0:00:07.138,0:00:11.691
In 1963, a 21-year-old physicist [br]named Stephen Hawking

0:00:11.691,0:00:14.869
was diagnosed with a rare[br]neuromuscular disorder

0:00:14.869,0:00:19.589
called amyotrophic lateral sclerosis, [br]or ALS.

0:00:19.589,0:00:22.018
Gradually, he lost the ability to walk,

0:00:22.018,0:00:23.328
use his hands,

0:00:23.328,0:00:24.737
move his face,

0:00:24.737,0:00:26.760
and even swallow.

0:00:26.760,0:00:29.856
But throughout it all,[br]he retained his incredible intellect,

0:00:29.856,0:00:32.267
and in the more[br]than 50 years that followed,

0:00:32.267,0:00:36.829
Hawking became one of history’s most [br]accomplished and famous physicists.

0:00:36.829,0:00:39.458
However, his condition went uncured

0:00:39.458,0:00:44.279
and he passed away in 2018 [br]at the age of 76.

0:00:44.279,0:00:46.049
Decades after his diagnosis,

0:00:46.049,0:00:49.078
ALS still ranks as one [br]of the most complex,

0:00:49.078,0:00:50.279
mysterious,

0:00:50.279,0:00:53.918
and devastating [br]diseases to affect humankind.

0:00:53.918,0:00:57.868
Also called motor neuron disease [br]and Lou Gehrig’s Disease,

0:00:57.868,0:01:03.440
ALS affects about two out of every[br]100,000 people worldwide.

0:01:03.440,0:01:05.450
When a person has ALS,

0:01:05.450,0:01:06.769
their motor neurons,

0:01:06.769,0:01:11.018
the cells responsible for all voluntary [br]muscle control in the body,

0:01:11.018,0:01:13.050
lose function and die.

0:01:13.050,0:01:16.695
No one knows exactly why[br]or how these cells die

0:01:16.695,0:01:20.360
and that’s part of what [br]makes ALS so hard to treat.

0:01:20.360,0:01:22.436
In about 90% of cases,

0:01:22.436,0:01:26.520
the disease arises suddenly, [br]with no apparent cause.

0:01:26.520,0:01:29.378
The remaining 10% of cases are hereditary,

0:01:29.378,0:01:34.909
where a mother or father with ALS passes [br]on a mutated gene to their child.

0:01:34.909,0:01:38.595
The symptoms typically first appear [br]after age 40.

0:01:38.595,0:01:43.626
But in some rare cases, like Hawking’s,[br]ALS starts earlier in life.

0:01:43.626,0:01:49.625
Hawking’s case was also a medical marvel [br]because of how long he lived with ALS.

0:01:49.625,0:01:55.194
After diagnosis, most people with [br]the disease live between 2 to 5 years

0:01:55.194,0:02:00.101
before ALS leads to respiratory problems [br]that usually cause death.

0:02:00.101,0:02:04.115
What wasn’t unusual in Hawking’s case[br]was that his ability to learn,

0:02:04.115,0:02:04.955
think,

0:02:04.955,0:02:08.076
and perceive with his senses [br]remained intact.

0:02:08.076,0:02:12.405
Most people with ALS do not experience[br]impaired cognition.

0:02:12.405,0:02:16.005
With so much at stake [br]for the 120,000 people

0:02:16.005,0:02:18.396
who are diagnosed with ALS annually,

0:02:18.396,0:02:22.036
curing the disease has become one of [br]our most important scientific

0:02:22.036,0:02:23.876
and medical challenges.

0:02:23.876,0:02:25.716
Despite the many unknowns,

0:02:25.716,0:02:31.036
we do have some insight into how ALS [br]impacts the neuromuscular system.

0:02:31.036,0:02:36.085
ALS affects two types of nerve cells [br]called the upper and lower motor neurons.

0:02:36.085,0:02:39.024
In a healthy body, [br]the upper motor neurons,

0:02:39.024,0:02:40.923
which sit in the brain’s cortex,

0:02:40.923,0:02:44.464
transmit messages[br]from the brain to the lower motor neurons,

0:02:44.464,0:02:46.435
situated in the spinal cord.

