Disease/Hot topics

The True ALS Challenge

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The ALS Ice Bucket Challenge has flooded social media outlets in the last few months and created a buzz around this neurodegenerative disease. It has jumped to the forefront of charitable causes, overshadowing many big organizations like the American Cancer Society.
But how much do people really know about ALS? I have watched dozens of videos of friends who have dowsed themselves in frigid water and pledged to donate to the ALS foundation to contribute to the cause. However, if anyone asked me what ‘ALS’ stood for or the effects of the disease two weeks ago, I wouldn’t be able to answer. I had no idea that about 15 people are diagnosed every day with Amyotrophic Lateral Sclerosis. I also learned that ALS, commonly known as Lou Gehrig’s Disease, mainly affects Caucasian males between the ages of 40 and 70.[1] Also, the majority of cases occur because of sporadic gene mutations. The next diagnosis could easily be a parent, a professor, a coworker, or a neighbor.
This great act of charity has raised a lot of money quickly, but where is that money going? The true results of these awareness campaigns lie in research trials that eventually lead to potential drug treatments. ALS is a frightening disease that decreases muscle function until the lungs and heart stop functioning. All the while, the person maintains their cognitive abilities. Research focuses on finding ways to decrease the extent and rate of motor function loss associated with the disease.
The one drug treatment available for ALS, Riluzole, is an antiglutamatergic drug. It acts by inhibiting the voltage-gated ion channel NMDA and reduces release of the neurotransmitter glutamate. As promising as this is, the exact mechanism of action is unknown. In the review article, the role of the glutamate acting on the NMDA receptor is discussed in detail. The grounds for this research are founded by evidence of high levels of glutamate in the plasma and cerebral spinal fluid of ALS patients as well as the toxic role NMDA plays in leading to cell death. The research focuses on glutamate’s excitatory actions in the spinal cord.

NMDA activation: https://www.youtube.com/watch?v=Q_z5ZL9STMw  
Overexcitation of a cell by glutamate may lead to a number of pathways that lead to the same end result, cell death. One mechanism involves the endoplasmic reticulum (ER), the organelle responsible for modifying proteins into their functional form. Overactive NMDA receptors increase ER stress which depletes Ca2+ stores. Without proper balance of this ions ER cannot function properly which leads to improper folding of important proteins. This may have a connection to a common mutation in ALS patients found on the SOD-1 protein where it is not folded into its functional form.
Cell death from increased Ca2+ levels is more likely to occur when it is transported by over-active NMDA receptors than other receptor types. A similar toxic effect to ER stress is found in the mitochondria which produces reactive oxidative species during the oxidative production of ATP. These, along with numerous other pathways, link glutamate to the physiological effects of ALS. Because the only drug for ALS targets the glutamate-NMDA interaction and the contribution of NMDA in cell destruction, there is no denying its implications for possible drug treatments for the disease.
The real task is not completing the ALS Ice Bucket Challenge within 24 hours. It’s planting the seed of interest to the general public and pursuing that with ample research. If we use the Ice Bucket Challenge as a platform for discussion on this topic, then a wider audience may be reached and informed about this disease. I have discussed one area that is currently being examined for therapeutic purposes for ALS.  I would like people to step away from the camera, and begin to dig deeper into the topic. To question where research is headed for ALS treatment. Without the ALS Ice Bucket Challenge as an attention grabber, I may not have had the opportunity to learn as much as I did and to share the most recent research. Continue to stay informed on the direction of research and keep on the lookout for the positive outcome of the ALS campaign in the future.

[1] http://www.alsa.org/about-als/who-gets-als.html
Link to article mentioned: http://www.sciencedirect.com/science/article/pii/S0925443912002736
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I Challenge You to Learn About ALS and the Ice Buket Challenge

