Cobbers on the Brain

What is Amyotrophic Lateral Sclerosis (ALS)?

A progressive neurological degenerative disease of the upper (UMN) and lower motor neurons (LMN). Upper motor neurons in the brain send messages to the lower motor neurons in the spinal cord then to a group of muscles or a single muscle.  In ALS, UMN and LMN start to stop sending messages to the muscles. Furthering to symptoms of: muscular atrophy, muscle stiffness, slurred speech, and difficulty swallowing.

This disease is currently incurable. Treatments available are to help control the symptoms and making living with ALS easier.

Medication: Rilutek helps reduce damage to motor neurons by decreasing glutamate levels. Many medications that directly treat the symptoms such as muscle cramps, stiffness, depression, and constipation are usually prescribed. Edaravone, just FDA approved in 2017, is a known antioxidant to help with ALS.

Therapy: Physical therapy that use very low-impact exercises can help with cardiovascular health, fight fatigue, and strengthen the muscles that are still unaffected. Speech therapy to help with speaking and help improve or continue the ability to communicate.

Support: Nutritional support allows for increased ease of eating food as well as increased nourishment to continue calorie intake. With a high calorie intake, they will not lose weight as fast thus slowing down the progression of weakness. Breathing support such as a mask or other machines. This support is vital due to the weakness of the respiratory system is the common way of passing.

Unfortunately, this disease is very deadly. Most people die from respiratory failure within 3-5 of first symptoms being present. Rilutek has been found to slow down the progression and increase life expectancy by a few months.  Breathing support has also shown to prolong survival.

Rare Case: Stephen Hawking

A short video about Stephen Hawking published by the Washington Post.

Most people don’t survive 3-5 years after diagnosis of ALS; however, one man beat the odds and survived 55 years with ALS.

Stephen Hawking was a renounced theoretical physicist from Oxford, England. Throughout his life he had worked on the basic laws of the universe. His contribution to society had won him awards from Presidential Medal of Freedom to CBE. While accomplishing our further understanding of the universe, battled with ALS. At the age of 21 (1964), Stephen Hawking was diagnosed with ALS. Progressing over the years he became wheelchair-bound and used a computerized voice system. Even through the progression, he did not allow the disease to limit him. Stephen was a very rare and unique case.

Hope for a brighter future:

A discovery of the NEK-1 gene. The function of NEK1: maintaining neuron’s cytoskeleton and regulation of the membrane of mitochondria. This gene has been found to be in sporadic and familial ALS posing an opportunity for a new target for drug development for ALS. *Further research is being conducted.

Therapeutic target for C9orf72-associated ALS. A common gene mutation, C9orf72, is a genetic cause of ALS. Inhibition of Spt4 protein, was found to reduce toxicity caused by C9orf72 repeat expansion. *Further research is being conducted.

AstroRx, stem cell-gene therapy Clinical trials are recruiting after positive results in animal models with ALS. In hopes that using human embryonic stem cells to produce astrocyte progenitor cells in labs will be effective. Injecting healthy astrocytes into the spinal canal of mice had shown a delay of onset. *New Clinical Trial is being conducted.

*For more information on stem-cell research.

Positive results for NurOwn stem cell phase II trial. Mesenchymal stem cells from bone marrow are being used for cell therapy. Administered intramuscular and intrathecal injection showed to be safe and highly tolerated. *Research being continued into phase III.

*For more information on the trial

A better understanding of ALS has begun to emerge and more quickly since the Ice Bucket Challenge. This challenge has risen awareness as well as enough money to put toward research. Through the ALS foundation and remarkable researchers, a cure for the incurable is reachable in the near future.

References:

The ALS Association

National Institute of Neurological Disorders and Stroke

Stephen Hawking

ALS, often known as Lou Gehrig’s disease, is a debilitating and horrific disease. It is defined as amyotrophic lateral sclerosis and is a neurodegenerative disease that affects nerve cells in the brain and spinal cord. In short, ALS targets motor neurons in the brain and spinal cord which causes them to deteriorate and eventually die, leading to loss of control of voluntary muscle movement. This is the main reason why ALS is so debilitating is because people with this disease eventually lose their ability to eat, breathe, move, and speak independently.

What I found most peculiar about this disease is the varying amount of knowledge that common people in our society have. It’s different than cancer or other more common diseases that seem to be a typical topic of conversation surrounding disease. With ALS, it seems to be that if you have a family member or person in your life who has been affected by ALS, then you know a lot about the disease and the difficult effects it has on a family. But, if that is not the case, it seems as thought people do not know too much about the specifics of the disease. This is an odd observation because ALS has been brought into the spotlight through the great Stephen Hawking, through movies, and social media, like “Tuesdays with Morrie”, and the Ice Bucket Challenge video phenomenon. When it is an encouraging sign that ALS is at least being talked about, the part that no one wants to talk about if almost always overlooked: the end.

