Julia Vitarello, Rich Scott and Ana Lisa Tavares: Treating Mila - Lessons for those living with rare conditions

29 February marks Rare Disease Day. This day is an opportunity
for the rare community to come together to raise awareness of the
common issues affecting those living with rare conditions. A rare
condition is a condition that affects less than one in 2,000 in
the population, and although rare conditions are individually
rare they are collectively common. It is estimated that there are
over 7,000 rare conditions. Around 80% of rare conditions have an
identified genetic origin.


In this episode of the G Word, our host Julia Vitarello, Founder
and CEO of Mila’s Miracle Foundation, is joined by Rich Scott,
Interim CEO for Genomics England, and Ana Lisa Tavares, Clinical
Lead for Rare Disease Research at Genomics England, as they
discuss challenges for those living with a rare condition and the
work being carried out across the genomics ecosystem to support
them.


Julia is the mother of Mila, a young girl who was diagnosed with
a rare genetic condition called Batten Disease, and in this
episode Julia takes us through Mila's story, and how she hopes to
help many more families access treatments for their children.


 


"So when parents, children, are diagnosed whether it’s a fatal or
life-longing debilitating or difficult disease, if you know that
what’s being learned from your child both from just the genomics
to the potential treatments that’s helping the next child, that
helps parents like me be able to continue living."


 


You can find out more about Mila's story in our previous podcast
episode with Rich Scott, Julia Vitarello and Dr Tim Yu.


 


You can download the transcript or read it below.


Julia: Welcome to the G Word


So my life at that point seemed to just disappear in that moment,
all the things that had mattered to me were gone; I knew there
was something wrong with my daughter but I had absolutely no idea
that a typical child who was outgoing and active and verbal and
had friends could suddenly lose all of her abilities and die.


My name is Julia Vitarello, and I’m your host for today’s
episode. Today joining me in conversation is Rich Scott, Interim
CEO for Genomics England, and Ana Lisa Tavares, Clinical Lead for
Rare Disease Research, also at Genomics England. Today we’ll be
discussing challenges for those living with a rare condition and
the work being carried out across the genomics ecosystem to
support them. If you enjoy today’s episode, please like, share
and rate the G Word on wherever you listen to your podcasts.


The 29th of February marks rare disease day. This day is an
opportunity for the rare community to come together to raise
awareness of the common issues affecting those living with rare
conditions. A rare condition is a condition that affects less
than one in 2,000 in the population, and although rare conditions
are individually rare they are collectively common. It is
estimated that there are over 7,000 rare conditions. Around 80%
of rare conditions have an identified genetic origin.


Before I get into speaking with Rich and Ana Lisa, I wanted to
share my story and my daughter, Mila’s, story. My life as a
mother started really like anyone else’s, my daughter was
perfectly healthy, her name is Mila. For the first three or four
years of her life she was like any other kid. I live in Colorado
in the United States, my daughter was a skier, she was a hiker,
she was rock climbing, she was incredibly active and singing
songs and swimming and riding bikes. But around four years’ old
she started tripping and falling, she started pulling books and
toys up closely to her face; she started being covered in
bruises, getting stuck on words and repeating her sentences and I
brought her to about 100 different doctors and therapists around
the United States to try to figure out what was going on with
her.


Around four years’ old I started speaking with orthopaedic
surgeons, with ophthalmologists, with neurologists, with speech
therapists and each one of them, you know, told me pretty much
that I was a crazy mom and that my daughter was typical and
normal and that she would grow out of these sort of strange
symptoms that she was having.     


By the time that she was six years’ old, I had had enough and I
was crying on a regular basis, no doctor could help me and I was
tired of lugging my daughter, who was now covered in bruises and
tripping and falling and stuttering, together with my newborn son
at the time, kind of around the country only to be told that I
was crazy. And at that point at six years’ old I brought her into
the emergency room in the Children’s Hospital Colorado, near
where I live. She was in there for about a week and underwent a
battery of tests and at the end of that week I was told that my
daughter had a rare genetic condition called Batten Disease and
that she would lose all of her abilities and die in the next few
years. So my life at that point, first four years of my life
seemed to just disappear in that moment, all the things that had
mattered to me were gone. I knew there was something wrong with
my daughter but I had absolutely no idea that a typical child who
was outgoing and active and verbal and had friends could suddenly
lose all of her abilities and die.


