Last week, my neurochemistry class studied the debilitating neurodegenerative disease amyotrophic lateral sclerosis (ALS). Throughout the week, we dove deeply into the neurochemical mechanisms behind ALS, namely the interacting roles that reactive oxygen species and ineffective RNA metabolism play in the development of the disease.
According to current research, chronic oxidative stress (and the resulting reactive oxygen species produced by mitochondria) can lead to the aggregation of RNA binding proteins like FUS and TDP43 in the cytoplasm. Aggregation of these proteins can eventually lead to their loss of function, which can have dangerous effects due to the concomitant sequestration of chaperone proteins. With the loss of chaperone proteins, the body struggles to properly fold proteins that aid in responding to oxidative stress.
Interestingly, the relationship appears to be reciprocal, as RNA dysmetabolism can also cause oxidative stress and accompanying mitochondrial damage. In this proposal, when the FUS and TDP43 proteins are mutated or sequestered in the cytoplasm, the cell loses key anti-oxidative stress pathways. In the case of TDP43 loss of function, the cell experiences gene transcription from an activated family of FOXO transcription factors that leads to mitochondrial damage.
And while the science was captivating and essential to our understanding of ALS, when it came to our end of the week debriefing, science didn’t carry the conversation. Instead, the ethical considerations associated with end of life care in ALS took center stage.
Reflecting now, I think we arrived at this topic from our discussions on the lack of treatments for ALS. To our knowledge, there is just one well-accepted drug, called Rilutek, that slows the disease progression in some people. The lack of options for treating ALS amazed me and filled me with sadness. It ultimately drove home the inevitability for many people stricken with ALS of being trapped inside one’s own body. This happens because of a disconnect between mind and body where mind isn’t the issue. Instead, the motor neurons in the spinal cord are destroyed whilst sparing the neurons in the brain.
To our class, this maintenance of mental capacity throughout the disease raised important questions about a patient’s wishes at the end of life. Since they are mentally capable, should a suffering ALS patient have the right to end his or her life through physician assisted suicide? One student even held the opinion that after a patient dropped below a certain quality of life, their insurance should increase as to cover the exorbitant costs of maintaining someone’s life.
In the end, what we were all struggling to decide was the best option for both the patient and family. ALS certainly presents a unique situation because unlike other debilitating diseases, these patients retain their mind and personality and even take pleasure from seeing their loved ones and communicating with them. Yet, when the disease reaches such an advanced stage where speech is impossible, breathing is difficult, and someone’s individuality is gone, who benefits then? I agreed with many of my classmates that if they or a family member were in this position, they would want a quick and peaceful ending. However, I had second thoughts this past weekend after reading about technologies that enable late-stage ALS patients to communicate.
The study was published in the Journal of Neural Engineering and involved research into a new brain-computer interface (BCI) technology. The researchers built off of the fact that current BCI technology isn’t effective for ALS because the current systems depend on brain processes that are impaired in ALS. That’s why the new technology targeted a different area of the brain called the precuneus, which is located in the parietal cortex. This brain area is associated with consciousness and is not affected in patients with ALS. The study was small and only involved two patients, but the results were exciting. The researchers trained the two patients to self-regulate two types of brain waves, theta and gamma, in the precuneus. With their ability to activate either brain wave on command, the patients could answer questions and participate in simple conversation.
Technologies like this truly demonstrate the need for science and could one-day help ALS patients maintain relationships with their children and grandchildren. Yet, part of me is still saddened that previously vibrant individuals could be confined to the equivalent of a yes or no answer.
Despite the 40 minutes of discussion my class spent on the topic, I’m still on the fence. I think this mental struggle on my part is a testament to the difficulty of the problem but demonstrates the importance and need for these discussions to take place. With no signs of a game-changing therapeutic approach to ALS coming soon, we need to thoroughly consider what good we are doing by extending the lives of ALS patients indefinitely. Who knows, we may realize that our healthy intentions have taken us in the wrong direction.
Perspectives on ALS End of Life Care