End of life care with ALS is difficult for a few reasons. First, there is no set structure or correct drug to use to help. This is because the progression of ALS can vary from being quickly deteriorating or drawn out over many months. The ALS Association as well as many palliative care sites suggest the discussion of end of life care beginning as soon as they feel comfortable after the loved one has been diagnosed. In addition, they suggest to start hospice when the person has six months or less to live if the disease progresses as it has been. This conversation is not an easy one to have, but is highly encouraged to have earlier on in the disease so that the loved one can have a say in treatment, care, etc.

An interesting study was done a few years back where they had 50 caregivers complete a survey about ALS patients’ last month of life. Some of the study’s findings are listed below:

• Most common symptoms: difficulty communicating (62%), dyspnea (difficulty breathing) (56%), insomnia (42%), and discomfort other than pain (48%).
• They reported an advance directive (medical treatment, living will, etc) was completed by 88% of patients
• 2/3 of patients were enrolled in hospice
• Compared to nonhospice patients, hospice patients were significantly more likely to
  • 1) die in their preferred location
  • 2) die outside the hospital
  • 3) receive morphine

This study is not the only of its kind. Many scientists, psychologists, and sociologists alike are looking into analyses and reviews like this one to collaborate on how to better the end of life care for people with hospice. The study did conclude with saying that “many patients with ALS still experience distressing physical symptoms in the last month of life, despite enrollment in hospice.” It is gravely difficult to create a comforting setting for someone in their last month of living with ALS. However, hospice is a great option to get as close to comfort as they can.

So, what’s next? I think that the topic of ALS can be brought up more in science classes in secondary education and in conversations about societal diseases. Getting into the details of what the disease actually is is an important way to begin discussion of how to help those suffering and those caring for their loved ones who suffer.

As put beautifully by Morrie Schwartz about his life…

“The truth is, once you learn how to die, you learn how to live.”

For more information:

http://www.alsa.org/about-als/facts-you-should-know.html

http://www.alsa.org/about-als/what-is-als.html

http://n.neurology.org/content/59/3/428

Each day in the United States, about 15 individuals are diagnosed with a fatal motor neuron disease called ALS. This diagnosis is not one that can be lifted: ALS has no known cure. And after the physician mutters the three words “You have ALS,” the individual’s life is changed forever, their days become numbered, and they begin to ask themselves: What is going to happen to me?

What these individuals find out is terrifying, absolute, and unstoppable: ALS will lead to the death of voluntary muscles, and will take away:

• Their ability to move
• Their ability to speak
• Their ability to eat
   and finally…
• Their ability to breathe

But perhaps the most terrifying part about ALS is what it doesn’t take away: your brain.

Individuals diagnosed with ALS retain cognitive function. They are still there mentally, even if their bodies aren’t there physically. And with that information, I will leave you with some food for thought:

Could you imagine watching your body fade away? The effect that this would have on your loved ones? Being constantly aware that you have an expiration date, and that that date is quickly approaching?

I can’t even begin to fathom these feelings, but for over 20,000 individuals in America, these thoughts have become reality.

The Science behind ALS:

• ALS can be divided into two categories
  • Familial (fALS)
    • This form of ALS has an inheritable, or genetic, component.
    • It is likely the result of gene mutations that are inherited in an autosomal dominant fashion.
  • Sporadic (sALS)
    • This form of ALS has no known causes and occurs randomly.
      • Although not inherited, sporadic forms of ALS have also been linked to mutated genes

In addition to two main categories, there are also two main theories as to what is happening within the bodies of individuals living with ALS:

• oxidative stress → mitochondrial abnormalities → protein aggregation
  • This oxidative stress is likely the result of a mutation in the gene

    

    

    SOD1

    • SOD1 is needed to remove dangerous, unstable superoxide radicals that form in the body
    • When this gene is mutated, SOD1 is not able to remove these radicals, and they begin to accumulate within the cell, specifically within mitochondria
      • Soon after their formation, the SOD1 mutants will  get engulfed by healthy motor neurons and will:
        • build up within the cell, or aggregate together
        • cause the aggregation and improper folding of other necessary proteins within the body
        • lead to hyperactivation of the motor neuron, also known as excitotoxicity
          • induce motor neuron death
• RNA dysmetabolism
  • This is believed to be the result of an expanded GGGGCC (G4C2) repeat in the C9orf72 gene
    • This repeat is likely the cause of something known as an RNA gain-of-function mutation in which RNA post-transcriptional modifications are flawed and proper translation of RNA into proteins is unable to occur
    • As a result, RNA transcripts will begin to aggregate together, preventing the translation of proteins needed for the proper functioning of the voluntary muscles in the body.

