Why is it so hard to cure ALS Fernando G. Vieira
In 1963, a 21-year-old physicist
named Stephen Hawking
was diagnosed with a rare
neuromuscular disorder
called amyotrophic lateral sclerosis,
or ALS.
Gradually, he lost the ability to walk,
use his hands,
move his face,
and even swallow.
But throughout it all,
he retained his incredible intellect,
and in the more
than 50 years that followed,
Hawking became one of history’s most
accomplished and famous physicists.
However, his condition went uncured
and he passed away in 2018
at the age of 76.
Decades after his diagnosis,
ALS still ranks as one
of the most complex,
mysterious,
and devastating
diseases to affect humankind.
Also called motor neuron disease
and Lou Gehrig’s Disease,
ALS affects about two out of every
100,000 people worldwide.
When a person has ALS,
their motor neurons,
the cells responsible for all voluntary
muscle control in the body,
lose function and die.
No one knows exactly why
or how these cells die
and that’s part of what
makes ALS so hard to treat.
In about 90% of cases,
the disease arises suddenly,
with no apparent cause.
The remaining 10% of cases are hereditary,
where a mother or father with ALS passes
on a mutated gene to their child.
The symptoms typically first appear
after age 40.
But in some rare cases, like Hawking’s,
ALS starts earlier in life.
Hawking’s case was also a medical marvel
because of how long he lived with ALS.
After diagnosis, most people with
the disease live between 2 to 5 years
before ALS leads to respiratory problems
that usually cause death.
What wasn’t unusual in Hawking’s case
was that his ability to learn,
think,
and perceive with his senses
remained intact.
Most people with ALS do not experience
impaired cognition.
With so much at stake
for the 120,000 people
who are diagnosed with ALS annually,
curing the disease has become one of
our most important scientific
and medical challenges.
Despite the many unknowns,
we do have some insight into how ALS
impacts the neuromuscular system.
ALS affects two types of nerve cells
called the upper and lower motor neurons.
In a healthy body,
the upper motor neurons,
which sit in the brain’s cortex,
transmit messages
from the brain to the lower motor neurons,
situated in the spinal cord.
Those neurons then transmit
the message into muscle fibers,
which contract or relax in response,
resulting in motion.
Every voluntary move we make occurs
because of messages transmitted
along this pathway.
But when motor neurons degenerate in ALS,
their ability to transfer
messages is disrupted,
and that vital signaling system
is thrown into chaos.
Without their regular cues,
the muscles waste away.
Precisely what makes
the motor neurons degenerate
is the prevailing
mystery of ALS.
In hereditary cases, parents pass genetic
mutations on to their children.
Even then, ALS involves multiple genes
with multiple possible impacts
on motor neurons,
making the precise triggers
hard to pinpoint.
When ALS arises sporadically,
the list of possible causes grows:
toxins,
viruses,
lifestyle,
or other environmental factors
may all play roles.
And because there are
so many elements involved,
there’s currently no single test that
can determine whether someone has ALS.
Nevertheless, our hypotheses
on the causes are developing.
One prevailing idea is that certain
proteins inside the motor neurons
aren’t folding correctly,
and are instead forming clumps.
The misfolded proteins and clumps
may spread from cell to cell.
This could be clogging up normal
cellular processes,
like energy and protein production,
which keep cells alive.
We’ve also learned that along with
motor neurons and muscle fibers,
ALS could involve other
cell types.
ALS patients typically have inflammation
in their brains and spinal cords.
Defective immune cells may also play
a role in killing motor neurons.
And ALS seems to change the
behavior of specific cells
that provide support for neurons.
These factors highlight
the disease’s complexity,
but they may also give us a fuller
understanding of how it works,
opening up new avenues for treatment.
And while that may be gradual,
we’re making progress all the time.
We’re currently developing new drugs,
new stem cell therapies
to repair damaged cells,
and new gene therapies
to slow the advancement of the disease.
With our growing arsenal of knowledge,
we look forward to discoveries
that can change the future
for people living with ALS.