After crying on my closet floor pretty much most of the day for a
few weeks I picked myself up. I started to read white papers, I
started to go online and learn about other rare conditions. I
started to speak with parents that had fought for their children
with physicians, with researchers, and did everything I could to
kind of figure out if there was even a glimmer of hope. And what
I was told at the time at the end of 2016 was that there is
almost nothing that could be done and very little was known about
my daughter’s form of Batten Disease. But that there was a tiny
glimmer of hope that we could maybe stop genetic disease, and
that’s all I needed. I started Mila’s Miracle Foundation, which
is a non-profit organization. I started telling Mila’s story and
taking care of my kids by day and trying to fight and learn and
raise money by night and I started a gene replacement therapy
because it was the only option that I could take on as we didn’t
know much at all about the disease, and by replacing it, it was
kind of the only thing that I could do, but it was going to take
many years and millions and millions of dollars and I knew that
it wouldn’t be in time for my daughter.


Along the way, there was something a little bit unusual which was
that my daughter had an auto recessive disease which meant that
she needed to have a mutation in the same Batten causing gene
from her mom, myself, and her father, and they could only find
one of these two. That led me to learn about whole genome
sequencing, which was kind of the most extensive way of looking
at Mila’s genome to figure out where this missing mutation was.
And in that search I crossed paths with a Dr Timothy Yu at Boston
Children’s Hospital, and he volunteered with his lab to help me
find this missing mutation that no other lab could possibly find.
And within a few months and a lot of work, a lot of late nights
and weekends and staring at screens, through whole genome
sequencing, the team was able to find Mila’s missing mutation and
finally diagnose her fully with this rare form of an already rare
Batten disease.


That is where Mila’s story changed and turned direction. At that
point, a recently approved drug for spinal muscular atrophy was
on all neurologists’ minds at that moment because it had just
been approved in the US by the FDA and in other countries, and it
was a game changer, these children were dying and on respirators
and in wheelchairs you know at the age of two and with this new
drug they were actually living, many of them were living long
lives and were active and happy and healthy and going to school.
And Mila looking her whole genome sequence was able to kind of
fit that same criteria, and so the doctors, including Dr Yu said,
“What if we did the same thing for these children? What if we
made a drug like this for Mila?” This drug called Antisense
Oligonucleotides, or ASO seemed to be a good fit for Mila’s
mutation. And so a drug was made for Mila and named after her
called Milasen and it was a race against time for an entire a
year with a team of honestly hundreds of people across academics
and industry, I was fighting to try to raise the money and
awareness and working with a scientific team. And one year after
Mila was diagnosed when she turned seven years’ old, we moved to
Boston and Mila began receiving Milasen, which was named after
her, and only in that moment in time did I realise not only what
a big deal this was for me as her mother, but what a big deal
this was for science.


She was the first person in the world to receive a medicine that
was tailored just to one person and it was named after her
because there was no-one else in the world they could find that
shared that same mutation.


When Mila began this, you know, I didn’t know what to expect but
I knew that she was going to lose all her abilities and die if
she didn’t receive this. And so once she started receiving this
within just a few months, her 30 seizures a day went down to
nothing; she had occasional small tiny seizures that were barely
visible but her quality of life was incredibly you know improved,
not to mention our family’s because she was no longer thrashing
and smashing her arms and legs up against walls and tables.


She had been slumped and could no longer sit up. She could no
longer hold her body up and take steps with my support from
behind and after Milasen she started being able to do that even
walk up the stairs with alternating feet with me supporting her
from behind. She also had received a G-tube and was receiving all
of her nutrition through the G-tube and after Milasen she started
eating by mouth, it wasn’t perfect, but she was eating pureed
foods, and being able to swallow better and probably most
importantly she was able to smile and laugh at the funny parts in
the books and the stories that I had been reading and singing to
her and that she had kind of really not been responding to as
much before Milasen and some of that came back.