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The neurodegenerative disease, amyotrophic lateral sclerosis (ALS), has been the center of YouTube videos and Facebook feeds for the past few months. It has been brought to focus by the Ice Bucket Challenge, which was created by Pete Frates, a victim of ALS. The challenge includes pouring ice water on oneself after being challenged. If you do not complete this challenge within twenty-four hours, the person is supposed to donate money to the ALS Association. Before we get into a brief view of the science behind ALS, here are some of my favorite Ice Bucket Challenge Videos.
Shay Carl Ice Bucket Challenge
Benedict Cumberbatch Ice Bucket Challenge
Before the Ice Bucket Challenge, most people knew ALS as Lou Gehrig’s Disease. I knew it as that and didn’t know much about the disease until the challenge and reading an article about ALS. Those with ALS have massive loss of motor neurons in the central nervous system, which includes the brain steam, spinal cord, and cerebral cortex. Symptoms include muscle weakness, muscle wasting, and muscle spasticity. These usually result in issues with breathing, swallowing, and speaking. Eventually, a person will lose the ability to control their body. Most ALS patients die within three to five years after diagnosis. While the disease can be inherited, it is usually sporadic.

The article that my neurochemistry class read described research focusing on possible causes of ALS. I will highlight three possible causes that were mentioned. The first is glutamate toxicity. This means that glutamate, a neurotransmitter, is exciting the receptor too much. This result is neurons like motor neurons being destroyed. Another possible cause is a mutation of the SOD1 gene. This SOD1 gene allows for the SOD1 protein to be made. Think of SOD1 as a police officer who protects cells from dangerous toxins. When the SOD1 gene is mutated, the protein can’t do its job properly. It starts to collect in the cell and can cause cells to destroy themselves. The last possible cause of ALS that I”ll mention is NMDAR activation. NMDAR are receptors on the cell. For these receptors to work properly, there are certain molecules that change or modulate these receptors that need to be present. Scientists have found that these modulators have been changed in ALS. This means NMDARs can’t work properly and result in possible cell death.
The main point of this article was to show that there are many factors that could play a role in the development of ALS and there’s plenty of research that still needs to be done. This leads me back to the Ice Bucket Challenge. By August, the challenge has raised over 100 million dollars. While this is amazing and shows the power that people have when they come together, the ALS Association’s spending has come into question. Is all this money going towards research? Sadly, no. Last year, they donated 28% of their funds to research. While some of the funds do go towards administrative and overhead costs, they also fund ALS public education and patient care services. I want to highlight that it is possible to donate to research only, and information can be found at their website. I hope that you have abetter understanding of ALS and what the Ice Bucket Challenge is doing.
Sources:
NMDA and ALS article
http://en.wikipedia.org/wiki/Amyotrophic_lateral_sclerosis
http://www.alsa.org/
 

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CTE to ALS, a Deadly Path

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ALS, the current neurological disease du jour, has been thrust into the minds of Americans via the now-infamous “Ice Bucket Challenge”. While the cause of this disease is not yet known, researchers have discovered many different players that may be involved. Neurotransmitter receptors, specifically AMPA and NMDA receptors are now being looked at for their participation in ALS. It is being hypothesized that an over-activation of these two receptors can lead to unnatural and damaging pathways in the neurons involved in motor activity. This explains the motor function lost in individuals with the debilitating disease.
Another hard-hitting neurological disease that only lately is beginning to be really talked about may be related to, or even a precursor of ALS. This condition is known as chronic traumatic encephalopathy, or CTE. CTE is a result of repeated damage to the brain, usually concussions, and involves changes in cognitive and behavioral functioning. Some researchers now believe that individuals with CTE are at a much higher risk to develop other neurological impairments, such as ALS.
Research of ALS and CTE are both in their infancy relative to many other human diseases. The little we do know about ALS shows that there is not one cause, but many different aspects of normal neurological functioning that can go wrong. While CTE does not always lead to ALS, and ALS is not only a result of CTE, there is a connection between the two ailments. The ALS “Ice Bucket Challenge” has brought much needed attention to the area of neurological diseases and what environmental aspects might lead to them. Does this mean that we have to pull every boy and girl out of all contact sports? I don’t believe a drastic reaction is necessary until further results are out, but parents need to seriously consider their children’s sports and what safety precautions should be carried out to ensure their long-term brain development and health.

