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How 6 Rare Diseases Are Changing Everyday Medicine

January 14, 2020

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more. [♩ INTRO] Individually, rare diseases are… rare. In the US, we usually say that a disease is
rare when it affects fewer than 200,000 people
in the whole country. And in the EU, a disease is rare when it affects fewer than one out of every
2000 people. That’s not very often. But because there are so many different rare
diseases experts estimate there are about 7000 collectively, it’s not so rare to have a
rare disease. In fact, about 30 million Americans have a
rare disease, around the same number who have type 2 diabetes! So, studying them is important in it’s own
right. But these sorts of investigations can also
reveal larger insights into how our bodies work. And because many rare diseases are caused
by relatively simple, known mechanisms, they can also tell us about the things that can go wrong in much
more common diseases. Sometimes, this even means researchers can
come up with a drug that works for millions of people. Here are six times research into the most
uncommon maladies on the planet have turned out the benefit the masses. First up, a bone mineralization disorder called
hypophosphatasia, or HPP. In severe cases, which affect about one in
every 100,000 people, patients have soft bones that can easily break
and deform. Many patients are in chronic pain and often
lose teeth prematurely, and a quarter experience more than 10 fractures
in their lifetime. The disease is caused by a gene mutation that
prevents the body from making correct versions of the
enzyme alkaline phosphatase. In the mid-1960s, researchers learned that
this enzyme regulates the body’s production of a molecule
called pyrophosphate. It’s found in blood and urine and prevents the main mineral in our bones
from growing. Without enough of the enzyme, the body has
too much pyrophosphate, so mineralization doesn’t happen as well. While researchers were working to understand
HPP, they realized that pyrophosphate might actually
have another use, too. Previously, they’d found that this molecule
had a perk: It kept bone minerals from dissolving. So maybe it could help patients with osteoporosis, a disease of low bone mass that affects 200
million people around the world. Scientists then searched for compounds that
mimicked pyrophosphate, and they found that the water softening molecule
bisphosphonate did the trick. Now, it’s a common osteoporosis drug although they later realized this treatment
actually works for a different reason: It prevents cells called osteoclasts from
breaking down bone. Because they don’t need extra pyrophosphate,
artificial or otherwise, the drug that HPP patients helped give the
world won’t help them and might even make them worse. But if nothing else, it did change how much
we know about bone biology and led to a whole new class of drugs for
millions of people. Next is Gaucher disease, which affects somewhere around one in every
50,000 or 100,000 people and shares some interesting parallels to Parkinson’s. Guacher is what’s known as a lysosomal storage
disease, which means there’s a defect in the organelle in cells (lysosomes) that
digests garbage. When that happens, the lysosomes can’t get
rid of the trash fast enough, and it builds up. In Gaucher, this is the result of an enzyme
deficiency, specifically one called glucocerebrosidase. It specializes in breaking down certain glycolipids, which are basically fats with a sugar attached
to them. So without enough of the enzyme, they build
up, especially in the liver, spleen, and bone
marrow, which produces blood cells. As a result, people with the disease often
don’t have enough blood cells, which can make them tired and more prone to
bruising and bleeding. They can also get enlarged spleens and livers. On rare occasions, Gaucher patients also develop
symptoms ike tremors and slow movements similar to Parkinson’s, a neurodegenerative disorder that famously
affects people’s ability to move. Initially, scientists didn’t make much of
this. Then, they noticed something surprising with
the relatives of Gaucher patients. Those who carried the mutation that causes
the enzyme deficiency were more likely to get Parkinson’s, too. In fact, a huge genetic study in 2009 revealed
that around 7% of participants with Parkinson’s
had a mutation in that gene the most for any single gene. In genetics, a finding like that for a multi-factorial disease like Parkinson’s
is huge. Now, scientists are working to figure out
what it means. One possibility is that not having enough
of that enzyme prevents cells from breaking down alpha-synuclein
proteins. These can get misfolded in the brain and are thought to be one of the main causes
of Parkinson’s. That’s unlikely to be the whole story, but it could be important for a subset of
cases. Scientists are hopeful that studying this
enzyme and lysosomes in general may lead to a new
understanding of Parkinson’s, and possibly to new treatments for the disease, and for those with Gaucher, too. But the fact that Gaucher has already helped identify the biggest genetic risk factor to the second-most common neurodegenerative
disease is a pretty big deal. Speaking of lysosomal storage diseases as you do scientists are finding that another one, called Niemann-Pick, might help us combat
Ebola virus. Technically, and fortunately, Ebola hemorrhagic
fever is also a rare disease. But that could change at any time with an
outbreak. Back in 2011, researchers were studying the
virus to figure out how it was getting into cells. They knew it used a certain glycoprotein to
do it, but they didn’t know what on our cells it
was targeting. So, they set up a screen, testing the Ebola
glycoprotein on a series of different cells, each of which
had one mutation. Weirdly, a bunch of the cells that kept the
