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