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ALS: More Than Just the Ice Bucket Challenge

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In the last few months, the Ice Bucket Challenge has swept the nation with everyone from celebrities to your neighbor – and likely yourself too – completing this “challenge.” While the Ice Bucket Challenge has done an amazing job creating awareness and donations for this debilitating disease, few people truly understand what is happening for patients with ALS. Or why raising funds for research is so important.
ALS is a fatal neurodegenerative disease that stands for Amyotrophic Lateral Sclerosis – more commonly called Lou Gehrig’s disease. It involves the death of motor neurons in a person’s brain and spinal cord, which in turn causes muscle weakness, problems with speaking and breathing, and even paralysis. Because only the voluntary muscles are affected (like the muscles in your legs and arms), patients do not typically have problems with their heart or digestive system. But the inability to move and be “trapped in one’s body” can be devastating. Breathing, although usually involuntary, we can consciously control, meaning that it is also affected by ALS. Eventually, the patient requires a ventilator to breathe.
According to the ALS Association, every year in the United States 5,600 people are diagnosed with ALS, and at this very moment 30,000 people in the country suffer from the disease. After diagnosis, patients typically live for two to five years. Although ALS can be familial, this happens only 10% of the time. For the other 90%, onset of the disease is completely sporadic.
Currently, there is no cure for ALS and only one drug approved for treatment – riluzole – but it only extends the patient’s life by a few months. Why is it so difficult to develop treatments for this disease? The actual “cause” of ALS is unknown. It is believed to be caused by an overabundance of glutamate, an important neurotransmitter in the brain. This excess glutamate causes a particular receptor, called an NMDA receptor, to become hyperactive. When this NMDA receptor is active more than it should be, it results in too much calcium flowing into the nerve cells which eventually contributes to the death of the motor neuron. Until relatively recently, scientists believed that a different receptor, the AMPA receptor, was the main receptor involved with ALS. The brain and the many pathways of different neurotransmitters are very complicated, which only makes determining what is causing ALS more difficult. Mutations in a certain gene, called SOD1, could also have an effect on the development of ALS.
Why is this important? Because there are so many different pathways and possible reasons for the development of ALS in a person, it is essential that we conduct more research to help to discover and determine the best way to treat ALS. Ultimately, a cure for ALS could be found, but only with continual raising of awareness and donations. When the Ice Bucket Challenge craze has died down – as it eventually will – it is important that we do not forget about ALS. It is not a disease that gets a great deal of attention, but that does not mean it isn’t serious. It is a disease that progresses quickly and one that we need to remain aware of. Remember why you completed the Ice Bucket Challenge – not just for likes on Facebook, but to ultimately help the many people who struggle to walk, talk, and breathe as a result of ALS.

Disease/Health/Hot topics

ALS Challenge: I Nominate You to Dump Memantine on Your Head?

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Many of you have probably done the ALS ice bucket challenge and nominated your friends as a way to spread awareness for this disease.  Well I’m proud to inform you that it worked, people are paying attention!  So what exactly is ALS, what have we discovered about it, what in the world is memantine and why did I just nominate you to dump it on your head?  ALS is a rather nasty disease that causes the destruction of neurons within the spine and parts of the brain.  This destruction leads to muscle spasms and weakness that progresses to complete muscle paralysis and eventually death.  So what is causing the destruction of neurons?  It turns out too much glutamate within the nervous system is activating processes that create an influx of calcium into neurons causing the death of them.  So remove all the glutamate and problem solved right?  Wrong, we need glutamate for many aspects of regular neuron activity, so we need to find another method of controlling ALS.  That’s where memantine comes into play.  No I don’t want you to actually dump it on your head, it has a much more practical purpose.  Pharmacological treatments use memantine as a low-affinity, non-competative NMDAR antagonist to combat neuron degeneration in ALS studies.  That last sentence was a mouthful right?  It also may have left you more confused than when we started.  Well lets break  this sentence down a little.  NMDAR is a protein that is activated by glutamate and allows calcium to enter the neuron, which is the main issue occurring in ALS.  What this sentence is telling us is scientist have been using a drug named memantine to stop the activity of the protein NMDAR.  Memantine essentially plugs this protein like a cork and stops calcium from entering the neuron.  So it looks like we just cured ALS and can add one more point to scientific achievement!  Well as you may have guessed diseases of the brain are never that simple and we still have a ways to go.  We are moving in the right direction though and are making huge steps to understanding ALS and how to cure it.  So my challenge to you is to keep spreading awareness and nominate all your facebook friends to do the ALS ice bucket challenge. The attention this is creating for ALS is already producing results.