0:02:46.435,0:02:49.875
Those neurons then transmit [br]the message into muscle fibers,

0:02:49.875,0:02:52.836
which contract or relax in response,

0:02:52.836,0:02:54.778
resulting in motion.

0:02:54.778,0:02:57.235
Every voluntary move we make occurs

0:02:57.235,0:03:00.736
because of messages transmitted [br]along this pathway.

0:03:00.736,0:03:03.997
But when motor neurons degenerate in ALS,

0:03:03.997,0:03:06.976
their ability to transfer [br]messages is disrupted,

0:03:06.976,0:03:10.777
and that vital signaling system [br]is thrown into chaos.

0:03:10.777,0:03:14.146
Without their regular cues, [br]the muscles waste away.

0:03:14.146,0:03:17.073
Precisely what makes [br]the motor neurons degenerate

0:03:17.073,0:03:19.961
is the prevailing [br]mystery of ALS.

0:03:19.961,0:03:24.529
In hereditary cases, parents pass genetic [br]mutations on to their children.

0:03:24.529,0:03:27.761
Even then, ALS involves multiple genes

0:03:27.761,0:03:31.132
with multiple possible impacts [br]on motor neurons,

0:03:31.132,0:03:34.121
making the precise triggers[br]hard to pinpoint.

0:03:34.121,0:03:38.832
When ALS arises sporadically,[br]the list of possible causes grows:

0:03:38.832,0:03:39.640
toxins,

0:03:39.640,0:03:40.472
viruses,

0:03:40.472,0:03:41.273
lifestyle,

0:03:41.273,0:03:45.191
or other environmental factors [br]may all play roles.

0:03:45.191,0:03:47.540
And because there are [br]so many elements involved,

0:03:47.540,0:03:53.399
there’s currently no single test that[br]can determine whether someone has ALS.

0:03:53.399,0:03:57.480
Nevertheless, our hypotheses [br]on the causes are developing.

0:03:57.480,0:04:01.772
One prevailing idea is that certain[br]proteins inside the motor neurons

0:04:01.772,0:04:03.641
aren’t folding correctly,

0:04:03.641,0:04:05.730
and are instead forming clumps.

0:04:05.730,0:04:10.491
The misfolded proteins and clumps [br]may spread from cell to cell.

0:04:10.491,0:04:13.471
This could be clogging up normal[br]cellular processes,

0:04:13.471,0:04:17.551
like energy and protein production, [br]which keep cells alive.

0:04:17.551,0:04:21.291
We’ve also learned that along with [br]motor neurons and muscle fibers,

0:04:21.291,0:04:24.350
ALS could involve other[br]cell types.

0:04:24.350,0:04:29.161
ALS patients typically have inflammation [br]in their brains and spinal cords.

0:04:29.161,0:04:34.280
Defective immune cells may also play [br]a role in killing motor neurons.

0:04:34.280,0:04:38.352
And ALS seems to change the[br]behavior of specific cells

0:04:38.352,0:04:41.031
that provide support for neurons.

0:04:41.031,0:04:43.923
These factors highlight [br]the disease’s complexity,

0:04:43.923,0:04:47.961
but they may also give us a fuller[br]understanding of how it works,

0:04:47.961,0:04:50.130
opening up new avenues for treatment.

0:04:50.130,0:04:54.142
And while that may be gradual,[br]we’re making progress all the time.

0:04:54.142,0:04:56.280
We’re currently developing new drugs,

0:04:56.280,0:04:59.231
new stem cell therapies [br]to repair damaged cells,

0:04:59.231,0:05:03.591
and new gene therapies [br]to slow the advancement of the disease.

0:05:03.591,0:05:06.041
With our growing arsenal of knowledge,

0:05:06.041,0:05:09.002
we look forward to discoveries[br]that can change the future

0:05:09.002,0:05:11.011
for people living with ALS.