How 6 Rare Diseases Are Changing Everyday Medicine


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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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100 thoughts on “How 6 Rare Diseases Are Changing Everyday Medicine

  1. These advancements are amazing, but I take the opportunity to remind people that although they are good options they are not easy for the patients. Bisphosphonates do wonderful things but have absolutely terrible side effects including severe gastric bleeding and not being able to eat or drink , nor lie down for hours either side of taking them. They can also cause horrific bone pain.

  2. how would the ecosystem look with out Predators ever existing and evolving? I think it's a interesting question to ask.

  3. Clickbait was a virus that spreaded long before this channel existed..
    Its so ancient that the virus spreaded to over a thousand channels now

  4. Can you do a vedio on congenital spyndolatheses an other congenital bone defects an maybe even its relationsh to early onset degenerative disk disease ?

  5. so basically removing IGF-1 will stop growing humans to unnecessary size while increasing lifespan?
    the movie akira instantly comes to mind. old young people.

  6. I love this channel. I learn something new everyday. I love learning about health, new medications, and new treatments

  7. The study about Leptin and the Mice was referenced in a passage on the July 7th MCAT… Hope I don't get dinged for discussing test material 🙁

  8. It should be mentioned that the first thing on the list didn't have the intended positive benefit. The problem caused by osteoporosis is that your bones become weaker, more likely to break, as a result of the larger air pockets in them. Drugs like Osteobiflex fulfill the symptom of light bones by stopping the osteoclasts and making them denser, but that doesn't lead to healthier bones, nor make the bones less likely to suffer a fracture or break.

    Osteoclasts are important members of your team, along with the osteoblasts that build the bone. Simply preventing them from doing their job is like building a house and, instead of leveling out the ground through excavation to reveal the compacted earth that's good for building on, you just start building right on the top soil. And building and building, only adding, never subtracting, and it becomes like this awful game of stacking stones.

    Still cool that they found something out from the rare disease though, and hopefully they can put it to better use in the future. (Thumbs up for video)

  9. Please support public funding of scientific research! When our budgets get slashed, it is these kinds of breakthroughs that slip through the cracks.

  10. I got skillshare. Thanks. I'm trying a class on adobe premier pro for 2018. Hopefull making my videos much better. also gonna try a bunch of arts and design classes.

  11. Immediately signed up to skillshare, two months free is not to be sniffed at.

    Also I appreciate the explanation of the new sponsorship thing, changing the business model of scishow a bit to include sponsorship must have been a difficult decision. I'm not generally opposed to sponsorship because as far as I can tell it generally allows people who make good things to make great things (or in this case, continue making great things), which I think is the part we should focus on.

    Thanks Hank et. al. for keeping me informed and entertained

  12. You don't get to invent the light bulb from looking at a candle.

    By being too focused on a specific problem, it's easy to end up running in circles. Other horizons must be explored to find new ways to solve a problem.

  13. Update on Bisphosphonate treatment — Unfortunately osteoclasts and osteoblasts have complimentary roles in bone maintenance. When bisposphonate inhibits the bone osteoclasts from their dissolving and restructuring role while the osteoblasts continue their bone formation function it is the equivalent of resurfacing a road without the preparatory step of grinding out the cracks and stabilizing the substructure of the road bed, where needed, before the new top coat. This in practice then actually causes more bone fractures and fragility. The bone density appears to be increased, but the occurrence of catastrophic fracturing is higher than in untreated osteoporosis patients.

  14. I kinda loved this video! It was interesting, dynamic, expressive & most importantly informative to the minute detail! I'm digging the gusto!

  15. I once made an account on playstation I named Ebola that way whenever I got a kill online that persons screen would say "you were killed by Ebola"

  16. Justin Y. vs van Hendrix vs Master Therion

    Where can I get the infectious disease of having every comment liked a thousand times?

  17. Ah, good ol IGF. I remember doing a mock project that focused on that and how it can be a possible target for stopping abnormal cell growth. Watching this video has me wishing that I finished that project now.

  18. Most of the smartest peoples including me agrees that the biggest threat to humanity are not nukes, asteroid or even an AI the biggest threat is that on a some sunny day a deadly plague will spread on earth and it would wipe out all the 8 billion peoples on earth or can even make them zombie we got to prepare for such situation and the thing that can protect the humanity from this extinction threat from diseases is having a insurance of humanity on mars.
    #best wishes John Greens' best friend.

  19. Hey could I get some help? A few friends of mine watched this video on how Lettuce is plastic and synthetic and now won't go near the stuff. Here is the video: https://youtu.be/4bk7X38V7dc

  20. The greatest gift the older generation can give the younger generation is to die. I am a member of older generation FYI. Imagine if all the generational negativity lasted for 50 more years, such as calling millennials narcissistic and entitled blah blah blah. Until people can learn not to bully amd denigrate others and stop destroying the planet we don't deserve to live longer

  21. I have a rare autoimmune disease called mast cell activation syndrome, I’m hoping I can get my doctors on board with studying me during my pregnancy because there’s not much research or information on people with mast cell disorders who become pregnant

  22. According to the book the compas of pleasure, actually lepton production is not the problem most of the time, but lepton insensibility, patients don't have enough receptors for lepton so they keep eating.

  23. best feeling when you randomly find out about stuff you didn't even know existed, every morning on your pocket supercomputer, laptop, or smart display.

  24. SciShow is one of this one’s longest-subscribed channels on Youtube – high quality in production values (audio is particularly appreciated), and high quality content. Far more likely to trust SciShow than some of the clickbait alternatives out there. Live long and upload often.