So, a year into this everyone was quite shocked that Mila had
done so incredibly well in this first year despite how progressed
she was, progressed her condition was. Unfortunately in the
second year it was during COVID and it was unclear whether or not
Mila’s disease had kind of stopped or whether it was slowly
progressing and in the third year Mila started having problems
associated with her rare condition and I was faced as a mother
with the most horrible decisions anyone should ever, never,
never, never have to face to decide what Mila would want if she
were able to talk and tell me whether or not this was a life that
she felt like she would want to live. And after three years on
Milasen, which was three years ago almost this week, Mila died
and in many ways my life as I knew it was kind of over. I’m a
very positive happy person and I have a son and I continue
getting up every day and pushing through the day but I’m not sure
how any parent makes it through days, weeks, months and their
whole life without their child physically there with them.


Ana Lisa: We can really hear the perseverance that you had to get
a diagnosis through whole genome sequencing eventually for Mila.
Can you tell us a little bit more about that process and what
that diagnosis, what did it mean for Mila and for your family?


Julia: When Mila was first diagnosed with Batten Disease, one of
the missing mutations could not be found by any lab. I did
research and found out that whole genome sequencing which at the
time was very, very hard to find a lab that would do it or anyone
that would do it in the United States, I did learn that that was
really what was needed in order to try to really get down to find
the underlying genetic cause of Mila’s disease and give her a
full diagnosis. So once we managed to have Dr Yu’s lab at Boston
Children's Hospital carry out the whole genome sequence,
obviously we were able to then find exactly where the broken,
underlying broken kind of genetic mutation was and why that was
important was for two reasons: 1) was so that we could actually
have a diagnosis and even though it was the worst diagnosis we
could have ever asked for, at least there was an answer and for
so many years I didn’t have an answer and there is nothing worse
than seeing your child, you know, having all of these different
symptoms and problems and having you know tens, if not hundreds,
of different doctors and therapists tell you that they don’t know
and maybe you’re just a little bit over-worked and over-worried
about things, and having no answer and no idea what’s wrong is
like living in this limbo that’s just terrible.


And so whole genome sequencing allowed for us to have a full
diagnosis for Mila, and it also allowed us to use that data since
it was truly the precise place where, you know, we could find the
precise plan where her gene was broken. It allowed the
researchers to then also think about what could be done about it
as well, which is the second thing a parent thinks about after
they have the kind of relief in some ways, which is a strange
word to use but it’s true, of knowing what is wrong and then
thinking, “What could I do about it now?” And so for me I would
say that’s how, Ana Lisa, that’s how I reacted to that, is there
was enormous relief initially, which is just the weirdest word
ever to use for that but at least I felt like I wasn’t crazy and
that there was an actual reason and that it allowed us, allowed
me and others to think what kind of action can we take now.


Rich: One of the things that often strikes me, I’m a clinical
geneticist by background, just like Ana Lisa, is how often
particularly several years ago when we were in a different
situation, it depended on families and parents pushing and
pushing and pushing and asking, that’s something I think in the
UK we’re really lucky that there have been changes in terms of
availability of testing. Julia, as you know, we were set up ten
years ago initially to run a project, a research project in
partnership with the NHS called ‘The 100,000 Genome Project’
asking the question about whether whole genome sequencing could
be used in a diagnostic setting. Whole genome sequencing had just
emerged as a thing that could even be conceived of as affordable
in a healthcare system back then, and we worked with the NHS and
tens of thousands of families with rare conditions and people
with cancer to ask that question and again, we’re really proud of
what that work and our partnership with the NHS has led to, which
is now in the UK.


There is the availability nationally of whole genome sequencing
to test in certain settings including in rare conditions that are
hard to solve in this sort of way and it’s one of the things
which has really changed the way we can go about this, but we
also know that there’s still, it’s still hard often to identify
who should be seen by a specialist who might do a test and so on.
But it has really changed things and I think it’s hearing from
families like yours about how challenging it is and thinking
about how we turn, looking across all of the story that you told
us of everything you went through, how we can make that be
something where we can make it be more systematically available
and work for many more people, and I know your phrase from Mila
to millions really strikes a chord with me, and I know with the
NHS mind-set here in the UK where it’s about equity of access and
I think that mind-set that you bring is so important.


