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In 1963, a 21-year-old physicist 
named Stephen Hawking

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was diagnosed with a rare
neuromuscular disorder

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called amyotrophic lateral sclerosis, 
or ALS.

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Gradually, he lost the ability to walk,

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use his hands,

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move his face,

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and even swallow.

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But throughout it all,
he retained his incredible intellect,

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and in the more
than 50 years that followed,

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Hawking became one of history’s most 
accomplished and famous physicists.

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However, his condition went uncured

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and he passed away in 2018 
at the age of 76.

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Decades after his diagnosis,

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ALS still ranks as one 
of the most complex,

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mysterious,

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and devastating 
diseases to affect humankind.

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Also called motor neuron disease 
and Lou Gehrig’s Disease,

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ALS affects about two out of every
100,000 people worldwide.

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When a person has ALS,

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their motor neurons,

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the cells responsible for all voluntary 
muscle control in the body,

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lose function and die.

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No one knows exactly why
or how these cells die

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and that’s part of what 
makes ALS so hard to treat.

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In about 90% of cases,

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the disease arises suddenly, 
with no apparent cause.

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The remaining 10% of cases are hereditary,

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where a mother or father with ALS passes 
on a mutated gene to their child.

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The symptoms typically first appear 
after age 40.

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But in some rare cases, like Hawking’s,
ALS starts earlier in life.

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Hawking’s case was also a medical marvel 
because of how long he lived with ALS.

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After diagnosis, most people with 
the disease live between 2 to 5 years

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before ALS leads to respiratory problems 
that usually cause death.

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What wasn’t unusual in Hawking’s case
was that his ability to learn,

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think,

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and perceive with his senses 
remained intact.

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Most people with ALS do not experience
impaired cognition.

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With so much at stake 
for the 120,000 people

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who are diagnosed with ALS annually,

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curing the disease has become one of 
our most important scientific

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and medical challenges.

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Despite the many unknowns,

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we do have some insight into how ALS 
impacts the neuromuscular system.

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ALS affects two types of nerve cells 
called the upper and lower motor neurons.

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In a healthy body, 
the upper motor neurons,

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which sit in the brain’s cortex,

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transmit messages
from the brain to the lower motor neurons,

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situated in the spinal cord.

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Those neurons then transmit 
the message into muscle fibers,

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which contract or relax in response,

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resulting in motion.

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Every voluntary move we make occurs

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because of messages transmitted 
along this pathway.

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But when motor neurons degenerate in ALS,

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their ability to transfer 
messages is disrupted,

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and that vital signaling system 
is thrown into chaos.

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Without their regular cues, 
the muscles waste away.

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Precisely what makes 
the motor neurons degenerate

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is the prevailing 
mystery of ALS.

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In hereditary cases, parents pass genetic 
mutations on to their children.

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Even then, ALS involves multiple genes

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with multiple possible impacts 
on motor neurons,

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making the precise triggers
hard to pinpoint.

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When ALS arises sporadically,
the list of possible causes grows:

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toxins,

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viruses,

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lifestyle,

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or other environmental factors 
may all play roles.

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And because there are 
so many elements involved,

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there’s currently no single test that
can determine whether someone has ALS.

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Nevertheless, our hypotheses 
on the causes are developing.

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One prevailing idea is that certain
proteins inside the motor neurons

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aren’t folding correctly,

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and are instead forming clumps.

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The misfolded proteins and clumps 
may spread from cell to cell.

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This could be clogging up normal
cellular processes,

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like energy and protein production, 
which keep cells alive.

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We’ve also learned that along with 
motor neurons and muscle fibers,

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ALS could involve other
cell types.

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ALS patients typically have inflammation 
in their brains and spinal cords.

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Defective immune cells may also play 
a role in killing motor neurons.

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And ALS seems to change the
behavior of specific cells

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that provide support for neurons.

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These factors highlight 
the disease’s complexity,

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but they may also give us a fuller
understanding of how it works,

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opening up new avenues for treatment.

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And while that may be gradual,
we’re making progress all the time.

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We’re currently developing new drugs,

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new stem cell therapies 
to repair damaged cells,

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and new gene therapies 
to slow the advancement of the disease.

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With our growing arsenal of knowledge,

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we look forward to discoveries
that can change the future

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for people living with ALS.