  25. Support your friendly neighborhood Zebras by researching Ehler-danlos syndrome! It's a rare condition that needs a lot more awareness, and in-depth studies done on how to better treat it.

  26. Fascinating as always.

    Chronic Illnesses & diseases are a personal interest of mine, partially because they're intriguing, but primarily 'cause I have the neurological disease Fibromyalgia. It's not a rare condition, with it affecting approximately one in every twenty people (in western countries), or about 5-7% of the population. Despite this, it hasn't had a great deal of funding being put into research, with the majority of studies concerning it being pilot studies using very small groups of people.

    It's etiology has remained elusive, though in recent years it has been clarified to be a both a neurological & neuroendocrine disease (it was previously considered a rheumatoid condition due the heightened presence of several pro-inflammatory cytokines), through improved fMRI techniques. That it overlaps multiple medical disciplines has proved to be a hindrance to both scientific research & clinical treatment – though treatments like Lyrica/Ketamine for the Neuropathic Pain, Cymbalta for the "Fibro-fog", Naproxen for the inflammation & hormone treatments for the HPA Axis dysfunctions have certainly reduced the symptoms, and increased the quality-of-life for sufferers.

    Definitive research into the specific genes that cause Fibromyalgia have been sadly lacking (it's been known that it is a hereditary condition since at least the 1990s – especially in people with Mediterranean ancestry). With it occurring in such a significant percentage of the population, there is the implication (thanks to evolutionary genetics) that the mutation causing it has improved the survivability of people in the distant past. Why it would cause such a myriad of terrible symptoms in people living today is a puzzle – one that perhaps would also lead to advances in research that could benefit people with other illnesses, like those you mention in this video.

  27. I’d love to see a video on rare diseases with neat backstories. Not necessarily ones that are helping find cures for other diseases, but more ones with other interesting stories to them. For example, I live with CRPS type II, a rare degenerative neurological disorder. Except it doesn’t attack the Central Nervous System directly. Nope, it likes to destroy the Sympathetic Nervous System, which is how the most common form of the disease (now known as CRPS type I) got its original name of Reflex Sympathetic Dystrophy. CRPS type II, on the other hand, was actually the first form identified and it was originally known as Causalgia. And it’s the history of Causalgia where things get interesting. It was discovered during the American Civil War. Yet, despite its initial discovery and the craziness that followed (they tried to amputate effected limbs which failed miserably), there are still no approved treatments for it in the vast majority of countries.

    It’s cause is also very interesting. It’s triggered by some form of trauma to the body (the severity of the trauma involved draws the line between the two types). Type I, which accounts for 90% of patients, can be caused by something as minor as a stubbed toe and it’s onset can be delayed by up to several weeks. Yet when the disease finally starts, it starts instantly, straight into the deep end with excruciating, nearly intractable pain. A rather common story amongst patients is, “yeah, I broke a small bone and everything was fine. Then a few weeks later, I woke in the middle of the night, screaming in agony because the sheet was touching me.” Despite this overly dramatic onset, it still takes an average of 6 years to get diagnosed.

    Both forms of CRPS combined are rather rare, with 1 in 5,000 people thought to have them. (For reference, in the US, rare is fewer than 1 in 2,000 people.) But CRPSs claim to fame isn’t its scarcity. Rather, it’s the symptoms. It’s the most painful chronic illness known to science. On a 50pt scale, a broken bone is about a 20, severe spinal problems are a 30-40, cutting off half your foot with a lawnmower is a 41, and CRPS is a 43. It usually effects only 1 or 2 limbs, but it can spread to effect all extremities and some patients even have it in their abdomen, plus it can damage internal organs (usually the heart).

    Other common and interesting symptoms include changes in skin color to white, red, blue, or purple (I even turn polka dotted, which is super entertaining) often accompanied by changes in skin temperature, muscle spasms, muscle atrophy, involuntary movements, osteoporosis, edema, hyperalgesia, and severe allodynia. That’s on top of the pain of feeling like you’ve been dipped in gasoline and lit on fire, your bones being crushed with a pickaxe, and/or the feeling of being wrapped in barbed wire.

  28. Absolutely loved this show! Huge huge fan of DFTBA and this one specially needs to be said out loud in scientific community so that we are not asked to do the kind of research which will have direct relevance

  29. I have PAI-1 it sucks having this bleeding disorder i have had it since i was 5 years old it took 3 years to be diagnosed with PAI-1 i have to be very careful of the things i do everyday if i get a bruise i have to take this medicine to help me to clot a small cut can bleed for up to 15 minutes.

  30. So, do you think we'll get leptin therapy for obesity some day? Something that actually works would be awesome.

  31. I have a rare disease, Glanzmann’s thrombasthenia. Last time I checked it affected about one in one million people. Understanding it lead to the development of glycoprotein IIb/IIIa inhibitors, a powerful class of antiplatelet drugs.

  32. What rare disease do YOU have?

    I have Marfan Syndrome, the genetic disorder Michael Phelps was reported to have. (He doesn't, as it is a pretty debilitating disorder – at least if you are a question mark whose only superpower is beating the "are your arms as long as an Orangutan" game at the zoo, as I am.)

  33. I have the most common "Rare" genetic disease that hardly no one knows about (I've had people in the medical community give me false information about it), and that is Hemochromatosis, or commonly called Iron Overload Disease. I've 2 different mutated Genes which causes me to absorb Far more Iron than I need, which builds up in your body and becomes Toxic, particularly to various organs. The only way to get rid of Iron in your body is to Bleed (you lose a very small amount through skin and intestine cell flaking). Because women have a menstruation cycle it is overwhelmingly a Male disease, it usually shows up in Women after menopause.

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