Julia: Yes, Rich, I think it’s a really good point you know,
because a lot of parents like myself, we’re talking about
probably millions around the world and tens of thousands just in
the UK alone, spend so much time going from one physician to
another and to a therapist and it takes an enormous amount of
energy and time in a family that’s already dealing with pain and
confusion and not understanding what’s going on, not to mention
usually that child, in my case, Mila, is having problems that
it’s not easy to leave the house and get in the car and go to all
these appointments. And the more we can push towards whole genome
sequencing as one of the first places to go, if not the first
place to go, the more it’s going to cut that sort of diagnostic
odyssey down to the very bare minimal.


And so of course a dream would be is that any child that has, I
like to think of it as soon as you kind of have more than one
symptom that shouldn’t normally go together, that sort of has a
little red flag that goes off and in most parts of the world
right now no physician wants to scare a parent like me, it’s
happened a number of times to me where a physician has said,
“Well, you know, there is this rare condition but I’m not going
to bring that up because it’s so rare that the likelihood that
your daughter has that, I wouldn’t want to scare you.” But the
more we can move towards whole genome sequencing right away to
help with that answer that could cut months and very often years
from that odyssey, and that is where we need to be, we can’t have
the tapping on the knee and stacking up blocks and running down
the hall for months and years just to figure out what’s going on.


Ana Lisa: And I think Rich also there said a power of having a
national healthcare service where patients who are having whole
genome sequencing can also decide whether they wish to consent to
be part of research and combining that with a national genomic
research library and then the ability to work so closely with the
NHS and go back to patients if there is a new diagnosis that
could benefit them is really powerful I think, and that’s
definitely one thing that we’ve also learnt from these big whole
genome sequencing efforts is that our knowledge is continuing to
develop and some people will get a diagnosis from that
immediately and we’ve got amazing colleagues working on
diagnostic discovery looking at whole cohorts of patients now who
are having whole genome sequencing and that’s also been really
informative and allowed a lot of new diagnoses identified also
through research and through these efforts to be found.


Julia: Absolutely and I think that the UK is incredibly well
suited to have such widespread sort of country-wide whole genome
sequencing project like what Genomics England has done because
you have one system where all of the clinical and genetic data
can all come in and kind of be analysed both for like you said
diagnostics but also it could be, if families and patients are
interested, right, in contributing to the research which then
comes full circle and helps the entire system benefit from better
treatments you know and better understanding of diseases.


Rich: And that point of sort of thinking about how to move things
forward, so the NHS has a service based in Exeter which is
addressing the question where children are on intensive care,
where often intervention is needed really rapidly to make a
difference, so that’s one of the examples where sort of thinking
about making sure that service is available early and rapidly is
being set up and that’s been really successful and identifying a
cause where that really changes the care of that child on
intensive care.


The other area where we’re working really closely with the NHS at
the moment, as you know, Julia, and in fact I think this was
probably one of the reasons we first came to talk to you was
thinking about our newborn genomes programme where if you like,
the big question there is saying we know that there are a few
hundred conditions that are within that longer list of rare
conditions where there is a treatment available routinely if the
diagnosis is made, and saying could we use whole genome
sequencing alongside existing newborn heel prick testing which in
the UK currently looks for nine, shortly to be ten, conditions.
So we’re just about to launch that programme and that will
sequence the genomes of 100,000 babies born at maternity
hospitals, not selected for children where there’s something, a
concern, raised, but any baby at that hospital would be eligible
for the family to choose to join that research programme and
really to ask that question about whether this is something that
we should offer to all babies developing the scientific evidence
around it, learning about how you might implement it in practice,
and also having conversations about how one might do that, what
public attitudes are to it and so forth, developing evidence that
can move us forward in that area too.


And back to Ana Lisa’s point about improving knowledge, we know
that today there are a certain number of conditions that one
might think are comparable to those nine that are currently
looked for in the UK on the heel prick that we could use genetics
as a way in. We also know that through the sort of innovation and
the new knowledge that you mentioned that was relevant to Mila,
that list might grow quite considerably in the coming years, so
it’s thinking about how we set ourselves up to make sure that
we’re able to take advantage of that to its full.


