insurance and,
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  from that perspective is so crucial.
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  Looking ahead, what's on the horizon for genomic
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  medicine? What do you really see over the
• 12:11
  next few years?
• 12:13
  Yeah. That's that's something I love to talk
• 12:15
  about. I I teach medical students,
• 12:18
  here in the Washington DC area, and what
• 12:20
  I tell them is
• 12:21
  my
• 12:22
  specialty or or my career with the diagnosis,
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  and their career is gonna be in treatment.
• 12:28
  We are really in the golden age
• 12:31
  of genomic medicine right now with all these
• 12:33
  new treatments and improved testing such as whole
• 12:36
  exome and whole sequencing. So we're really in
• 12:38
  an an exciting
• 12:39
  time going forward.
• 12:42
  What I see on the horizon
• 12:44
  is eliminating the diagnostic odyssey. So there's there's
• 12:47
  a term we use a lot, and I
• 12:49
  might have mentioned it earlier
• 12:51
  in this podcast. But the diagnostic odyssey is
• 12:53
  the time when symptoms begin
• 12:56
  until a diagnosis is made.
• 12:59
  And in rare disease, it averages about 6
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  years.
• 13:03
  And I don't think any of us in
• 13:05
  the cyst in the ecosystem and the rare
• 13:07
  disease
• 13:08
  ecosystem
• 13:09
  should sleep until this time is much shorter.
• 13:11
  6 years is too long
• 13:13
  to to have a diagnosis. So as we
• 13:15
  move forward,
• 13:17
  for both children and adults,
• 13:19
  the horizon
• 13:21
  is in the future, is gonna show a
• 13:23
  decrease in the diagnostic odyssey. And there's a
• 13:26
  lot of reasons for this. One is is
• 13:28
  we've talked about in this this podcast that
• 13:31
  improved,
• 13:33
  access to whole exome and whole c whole
• 13:35
  genome sequencing.
• 13:37
  Another part that that's really gonna decrease the
• 13:41
  diagnostic odyssey
• 13:43
  is moving testing earlier in people's lives.
• 13:47
  I wanna talk just briefly about this project
• 13:49
  that's called, the Guardian Project. And there's other
• 13:52
  projects like this
• 13:54
  around the world right now. And this is
• 13:57
  where we
• 13:58
  expand newborn screening to diagnose
• 14:01
  more rare diseases
• 14:03
  earlier and presumably healthy
• 14:05
  infants before
• 14:07
  symptoms set in and and and cause harm
• 14:09
  to to these infants. And there's a there's
• 14:11
  really an exciting project
• 14:13
  that is taking place in New York City
• 14:15
  through Columbia University,
• 14:17
  the New York State Health Department,
• 14:20
  and,
• 14:21
  GNDX, the the company where I spend a
• 14:24
  lot of time. And we're newborn
• 14:26
  screening newborn screening traditional newborn screening that's supplemented
• 14:30
  with whole genome sequencing technology.
• 14:33
  And this program has sequenced over 10,000
• 14:37
  babies in New York City.
• 14:39
  And a test for an additional 450
• 14:42
  rare disease conditions
• 14:44
  that are actionable.
• 14:45
  And so you can imagine instead of diagnosing
• 14:48
  a child who has suffered 10 years without
• 14:50
  knowing to diagnosis, you're diagnosing
• 14:53
  these conditions in infancy.
• 14:55
  And like I said, over 10,000 infants have
• 14:57
  been completed. We're seeing a diagnostic yield about
• 15:00
  3%. So 3% of individuals are getting the
• 15:03
  test, and the consent rate is surprisingly high.
• 15:06
  This is a research project,
• 15:08
  through Columbia University in in New York City,
• 15:11
  and the the consent rate is over 70%.
• 15:14
  So this is really fantastic. This is an
• 15:16
  example
• 15:18
  of diagnosing
• 15:20
  rare disease
• 15:22
  earlier in in in cutting out that diagnostic
• 15:24
  odyssey. And then there's a lot of other
• 15:26
  really exciting things that that are happening in
• 15:29
  in North America.
• 15:31
  A lot of neonatal intensive care units or
• 15:34
  NICUs are starting to do what we call
• 15:36
  rapid whole genome sequencing in the NICUs where
• 15:39
  we have critically ill infants,
• 15:41
  and they're doing testing.
• 15:43
  And it gives these these infants
• 15:46
  a diagnosis and allows for a precision therapy.
• 15:49
  So
• 15:50
  moving the needle earlier and earlier,
• 15:53
  is gonna be extremely helpful. And I and
• 15:56
  as we move forward in the next 5
• 15:58
  years, you're gonna see a lot of these
• 16:01
  earlier testing,
• 16:03
  programs implemented.
• 16:06
  So this is this these are some of
• 16:08
  the the things that I see on the
• 16:10
  horizon.
• 16:11
  And and then the last thing is is
• 16:13
  what we talked about before, I think.
• 16:16
  Pediatricians
• 16:17
  and non geneticists are gonna take the the
• 16:19
  baton from geneticists and and really
• 16:23
  decrease those long waiting
• 16:25
  lines
• 16:26
  for for,
• 16:27
  care and testing.
• 16:30
  That's fascinating. Doctor Kruska, thank you so much
• 16:32
  for joining us on the podcast today. This
• 16:34
  is a really informative and interesting discussion, and
• 16:37
  I look forward to connecting with you again
• 16:38
  soon.
• 16:40
  Yes. Thank you for having me, and and
• 16:42
  I I really enjoyed speaking and and and
• 16:45
  really wanna get the word out about the
• 16:47
  diagnostic odyssey is alive and well at 6
• 16:50
  years, and and we really we really need
• 16:52
  to to make that smaller.