VO: Sickle-cell disease is one of the most prevalent genetic conditions worldwide.
AMBROISE WONKAM: Every single year we have at least 300,000 newborns born with sickle-cell disease.
VO: The condition can cause sudden pain, as well as long-term joint and organ damage, frequent infections, and anemia.
JIMI OLAGHERE: You can tell a sickle-cell patient by just shaking their pocket, and if you hear pills dangling in
there you know this guy has chronic, chronic pain.
VO: Treatments are limited and the only curative solution, a stem cell transplant, is not available to everyone with sickle cell.
But new treatments are being trialled that could offer hope of a life without symptoms to people with the condition,
and they work through gene editing.
HAYDAR FRANGOUL: If we can improve the lives of patients with sickle-cell disease we are not only keeping them away from the hospital
we are actually allowing them to go to school, to go to work, to be with their families.
I would not be heartbroken to see my floor have not a single patient with sickle-cell disease having any complications related to it.
JIMI: You have to try and lead a normal life as much as possible but then you have this chip on your
shoulder that’s sickle cell that literally affects every single decision you make, every single
thing, like when you wake up, how you wake up, what you eat for breakfast, if you can go to work,
if you could take care of your kid.
VO: Over 6 million people are living with sickle-cell disease worldwide,
three-quarters of them in sub-Saharan Africa.
AMBROISE: Every single year we have at least 300,000
newborns born with sickle-cell disease and 80 percent of these children are born in Africa.
VO: Around five percent of the world's population carries trait genes for haemoglobin disorders,
but that figure rises as high as 25 percent in some regions.
Two parents carrying sickle-cell trait have a one in four chance of having a child with sickle-cell disease.
JIMI: I was first diagnosed with sickle cell at birth. I was fortunate enough to have parents
to bring me to the United States to do the amniocentesis test, of course they both knew
they had the sickle-cell trait, both my parents are Nigerian, uh living in Nigeria at the time.
Growing up, it was tough. Um I actually even, I don't remember my first crisis but I have
a reminder. I have this little deformed, uh, finger that doesn't grow as quick or didn't grow with the
rest of my fingers that was actually my first crisis that it was so bad that it caused tissue
damage and that's why that finger didn't grow like the rest of them.
VO: Pain is the most common symptom of sickle-cell disease.
As sickle cells travel through small blood vessels they can get stuck and clog blood flow causing what are known as pain crises.
JIMI: It was almost a revolving door every week, in and out of the hospital, just trying to keep my head above water.
AMBROISE: For the past 111 years where we know sickle-cell disease exists, we unfortunately have only four medications that have been approved by the
FDA and hydroxyurea is the only one that is widely available, but unfortunately not always accessible
in patients in Africa for example. So most of the case patient will be treated symptomatically for
pain, will be treated symptomatically for anemia. will be treated symptomatically for recurring
infection without a definitive treatment.
JIMI: I've tried the lot.
I did hydroxyurea, at one point I did um, frequent blood transfusions as well - that helped for a while
then I did hydration therapy where it wasn't blood transfusions because they were worried my iron levels were getting too high
so you know what we're just gonna flush you with liquids every Tuesday.
VO: Until recently the only curative treatment for sickle-cell disease was a stem cell transplant,
but this comes with its own risks and requires a bone marrow donor who is a close match to the recipient.
But now new treatments are being developed that could allow anyone with sickle-cell
disease to lead a symptom-free life.
HAYDAR: We are currently treating patients with sickle-cell disease and beta thalassemia using a innovative therapy called CRISPR-Cas9 gene editing.
VO: CRISPR-Cas9 is an enzyme that can be targeted to make specific cuts in a cell's DNA.
HAYDAR: And this gene editing is used to target a specific gene to allow the stem cells in those patients to produce
high levels of fetal haemoglobin.
VO: Sickle cell is caused by a genetic mutation.
AMBROISE: Sickle-cell disease is due to a single nucleotide change
that alter the structure of haemoglobin, and haemoglobin is the protein that made of 70 percent of red blood cell.