Julia: Yeah, and I think it’s a great, I’m glad you brought this
up Rich because the UK really is leading the world in this, there
is no-one else that is doing whole genome sequencing at birth,
and ultimately, that’s where we need to be. You know it’s not
going to happen overnight and like you said, the purpose of this
is really to learn a lot about how and if to roll this out maybe
in a larger scale way across the UK. But ultimately, you know, as
Mila’s mom, I think all the time about you know how incredible
what I saw at a very progressed state for Mila with this
treatment and the only way to actually really truly help Mila and
other Milas is to get to these children early enough so that
they’re diagnosed before they have symptoms and they’re treated
before they have symptoms. And the way to move towards that is to
at least have efforts like the project, you know, the newborn
screening project so that we can get to children, find them
before they have symptoms, treat them before that and from what I
saw from Mila I feel pretty strongly that if Mila had received
Milasen at birth she might never know the effects of Batten
Disease, and we as a family might never know what it’s like
living with a rare condition, and this is a step in that
direction to help.


Effie Parks: Hi there, I’m Effie Parks, mom to Ford, who lives
with a rare neurodevelopmental disorder called CTNNB1 and the
host of the Once Upon a Gene podcast. Our show connects families
facing rare diseases, offering stories from parents, insights
from experts and discussions on everything from navigating grief
to exploring genetic advances. It’s a space for understanding,
connection and empowerment. For support and inspiration on your
rare disease journey, subscribe to the Once Upon a Gene podcast
on your favourite podcast app and let’s navigate this path
together.


Ana Lisa: Julia, I’m interested to hear what you think the
development of individualised medicines like the N1 treatment
Mila had what that means for the sort of collaboration that’s
required across the genomics ecosystem to achieve that.


Julia: Yeah, that’s a really good question. It’s been seven years
that I’ve been thinking about this kind of individualised
medicine concept, you know, as Mila kind of became the pioneer in
this field and I’m not a scientist, I’m not a physician, but I’ve
learned a lot because I’ve been fortunate enough to be part of
thousands and thousands of conversations, including with all of
you and others, Genomics England, and around the world and I
think what I learned and what I’ve learned so far is that when
you have a genetic condition most genetic conditions are
individually rare and unfortunately that doesn’t make them very
suited to have anyone go after a treatment for them because
really the only way to connect a patient, a child like Mila, to a
science or technology is if they’re lucky enough, and I hate to
use the word ‘lucky’ but they’re lucky enough to be part of a
large kind of cohort of people, and that allows them to be, you
know, commercially viable, so a company will be maybe develop if
they’re lucky, a treatment for that, for those people.


The only other option is this sort of like Herculean effort of
which myself and Dr Yu and others went through, we had to raise
millions of dollars and get hundreds of people to get on board
and develop a novel medicine for one person – now how scalable is
that? How many times can we do that, right? And so the only
people that really have access to medicines today with genetic
conditions are those that are fortunate to be part of one of
these two groups, but what about everyone else which is 95% of
the people?


And so I think what the field is learning is that we kind of have
the patients and we’re finding them, especially thanks to
Genomics England and others, we’re starting to find them more
rapidly earlier, more of them, and we have these technologies to
be able to not only find them but to also treat them but we just
do not have the infrastructure and the processes to connect them,
we have clinical trials and we have these sort of named patient
route but we don’t have anything else. And so I think the
genomics community, especially in the UK because it’s so well
suited with all the efforts that we’ve just brought up, is really
well suited to kind of try to work together to allow for access
kind of no matter how many people could benefit, it’s not only
one, it could be six or 20, or 200 or 500. Right now there is no
access for them. So I think that the UK is really well suited,
starting with whole genome sequencing, that’s where it begins, it
begins by identifying patients early enough and getting the data
that’s needed in order to diagnose them and also to help with the
treatment you know, and so this is how I think the UK is really
leading the world right now, including in the recent announcement
of the rare therapies launch pad, which Genomics England is part
of, I am part of, others are part of, Oxford Harrington Rare
Disease Centre, the MHRA, others are all part of really trying to
be dedicated to building the infrastructure and resources and
processes that are needed to connect the patients to these
technologies that exist today.