      

      • • In ALS, specifically, these proteins will aggregate within motor neurons, leading to their death, subsequent muscle atrophy, and thus loss of motor function.

So what can you do to help?

• Raise Awareness
  • The link below is a calendar that was released during ALS awareness month in May that depicts 31 different ways that you can help raise awareness on ALS.
    • Just because it isn’t May doesn’t mean you can’t help raise awareness!
    • http://web.alsa.org/site/PageServer?pagename=AAM_calendar_PA
• Help Fund Research
  • This is a direct link to make donations to the ALS Foundation
    • Read about current research, and how your donation will be used
    • Learn how you can help support current and future ALS research
      • http://www.alsa.org/donate/
• Be kind, be understanding, and help those who can’t help themselves
  • Below is a link to an article giving helpful and meaningful tips to those who have recently been diagnosed with ALS
    • http://www.alsa.org/als-care/resources/publications-videos/factsheets/tips-for-newly-diagnosed.html

http://www.alsa.org/about-als/facts-you-should-know.html

https://www.ncbi.nlm.nih.gov/pubmed/27150074

https://journals.sagepub.com/doi/pdf/10.1177/1073858414561795

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3923493/

Stages of ALS

Overview of the ALS

Amyotrophic Lateral Sclerosis or ALS is a fatal disease that affects motor neurons. It is defined by the degeneration of upper and lower motor neurons, but the severity, symptoms, age of onset and cognitive deficits vary from case to case. Ultimately, respiratory failure due to the degeneration of the motor neurons is what causes the death of ALS patients.

What causes the development of ALS?

ALS is classified into two different sub-types: familial ALS (fALS) and sporadic ALS (sALS). The familial forms of ALS account for 10% of total ALS diagnoses and stems from inheritable, autosomal genetic mutations. It is usually characterized by having a family member with ALS as well. Sporadic ALS cases make up the remaining 90% of ALS diagnoses. These patients have no family history of ALS and there is no direct inheritance of a genetic mutation. The average age of onset for sporadic ALS is 56 which is about 10 years later than for familial ALS which is 45.7. These two sub-types of ALS are clinically the same but differ in how the genetic mutations develop. There are genetic mutations found in fALS that are also found in sALS which cause the motor neuron degeneration. However, the difference is the family history of the patient. 

For example, a mutation of the SOD1 gene is found in both fALS and sALS. SOD1 is an antioxidant enzyme that helps defend against Reactive Oxygen Species (ROS) that the cell produces. When there is a mutation in this enzyme, it leads to the oxidative stress that is found in the pathology of ALS. Oxidative stress also can cause  the unfolded protein aggregation that are found in the motor neurons of ALS patients.

The development of this disease can happen two different ways that are linked by common factors. Either oxidative stress and mitochondrial dysfunction cause changes in RNA metabolism leading to the motor neuron degeneration, or mutations in the proteins that bind RNA cause oxidative stress and mitochondrial dysfunction which also leads to motor neuron degeneration. The common links of these two different ways ALS can develop are the oxidative stress, RNA metabolism alteration and mitochondrial dysfunction. These ultimately cause the degeneration of the motor neurons by either protein aggregation, energy deficit or RNA dysfunction.

Caring for those with ALS

There are currently no treatments for ALS that can reverse the neurological damage that it causes. However, current medications aim at slowing the damage the disease causes and managing the pain the patient experiences. Breathing care is used to help patients breathe as their muscles become weaker. Physical therapy is also used to help with pain, walking and mobility to help the patient remain independent for as long as possible. Low-impact exercise is also used to maintain fitness and physical abilities. Other therapies used to manage the disease include occupational and speech therapy, nutritional support and psychological support.

In the late stage of ALS, most voluntary muscles are paralyzed (including those for breathing and swallowing). Patients in this stage usually require a ventilator for breathing and feeding tubes. The ALS association suggests hospice care for patients in the late stage of the disease. When patients received hospice care they were more likely to die in their preferred location (usually outside the hospital) and receive morphine. The final stage of ALS is the most physically and mentally distressing for the patient so it is important that their comfort level and desires are recognized.

