ALS i

What is ALS?

Vienna Tiessen
bio/chem 11
Ms. Weiss and Ms. Oamen
June 5th, 2020
 ALS 1

ALS

Disease is a constant worry that we all must face in our daily lives, a
looming fear and unfortunate frequency. Incurable and ongoing diseases
affect around 133 million Americans alone and is thought to increase to 157
million, with around 81 million having multiple conditions. The focus of this
presentation is ALS standing for Amyotrophic Lateral Sclerosis. Uncovering
this complex disease, the impacts on the brain and how medication can
help are some of the mysteries that are answered here.

Amyotrophic Lateral Sclerosis gradually paralyzes people due to the

brain’s inability to communicate with the muscles in the body. Over time,
the muscles start to deteriorate, causing a person to lose the ability to walk,
talk, eat, swallow and eventually breath. Alongside these complications,
they also may develop painful neuropathy, meaning
nerve disease or damage. ALS is caused by the death of
motor neurons (picture to the right) which are nerve cells
extending from the brain to the spinal cord, and all
through the body. Motor neurons initiate and provide vital
communication links between the brain and muscles.
When the loss of breathing becomes effective, the
person will depend on a ventilator (picture to the
left). Although they lose most of their motor
ability, they still retain higher mental processes
like remembering, understanding, and problem
solving. This in turn allows more awareness that
they are losing function, and depression or
anxiety may develop. People who have ALS burn calories faster and tend
to lose weight at fast speeds, that can lead to malnourishment. There is not
one type of ALS, the most common one being Sporadic, which means it
can affect everyone regardless of age or gender.The second type is
Familia, which means it
ALS 2

can be passed from parent to child. Around 5-10% of all cases are Familia.
No matter the type of ALS, 30% of all people with it form something that is
referred to as Bulbar ALS. In early stages, motor neurons in the
corticobulbar of the brainstem are affected first leading to the muscles in
the head, face and neck to be paralyzed first. Around 90% of people have
sporadic type ALS which means that there is no clear reason as to why the
disease has developed. ALS diagnosis’ are mainly based on detailed
history of symptoms and signs observed by a physician during physical
examination and multiple tests to rule out similar diseases. Symptoms
include muscle twitches in the arm, leg, shoulder or tongue, muscle
cramps, tight and still muscles, muscle weakness that affects the arm, leg,
neck or diaphragm, slurred and nasal speech, and difficulty chewing or
swallowing.When symptoms begin in the arms or kegs it is referred to as
“limb onset” others that first notice speech or swallowing are referred to as
“bulbar onset.” It takes around 9-12 months to be diagnosed from the time
that symptoms are noticed. ALS is not contagious, there is no cure for it
and few treatment options making it 100% fatal. Some ways to treat it
include medication, physical and speech therapy and nutritional and
breathing support. Approximately 80% who have ALS die within 2-5 years
of diagnosis. Over 200,000 around the world have ALS and around 3,000
of those being Canadians. Around 1,000 Canadians die from it per year
which is similar to the amount that get diagnosed with it per year. Although
it attacks both genders, it affects males more than females. It is not fully
known what the cause of ALS is but researchers think it could be a
combination of genetics and environmental triggers but are studying
exposure to toxic substances, diet and physical trauma as potential causes
for ALS.
 The U.S food and drug administration (FDA) has only approved two
drugs that slow down ALS. They are Riluzole and Edaravone. Riluzole
(picture to the right) extends survival by a few months, while Edaravone
improves daily function. Riluzole does not reverse the nerve damage or
muscle weakness, it works by protecting the nerves in the brain and spinal
cord from natural substances. These are called Glutamate and are thought
to be part of the reason to cause nerve damage. It is taken orally and on an
empty stomach every 12 hours. It can come in pill or liquid form which can
lead to dizziness, lightheadedness, tiredness, drowsiness, nausea,
vomiting, diarrhea, loss of appetite, stomach pain and numbness/ tingling
around the mouth. Edaravone (picture to the left) relieves
effects of Oxidative stress that could be related to the
death of motor neurons. People can be allergic to this
drug causing hives, itching, trouble breathing, swelling in
the face and throat or lightheadedness. It is given through
an injection in the vein by a healthcare provider and is
usually a 28-day treatment. The common side effects of
Edaravone include bruising, headache or trouble walking. New research
may be able to change the limited treatment methods, as scientists have
uncovered a gene that could be used for a new drug target. The gene is
called STMN2, its full name being Stathmin2, which has the gene type of
protein coding. It encodes a member of the Stathmin family of
phosphoproteins (a protein containing phosphorus), and plays a regulatory
role in neuronal growth. STMN2 is necessary for normal axon outgrowth
and regeneration. After peripheral nerve injury, axons readily regenerate.
The distal portion of the axon, which is the long threadlike part of a nerve
cell, is disconnected from the cell body and undergoes wallerian
degeneration. Wallerian degeneration is the biochemical changes that
occur in axons. Post-transitional stabilization of STMN2 rescued neurite
outgrowth and axon regeneration deficits induced by TDP-43 depletion.
Neurite outgrowth is when developments produce new projections as they
grow in response to guidance cues. TARDBP, better known as TDP-43 is a
DNA-binding protein. Restoring STMN2 expression warrants examination
as a therapeutic strategy for ALS.