Rich: I’ve been really inspired by the conversations and the
drive that you, Julia, personally have given to those
conversations. And I think what’s really interesting and I think
it’s relevant more broadly than just in rare therapies
particularly, but I think that challenge of recognising the need
for the system to change to be able to respond to evidence and
make the response proportionate to the expectations of various
people, the patients or the families who are receiving it, the
system as a whole, these sorts of therapies and rare conditions
as well, are just not the shape that works well with existing
paradigms, but I think it’s relevant you know, in other settings
as well.


I’m really interested in some of the conversations that I’ve had
with you before about balancing risk and understanding how to get
that right and the fact that that really needs an open discussion
in public to also understand the journey and the situation that
families find themselves in. I wonder if you could tell us a bit
about your perspective on getting that risk balance right?


Julia: Thanks for bringing that up, Rich. I think it’s really,
really important because to me the way we think of risk and
benefit and the risk tolerance maybe is a better way to put it is
the foundation of the house that we’re building. So, you know,
the regulatory process and everything behind that are built on
top of how we think about risk. And one of the things that I
regularly think about is children that have end stage cancer, and
that we as a society have accepted an enormous amount of risk for
a child at end-stage cancer that has no other options that’s
going to die no matter what, probably very rapidly and that if
they don’t respond to kind of some of the main line treatments
then to turn to an experimental cancer treatment which carries a
very high risk is considered very acceptable by our society and
that everyone, the clinicians, the families, the regulators,
everyone is willing to take that risk for that child because
they’re going to die otherwise. And they’re willing to spend
money and they’re willing to take the risk and often perhaps to
buy that child maybe three or six months of life.


So then if you look at Mila and if I tell you that instead of
having a rare condition that she has an end-stage genetic
disease, and I use the words from cancer, from oncology, is now
suddenly the discussion changes a little bit, so Mila’s going to
die no matter what, no child has ever lived with her form of
Batten Disease and she’s going to lose all of her ability, so we
know the risk of not treating Mila. The risk of treating Mila in
this case was an antisense oligonucleotide, which is a modality
that’s been around for 30+ years, tested in animals and more
frequently in numerous humans across different sort of trials.
And the labs that worked on Mila’s medicine felt that it was safe
enough and hopefully efficacious enough. And at that point why is
the hurdle so exponentially higher than what it would be for a
child with end-stage cancer? The way that we are thinking about
these children with end-stage genetic disease and end-stage
cancer, is drastically different, so we need to first, to your
point Rich, we need to start realising we’ve already set that
precedent, we don’t need to be having this discussion again. We
know the risk we’re willing to take for a dying child when
there’s no other therapeutic, no other option and they’re going
to die no matter what. So the risk of treating Mila, versus the
risk of not treating Mila is black and white and we need to do
our best and then we need to not only treat Mila but we need to
learn from the treatment of Mila. We need to collect those
learnings, they must be iterative learnings so that the next
child that’s treated with an individualised different ASO or
different medicine that they don’t happen in silos, but that all
of this knowledge comes together so that the second and the third
and the fourth and the tenth and the twentieth, the process gets
better and faster and eventually cheaper so that it’s accessible.


Rich: Yes, and that’s very much back to Ana Lisa’s point on the
link and for diagnostics too on continuing to learn and creating
a system that recognises that that’s crucial to offering the best
care today but also in the future and being able to make
proactive decisions more confidently if you’re a policymaker,
knowing that you’ll continue to learn, you don’t have to pretend
you know everything today.


Julia: It’s very meaningful for parents. So when parents,
children, are diagnosed whether it’s a fatal or life-longing
debilitating or difficult disease, if you know that what’s being
learned from your child both from just the genomics to the
potential treatments that that’s helping the next child, that
helps parents like me be able to continue living. And so you
know, research is this kind of generic word, I wish there were a
better word for it. Really what it is, is it’s learnings and it’s
what can be learned from my child that can help the next child?


Ana Lisa: And then that learning requires a lot of collaboration,
which is the super important part I think of your story.


Julia: Yes, it does, it requires a lot of people starting with
those diagnosing the children with whole genome sequencing all
the way through just to the clinicians who are in the NHS, not to
mention the researchers who are then looking at the data and
bettering their understanding.