What is ALS:

Amyotrophic lateral sclerosis, more commonly known as ALS, is a progressive neurogenerative disease that affects nerve cells in the brain and spinal cord that control your muscles. With ALS, motor neurons in your brain and spinal cord begin to break down and die. When this occurs, your brain is no longer able to send messages to your muscles. This lack of muscle movements causes your muscles to become very weak and muscle atrophy ensues. ALS is particularly difficult for the individual as though ones body may physically be deteriorating, they individual remains mentally sound.

Onset:

In the onset of ALS, the symptoms are often overlook or misread due to them being so subtle in the beginning. The earliest symptoms may include:

• Muscle weakness
• Muscle twitches (fasciculations)
• Cramps and/or tight and stiff muscles (spasticity)
• Muscle loss and/or atrophy
• Slurred and nasal speech
• Difficulty chewing and swallowing
• Excessive choking
• Excessive shortness of breath
• Unintended weight loss
• Hand or leg weakness
• Problems with balance or walking
• Fatigue
• Diminished musculature between forefinger and thumb.

These complaints develop into a more obvious weakness, atrophy, or rigidity that may cause a physician to suspect ALS. The part of the body that shows the earliest symptoms depends on which muscles are affected in that particular individual. Many first see the first effects in the hands or arms and experience difficulty with basic tasks that require manual dexterity (buttoning a shirt, writing, turning a key in a lock). In other people symptoms can initially affect the legs. This can lead to awkwardness when walking or running or notice more frequent tripping to stumbling. When these symptoms first occur in the arms or legs, this is referred to as “limb onset” ALS. Other individual can notice their first changes in their voice and speech, spasms in muscle of the face, jaw, voice box, throat, tongue, and inappropriate, excessive laughing or crying. This is referred to as “bulbar onset” ALS.

Most people that develop ALS are between the ages of 40 and 70, with an average of age 55 with a diagnosis. ALS is 20% more common in men and your risk becomes higher as you age.

Treatment:

Like in neurological diseases, treatment cannot reverse damages that had already occurred, however, we can treat symptoms in an attempt to make lives for comfortable for those affected. Various drugs such as Riluzole, Edaravone, can help to slow the progression of the diseases. Individuals can also partake in various therapies such as breathing care, physical therapy, occupational therapy, speech therapy, and nutritional support.

End of Life Care:

End of life care becomes a relevant topic during late stage of this disease. Late stage is characterized by most voluntary muscles becoming paralyzed, including those used for breathing and swallowing. During this stage, a feeding tube or a ventilator are often necessary. Hospice is often recommended during this final stage of progression. This stage of life can be very painful causing many to be prescribed morphine. This is where the idea of physician assisted suicide becomes a very relevant topic of conversation.

http://alsworldwide.org/care-and-support/article/early-symptoms-of-als-mnd
http://www.alsa.org/about-als/facts-you-should-know.html

ALS, or amyotrophic lateral sclerosis, is a neurodegenerative disease that affects neurons in the brain and spinal cord. This disease is characterized by muscle atrophy, as the neurons that signal and control the muscles are targeted for degeneration. This causes sclerosis, which is scarring or hardening of tissue. The disease is typically diagnosed between ages 40 and 70. There are two types of ALS: sporadic and familial.

• • • • Sporadic: most common form of ALS; can affect anyone
      • Familial: accounts for 5-10% of all cases of ALS; inherited disease

Symptoms of ALS get worse over time and there is currently no cure for the disease. Most people diagnosed with ALS die about 3-5 years after diagnosis, often from respiratory failure. Common symptoms of ALS include:

• • • • Fasciculations, or muscle twitches
      • Muscle cramps
      • Tight/stiff muscles, or spasticity
      • Muscle weakness
      • Slurred speech
      • Difficulty chewing and swallowing

As the disease progresses, individuals may experience difficulty moving, speaking or forming words, and breathing, as well as difficulty with some mental processes. As there is no cure for ALS currently, it is treated mostly to control and slow down symptoms. Treatment is mostly provided by supportive care to keep individuals as mobile and comfortable as possible. Medication, physical therapy, speech therapy, nutritional support, and breathing support are some of the specific treatments available. Despite all of these treatments, the disease can only be slowed down so much.