virus out had a mutation in a gene called NPC1, which makes a protein that helps shuttle cholesterol
around inside cells. This is the same gene that’s mutated in
Niemann-Pick disease type C, or NPC, which affects around one in 150,000 people. Patients with it end up with build-ups of
cholesterol inside neurons, which can cause dementia at a shockingly early
age. For that reason, it’s sometimes called ‘childhood
Alzheimer’s.’ Thankfully, there are some treatments for
it, but the disease itself could also help treat
thousands of others. Because when scientists tried to infect cells
from NPC patients with Ebola… they couldn’t. The mutation was keeping Ebola out. The fact that Ebola targets NPC1 explains
part of why it’s so deadly it’s in all cells, so the virus can target
any cell of the body, not just a few like most viruses. Now, researchers are using this knowledge
to create new Ebola drugs. If they can make molecules that block the
NPC1 protein, they may be able to prevent people from getting
infected. Sometimes, rare diseases are helpful to scientists because they can confirm that what they’ve
seen in lab animals also applies to humans. That’s what happened with an extremely rare
condition called congenital leptin deficiency. As the name implies, people with the disease
don’t make enough leptin, a hormone that fat cells produce to tell the
body to stop eating. As a result, they’re constantly hungry and
eat way too much food. These people become obese very early in life, usually within months of being born. We know of about 30 cases now, but for a long
time, we didn’t know the condition existed. And that became important because for decades, scientists have been using a mouse with mutations
in its leptin genes to study type 2 diabetes. The mice become very obese, and if they have
the right genetic background, they develop diabetes quickly, making it easier
to study the disease in the lab. Years of mice experiments suggested that leptin
might be important for our understanding of obesity. But no one was really sure how relevant it
was to people. That changed in 1997, when researchers identified
two severely obese children who shared the same mutation in their leptin
genes. They made far less leptin than normal, showing that this hormone was a key player
in how our bodies regulate the amount of food we eat and how much fat
we put on. Like with Niemman-Pick and Ebola, some rare
diseases, it turns out, come with perks. In the case of something called Laron syndrome, those advantages are potentially life-changing
for the rest of us if we can figure out how to mimic them. People with Laron’s are very short under 1.4 meters tall because of a mutant growth hormone receptor. Even though they make plenty of growth hormone, their bodies can’t use it normally, so they never get very tall and their limbs
are short. It’s a unique form of dwarfism, and fewer than 400 cases have been diagnosed
worldwide. The surprising thing is, even though these
people are often obese, they have normal blood pressure, and they seem impervious diabetes and cancer. In one village in Ecuador where the condition
is common, just one person in a sample of 99 was diagnosed
with cancer. In contrast, cancer kills about 20% of the relatives of
people with Laron syndrome. The secret, both to their disease and their
superpowers, may have to do with something called insulin-like
growth factor 1, or IGF-1. For those with Laron’s, growth hormone receptors don’t trigger cells
to make IGF-1. And since that’s what tells the body to
grow, not having it around explains their short
stature. But IGF-1 is also thought to contribute to
uncontrolled growth in some cancers, so limiting it in adults might be a good idea. So far, scientists have even found that mice missing the growth hormone receptors
make less IGF-1 and live longer and are less diseased. Now, they’re working on ways to get the
same results with a pill or supplement. Finally, if going cancer and diabetes-free
isn’t enough, there’s a rare blood clotting disease that’s
revealing a lot about aging, too. In plasminogen activator inhibitor type 1
deficiency, patients lack a specific blood clotting protein, so clots break down faster than they should. Which obviously isn’t great. But last year, scientists studying an Amish
community in Indiana, where the condition is more common, found that carriers of the disease live abnormally
long, around 10 years longer than their peers. They also have fewer cases of diabetes. These carriers make less of the protein than
normal, but fortunately don’t have any problems
with clotting. It’s still preliminary, but researchers
in Japan are now testing a therapy that partially blocks the clotting protein. If it works, it could be an amazing outcome
of studying something that affects just a few hundred people. Digging into rare diseases doesn’t seem
to make a lot of sense if you’re trying to do the most good for
the most people. But as these examples show, because of our
shared biology, it’s often remarkable what we can learn. It’s been the spark behind osteoporosis
drugs, a key part of our understanding of Parkinson’s, and might even let us live longer, healthier
lives. So, so far, our knowledge about these rare
conditions looks like it’s giving back many times over. So, we’re trying something a little different
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  • Reply SciShow July 15, 2018 at 9:24 pm

    To get 2 months of unlimited access to Skillshare for free, click here:

  • Reply Jesse Hickman January 5, 2020 at 5:34 am

    Bran?!?!?! WTF!!! Wut sense does that make?

  • Reply Kirsten T January 5, 2020 at 10:21 pm

    Can you talk about the idea of not locking out your knees in order to prevent fainting? …people say this all the time when you’re standing for an extended period of time and this cannot be true. If it is, why?

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