VO: Normally haemoglobin floats freely within a healthy red blood cell transporting oxygen around
the body. But in sickle-cell disease the structure of haemoglobin is altered.
Now after releasing oxygen to cells, the mutated haemoglobin locks together, causing the shape
of the red blood cell to change from a pliable donut to a more rigid, stickier, sickle shape.
Researchers are beginning to trial using CRISPR to directly edit the sickle cell mutation
but Haydar Frangoul’s group are trying something different.
HAYDAR: Interestingly, throughout evolution, babies in utero make high amounts of fetal haemoglobin. Fetal haemoglobin is very efficient
in transporting oxygen. When babies are born they switch from making fetal haemoglobin
to making adult haemoglobin which is haemoglobin A. Haemoglobin A in the situation of sickle cell
patients has a mutation in it. In utero babies do not experience any sickle cell crisis or
complications related to their disease and what we know is we know that this BC11A
gene is what is making that switch, think about it as a switch.
VO: BCL11A tells your stem cells to stop producing fetal haemoglobin.
By targeting it with CRISPR this treatment switches fetal haemoglobin production back on.
HAYDAR: We know for a fact that patients with sickle-cell disease for example who have persistent high fetal haemoglobin
and there are populations specifically in western Africa and in Saudi Arabia that persist to have high levels of fetal haemoglobin,
and those patients do not experience significant complications related to their sickle-cell disease
and some of them are completely asymptomatic. So what we are trying to do is we are trying to
make the cells make high number of fetal haemoglobin and that fetal haemoglobin
can stabilize the red blood cell and prevent it from sickling.
VO: And this trial is already showing exciting results for people like Jimi.
He had his stem cells harvested, gene edited with CRISPR, and re-implanted back into his body where they started producing fetal haemoglobin.
JIMI: The outcome of this new treatment for me has been a miracle.
It was about a week maybe a week and change, I, I could feel it, instantly, I could feel the lack of pain,
I felt, woah okay there's no pain, and usually because I'm attached to the bed this throughout this whole period,
usually once a day I'll buzz my nurse to help me out with pain medication and she'll
bring something and I didn't need that anymore, all of a sudden I didn't need pain medication I,
I wanted to get up. Um, one of the weirdest things, my eyes, usually because of sickle cell you
break down a lot of red blood cells and then it shows in your eyes with the bilirubin and your
eyes become yellow. My eyes became white. Just like pure white, which was of course I love that,
I've always wanted white eyes but it was just a shock to me, I couldn't believe it, I had to
keep on like "is this... is this me?"
HAYDAR: The seven patients that received this treatment
all have benefited from it and have not experienced any sickle-cell related complications after the treatment.
VO: This treatment can't repair damage that sickle-cell disease has already caused, but it could prevent new problems from even arising.
Unfortunately it's very expensive.
Transporting an individualized therapy like this from a trial setting to where it is needed most
around the world will be an enormous challenge.
HAYDAR: My hope is if we show that this treatment works, and the preliminary data is very exciting,
that I'm hoping that this therapy over time will be able to scaled up to treat patients all over the world, as a scientist working with this therapy
this is my goal, is to help every patient affected with sickle-cell disease in the future.
VO: Ambroise Wonkam is optimistic that this technology could be used across the globe but he also knows
there is more to be done with the treatments we already have.
AMBROISE: We know things that works for now for sickle-cell disease is newborn screening and that newborn screening needs to be accompanied by
comprehensive care embedded in specialized center for sickle-cell disease. We know
those simple public health intervention works and those are the first thing to do, but it doesn't
mean that we should not add a curative alternative for sickle-cell disease. So the future of gene
editing I do think have a place in low resources setting, specifically if we find a way to make them
technologically accessible, cheaper, and safer.
JIMI: I love this poem by Walt Whitman, Pioneers! O Pioneers! Uh, that's one of my favorite poems ever,
and I just feel like a pioneer. I don't mind being the guinea pig - in fact I relish this role, so i'm happy that i got this opportunity.
My thing is i just want to make sure that everyone gets this opportunity as well, that's my biggest thing is
this is should be released as soon as possible and it should be affordable and it should be global.