Due to the fast progression of the disease, much of the focus of ALS is on end-of-life care. There is a large controversy about how to handle this disease toward the end of someone’s life, what treatments should be done, and who should be able to make final decisions during that time. Some of the biggest questions surrounding this topic include:

• • • • Hospice
      • Physician-assisted suicide
      • Decisions at end-of-life

The discussion surrounding hospice is whether or not it is right to stop curing/treating the illness, as well as who decides whether or not the individual should enter hospice care. Hospice is meant for when the illness can no longer be cured and the individual has 6 months or less to live. Hospice is meant to keep the patient comfortable and only provide relief for the symptoms. It is difficult for many individuals to accept that there is no further treatment, that they have less than 6 months to live, and that they will have to spend the rest of their life without any control until they die. This leads to the controversy with physician-assisted suicide. Many people believe that a person diagnosed with ALS should be able to choose this option toward the end of their life in order to stop them uncontrollably watching themselves losing motor control and slowly dying. The main reason for supporting this decision is to avoid pain and suffering, leave the world with dignity and peace, and reduce health care costs. However, others believe that there should be no reason for anyone to choose to die and that it is selfish to choose this option when they have a family or other people in their lives. It is also an argument that people near death should not be responsible for making the decision to take their own life. Many people see physician-assisted suicide as breaking the oath a doctor takes to preserve lives and increasing the value of human life. Finally, the question about who is expected to make the decisions toward an individual’s end of life is often controversial. It is based on a thin line between whether or not the diagnosed individual is able to make their own decision or if the family must make final decisions for them. 

All of these issues create difficult conversations when dealing with ALS and causes struggles when deciding treatment plans for individuals after diagnosis. In order to provide the best care for patients, it is important to keep the patient’s wants and needs as a priority and make decisions based off of what is best for the patient and the remainder of their life.

http://www.alsa.org/about-als/what-is-als.html

https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Fact-Sheets/Amyotrophic-Lateral-Sclerosis-ALS-Fact-Sheet

https://www.lawteacher.net/free-law-essays/medical-law/physician-assisted-suicide-one-of-the-most-controversial-topics-law-medical-essay.php

Marijuana is found in many cultures around the world. People in India used it in ancient times for its medicinal properties. The Rastafari religion in Jamaica promotes cannabis for religious uses. In the United States it has been used illegally for recreational purposes for years and now it is being used at an increasing rate as a medical treatment to some health problems. What is going on in marijuana?

CBD vs. THC

The two main active chemicals in marijuana are Cannabidiol (CBD) and Tetrahydrocannabinol (THC). They are nearly identical to each other in chemical structure with each having 21 carbons, 30 hydrogens, and 2 oxygens. As you can see in the picture below, the only difference is how an oxygen is bound. So if they are so similar in structure, shouldn’t they do the same things?

https://medium.com/cbd-origin/cbd-vs-thc-the-difference-explained-b3cfc1da52f0

That answer is no. These two molecules are different in the ways that they bind to Cannabinoid Receptors. There are two different types of Cannabinoid Receptors: CB1 and CB2. CB1 is primarily found in the brain and in the central nervous system whereas CB2 is mostly found in peripheral organs and the immune system. CBD and THC both bind to the CB2 receptor enabling them to make changes to the immune system and these peripheral organs. But, THC binds to CB1 in the brain causing psychoactive effects like “getting high”. CBD does not bind to CB1 and can actually negate the bond between CB1 and THC, neutralizing the psychoactive effects.

So many companies and states have started using CBD oil as a beneficial product to help boost the immune system of individuals. This also keeps large concentrations of THC out of the brains of these people. That being said, medical marijuana with both THC and CBD are still in use.

Medical Usage states

Medical marijuana has been legalized in 33 States and recreational marijuana has been legalized in 10 states, below is a map of these “green states”. Marijuana has been used to treat migraines, anxiety, cancer, obesity, and general pain.

https://medicalmarijuana.procon.org/view.resource.php?resourceID=000881

Reasons for Hesitation

So if using marijuana as a medical drug can be so helpful to our society, what makes people not want this to happen everywhere?

THC that binds to the CB1 receptors in the brain causes psychoactive effects. One part of the brain that these receptors are very prevalent in is the hippocampus, the hub for memory. With chronic use of marijuana, there is a possibility for long-term effects on the memories of those using.

Another reason is the lack of parameters to police usage. With alcohol, we have a clear limit of how much can be in your blood before you are impaired to drive. With THC it is harder to test, and THC can stay in the body for much longer making the test less accurate.

Conclusion

As I am writing this blog, marijuana is still classified as a Schedule I drug by federal law. This makes it very difficult to obtain marijuana to do research to find scientific evidence of more uses of marijuana. Many people think that we could more easily find a middle ground for marijuana if it were lowered to a Schedule II or Schedule III drug. Along with this we could do more research to possibly make it even better as a medicine and potentially less dangerous.