ALS 4

ALS damages the neurons in part of the brain that is responsible for
cognition and behavior. Messages from the motor neurons, called upper
and lower, are transmitted in the spinal cord and motor nuclei then to a
particular muscle. Scientists have now proven that ALS affects more than
just the motor cortex. A practicing neurologist by the name of Sanjay Kalra
says “ ALS was previously thought to be a disease restricted to the motor
system causing only weakness but a significant portion of people with ALS
also have cognitive and behavioral changes. We wanted to know how ALS
was impacting other parts of the brain to cause these symptoms” (Kalra,
2011). Kalra uses MRI scans
(picture to the left) of the brain to
measure various chemicals. He
recently looked at two chemicals
called NAA and mlns. NAA is a
“neural marker” meaning it is only
found in neurons, and levels of
mlns increase where there is abnormal scarring in the brain. "If NAA is
decreased, it means neurons have died or they are not working. Many
papers have shown NAA to be decreased in regions where you expect it to
be decreased with ALS -- the motor cortex. But our recent study shows that
these levels are also decreasing in areas of the brain responsible for
cognition and behaviour," says Kalra. As he mentioned, ALS not only
affects muscle movement but also behavior and thinking. Around 50% will
experience some change in cognitive ability or behavior, ranging from
minor symptoms to full-blown dementia.
Some behavioral changes include:
● Embarrassing, childish, inappropriate or uncharacteristic behavior
● Focus on eating one type of food, especially sweets
● Loss of manners
● Lack of basic hygiene
● Lack of judgment in decision-making
● Inability to concentrate or shift focus
● Lack of concern to others and themselves
● Being fixated on a single idea or activity and repeating it a lot
● Increased aggression
● Saying no when they mean yes and vice versa
● Writing or speaking in the wrong order, not making sense
● Losing ability to spell
● Forgetting the meanings of words
● Able to think of the word they want to say but unable to say it
● Inability to follow simple instructions
● Difficulty remembering what they intended to do

ALS is a fatal disease that breaks down muscles over time and
eventually kills its victim. This paper was interesting and hard to research,
as I have seen these effects first hand on my uncle, who was taken from
me due to ALS. It was unique to learn and fully understand the inner
workings of the disease, and I hope that I was able to shed some light on
this truly complex illness.
 ALS 6

References

       

“ALS: A New Therapy May Be in Sight.” Medical News Today, MediLexicon International,
www.medicalnewstoday.com/articles/324212​.

“Amyotrophic Lateral Sclerosis (ALS) Fact Sheet.” National Institute of Neurological Disorders
and Stroke, U.S. Department of Health and Human Services,
www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Fact-Sheets/Amyotrophic-Lateral-Scl
erosis-ALS-Fact-Sheet​.

“Ask the Doc: Q & A with Edward Kasarskis, MD, PhD.” The ALS Association,
web.alsa.org/site/PageServer?pagename=ALSA_Ask_January2014​.

“Changes in Thinking & Emotional Lability.” ALS Texas,

www.alstexas.org/navigating-als/for-patients/changes-thinking-emotional-lability/​.

“Changes in Thinking & Emotional Lability.” ALS Texas,

www.alstexas.org/navigating-als/for-patients/changes-thinking-emotional-lability/​.

“Edaravone Uses, Side Effects & Warnings.” Drugs.com,

www.drugs.com/mtm/edaravone.html#:~:text=Edaravone​ works by relieving the,to treat
amyotrophic lateral sclerosis.

Henderson, Wendy. “16 Fast Facts About ALS.” ALS News Today, 28 Apr. 2017,
alsnewstoday.com/2017/04/28/fast-facts-about-als/​.

Huebner, Eric A, and Stephen M Strittmatter. “Axon Regeneration in the Peripheral and Central
Nervous Systems.” Results and Problems in Cell Differentiation, U.S. National Library of
Medicine, 2009, ​www.ncbi.nlm.nih.gov/pmc/articles/PMC2846285/#:~:text=After​ peripheral
nerve injury, axons,by glial cells, predominantly macrophages.
 ALS 7

Koza P;Beroun A;Konopka A;Górkiewicz T;Bijoch L;Torres JC;Bulska E;Knapska E;Kaczmarek

L;Konopka W; “Neuronal TDP-43 Depletion Affects Activity-Dependent Plasticity.” Neurobiology
of Disease, U.S. National Library of Medicine, ​pubmed.ncbi.nlm.nih.gov/31176717/#:~:text=TAR
DNA-binding protein 43,abnormally phosphorylated and ubiquitinated aggregates.

“MRI Research Demonstrates ALS Attacks Multiple Parts of the Brain.” ScienceDaily,
ScienceDaily, 17 Sept. 2011, ​www.sciencedaily.com/releases/2011/09/110916131252.htm​.

“Riluzole Oral : Uses, Side Effects, Interactions, Pictures, Warnings & Dosing.” WebMD,
WebMD, ​www.webmd.com/drugs/2/drug-12138/riluzole-oral/details#:~:text=Riluzole​ is thought
to work,the cause of nerve damage.

“STMN2 Stathmin 2 [Homo Sapiens (Human)] - Gene - NCBI.” National Center for
Biotechnology Information, U.S. National Library of Medicine,
www.ncbi.nlm.nih.gov/gene/11075​.

“Wallerian Degeneration.” Wallerian Degeneration - an Overview | ScienceDirect Topics,

www.sciencedirect.com/topics/neuroscience/wallerian-degeneration#:~:text=Wallerian
degeneration refers to the,microenvironment supportive of axonal regeneration.

“What Is ALS?” ALS Society of Canada, 6 Feb. 2019, ​www.als.ca/about-als/what-is-als/​.