Ana Lisa: I think there are also, maybe one can extend some of
those parallels as well, in that I think currently we sometimes
think of an individualised therapy of NF1 as being something that
takes a lot of time and benefits an individual, and actually if
we can really collaborate we can really set up processes that
work across the ecosystem and keep learning, then I’d love to
dream that actually this could help many, many different
patients, with many, many different types of rare conditions
because actually we’ve learnt how to target a little bit more at
source, perhaps a particular type of genetic variant, and so a
bit like cancer, we’re not thinking about breast cancer, we’re
thinking about what sub-type, what genetic causes there are and
targeting those, and if we can apply that one day more broadly
across rare conditions then it might be that actually once you’ve
learnt a certain amount, that you could scale up and treat many,
many different conditions, not dependent on their frequency in
the population.


Julia: Yeah, that’s a great dream, I share that dream. Rich, what
is your, you’ve been in this for many years, what’s your dream
for the next five, ten years?


Rich: I guess I have, I think there’s two aspects to it. I think
there’s two, I think there’s a lot of distance left to run for us
improving on the diagnostics and I think thinking back to your
conceptualisation of it Julia, of sort of thinking about how we
can bring that earlier, whether that is that for example we’re
able to sort of more proactively flag when children have you
know, more than one visit to a particular type of doctor or
something that makes that happen much earlier in the process. So
the tooling that we now know works whether it’s whole genome
sequencing or something more targeted can be used earlier in the
process, or whether for example in our newborn genomes programme
we get that evidence that we can look for a broader range of
conditions in a screening context right at the beginning of life.


And I think in five to ten years we should be in a substantially
different place, we’ll know whether or not we think whole genome
sequencing should be there but offered for every baby at birth,
and we can be much more proactive also when symptoms arise. I
would also hope that on the side of therapies and intervention,
we’re in a substantially different position and I think, I’ve
been amazed the last five years how my level of hope has
increased. I believe we should now be in a position in five to
ten years where those with a therapy that is potentially there to
benefit them, should at least be able to be aware of it and there
will be a clear pathway by which either that is available if it’s
proven, or there’s a pathway that we all understand about how
that can be trialled. And I think we’re at the beginning of that
journey and I now feel it’s a responsibility of ours to work
through how we can bring the right pieces into place, we can’t
prejudge the science, but we can set up the system that makes us
be able to respond to it.


Julia: Yeah, I remember Rich when you and I were speaking a
number of months ago and maybe you could share the story because
you talked about your hope kind of changing over time as a
clinician I thought that was really powerful to me.


Rich: Yeah, I remember it’s probably now maybe 15 years ago being
asked by a family about what my advice would be to them on the
likelihood of there being a treatment for their child’s
particular condition being available and in fact they asked me to
do it in a way that I sort of provided a formal written report to
them that I spent a lot of time thinking about and agonising over
and was very honestly you know saying it was highly unlikely that
something would become available. If I had to write that same
report today it would be very different.


Julia: That’s so promising to hear that. I don’t know, Ana Lisa,
have you had any experiences like that in the past that you feel
differently now of how you would approach a family like mine?


Ana Lisa: I think it’s a real balance between having that hope
ourselves, sharing that hope with other people and not giving
false hope and it’s such a balance when right now more than 95%
of rare diseases don’t have a treatment and I think that’s such a
difficult position to be in right now. And everything we’ve been
talking about gives me massive hope for the future and a lot of
what we’re pouring our energy and efforts into is both the
diagnostics so that we’re not trying to make a puzzle with
missing pieces in the dark and that’s mission-critical, and then
the real hope that actually this will drive therapies, which is
what we really want for everybody who needs a therapy to have a
therapy that’s effective, whether they’ve got a common condition,
a rare condition and that’s our driving ideal.


So I think I’m full of hope and optimism and I hope that it will
accelerate, that’s what I really hope, the momentum will build
and we’ll get to a certain level of knowledge, we’re learning the
processes, we’re learning the evidence, we’re learning the
collaborative models that are needed to really suddenly explode
our ability to treat rare conditions.


Julia: Yeah, you know when Mila was, I guess when I look at
newborn screening in the United States and Batten CLN7, which is
Mila’s kind of sub-type of her condition is not on newborn
screening tests because there is no treatment for it, but the
whole genome sequencing that was done for Mila was the data that
we got from that was what was needed to create a treatment for
her and so it’s an unusual case where she was sequenced and a
child and a baby, a newborn in the UK could be sequenced and not
only told that they have a disease, so they have time to kind of
understand the disease more but also potentially kind of prepare
for a treatment that might be in the pipeline, but that data is
also going to help scientists and researchers create new
treatments that may not be available when that child is born but
that’s the data that’s needed to create the treatment.


Right now you guys are you’re really at the forefront of solving
both halves of the what I consider like a rare condition, you
know, global health crisis with tens and hundreds of millions of
people that have you know families like mine, like my story
sounds unique, it sounds impossible but there are tens of
millions of other people like me, like my story sounds unique, it
sounds impossible but there is tens of millions of other people
like me and so to have the UK kind of leading this effort to
solve both halves of the problem, the diagnostic half, you know,
what disease does a child have and find it in time and also kind
of the treatments, here’s where we’re headed, and if we don’t
solve both of those problems then there is no such as access, you
know to a better life, so I’m really grateful for the fact that
you’ve set a precedent for other countries because now finally
there are other countries that are looking towards you and kind
of really trying to do the same thing that you’re doing.


Rich: Yeah, well I think we feel we’re uniquely placed; the NHS
in the UK and for Genomics England our partnership with the NHS,
together with a number of other factors and I think the
recognition from government as well as the NHS over a long period
that the importance and the power of genomics and the importance
of for example, making changes to regulation to get it right mean
that it’s something that I think we feel really privileged to be
in the position to even be able to ask these big questions.


Julia: yeah, I think the UK is really uniquely suited to have
hung their hat on genomics so that the topics you’re taking on
are very central, they’re not kind of on the sideline, they seem
whenever I’m in the UK they say that what Genomics England is
doing is at the forefront and in the middle of all the
discussions with academics and companies and regulators and
government. What do both of you think are the, what are the
biggest kind of hurdles we have coming a few years in the newborn
programme or you know, any of your other initiatives?


Rich: I guess all of these are big questions and I think we need,
it’s back to that sort of point from Ana Lisa sort of balancing
the hope and expectation, I think we’re uniquely placed to
develop the evidence really clearly and one of the things that we
again think is so important is having this conversation in the
public about it and developing a shared view, almost you know, it
drives policy but it’s also something which I think the whole of
society needs to sort of think about how we address and what we
want to do collectively. I wouldn’t place it as a barrier but I
would highlight it as a strength that we’ve had and I think we’re
hopeful that we’ll continue is that long-term commitment in terms
of government and the NHS and I think that’s really powerful in
this space to maintain the UK’s position as being able to ask
these questions and to show that leadership.


Ana Lisa: And to bring together, we need to work really closely
across the ecosystem. So in my mind one of the challenges is if
one part is missing then that person is not going to get the
treatment and how we keep joining up these really important dots
across the whole ecosystem to make sure that most people will one
day be able to get a treatment.


Julia: And all those dots honestly, those dots can never even
start unless you have a diagnosis and it’s in time. And so there
are so many people around the world working on each of those dots
that connect a child or a patient to a treatment, but if you
can’t even be diagnosed or if you’re diagnosed too late, which is
what the reality is in the world of rare conditions right, then
you know, then it’s a little bit futile to race to a treatment or
even think if that’s possible. So I think the very, very first
thing is: can we find children and patients, like can we find
children like Mila in time? And I love hearing the word ‘hope’
that’s the word that keeps me going and doing what I’m doing
because if there isn’t any hope it’s pretty hard to keep
fighting, so I’m really glad, thank you both for having hope.


Okay, we’ll wrap up here. Thank you to Ana Lisa and to Rich for
joining me in this conversation today as we shed some light on
the challenges you know that those with rare conditions are
facing. We touched on the work being carried out across the
Genomics ecosystem in the UK to support those living with rare
conditions. If you’d like to hear more of this, please subscribe
to the G Word on your favourite podcast app. And thank you so
much for listening. I’ve been your host, Julia Vitarello. This
podcast was edited by Mark Kendrick at Ventoux Digital, and
produced by Naimah Callachand.