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Too Many Players on the Field

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ALS, or amyotrophic lateral sclerosis, is a disease that has received much attention in the past few months due to the infamous “Ice Bucket Challenge.” Though this blog is not a blog about said challenge, it is a blog about the debilitating disease- because, let’s be honest; you all probably know what the Ice Bucket Challenge is and maybe have even taken it, but do you know what ALS actually is? Until this past week, even I jumped on the popular social media bandwagon of the IBC but did not understand the complexities of the science and real-life impact of ALS.
ALS is marked by degeneration of motor neurons of the central nervous system. This means that as ALS progresses, it becomes harder and harder for the body’s muscles to be completely controlled. Thus some symptoms of ALS include muscle weakness, muscle atrophy (degeneration), and eventually paralysis. ALS is also fatal and progresses quickly to this end.
 

The above picture shows the path of a nerve from the brain to a muscle. The lower motor neurons are the ones affected by ALS.
This past week in Concordia’s Neurochemistry class, we read a paper discussing the science behind and players in the development of ALS in the body. Though ALS can be passed down in families, most of the disease happens by random chance. Contributing factors to the disease include: mutations in genes that cause some proteins to stop working correctly (particularly the SOD1 enzyme), too high of levels of glutamate (a key neurotransmitter in the body), improperly working cell-receptors that respond to glutamate, and many other failings of cellular systems in neurons. All of these factors lead to the ultimate death of the motor neurons.
The key message of the science of this article was that more factors then first thought contribute to ALS development. One thing going wrong doesn’t necessarily cause ALS, there are many players contributing to this field. The article focused on one specific receptor called an NMDA receptor that was previously not thought to be involved in ALS. This receptor may be more involved than scientists thought. All this goes to show that there may be more at play in complex disease than it seems at first, and one clear answer of what is going wrong may not be present.
ALS and its causes are complex. An eventual cure will probably be even more complex. Though awareness is a good thing, it will take much more than hashtagging and being cold for a few seconds to cure the complexities of ALS, but as scientists continue to research this disease, we can hope that they will find treatments that may eventually help ALS patients.
References:
The article I mention is from: http://www.sciencedirect.com/science/article/pii/S0925443912002736
The picture is from: http://web.alsa.org/site/PageServer?pagename=ALSA_Disease_Process_ALS

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ALS and the Chilling Reality of the Ice Bucket Challenge

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For many people they have recently been exposed to the acronym ALS through the very popular Ice Bucket Challenge, but how many of those people actually understand what ALS is and what they are contributing by participating. ALS stands for Amyotrophic Lateral Sclerosis and currently affects, according to the ALS Association, about 30,000 people have the disease at any given time in the United States. ALS is a neurodegenerative disease that affects many of the neurons in the brain and spinal cord, mainly those involved in movement called the “motor neurons”.  As the motor neurons begin to die off the victim loses control of their movement and the dying of these neurons eventually leads to their death. Recent literature has revealed that there could be some possible enzymes that have undergone a mutation that is leading to the symptoms and the diagnosis of ALS such as SOD1. However, there is no cure for this traumatic disease and very few medications have been established to help treat the disease. There is also no one test that can diagnosis ALS, so many patients do not know they have the disease until late into its unset.
Recently the Ice Bucket Challenge for ALS has been given much scrutiny due to many assumptions of only 7% of the money raised actually being given for research. However, the ALS Association dismisses this assumption and claim that by the end of the Fiscal Year 14 (FY14) that 28% of their funding was spent on researching treatments and a cure for ALS. In cases like this, it is most important that the community become informed with the cause and understand that things such as the Ice Bucket Challenge have a very critical purpose if completely understood. Awareness for diseases such as ALS is important, but ensuring the general public is also informed may be just as important to ensure that those participating in campaigns such as the Ice Bucket Challenge are respectful to those with the disease and to their family and friends.
However, beyond the scope of ALS many countries that do not have the clean supply of water that the United States is fortunate to have look at the Ice Bucket Challenge as a waste of clean water. So is this type of awareness the best approach to the disease or any disease at that? In the end do we know any one right way to address awareness of diseases such as ALS or is there even a right universal approach? Is the challenge anymore then a popular social media challenge? Do the members of the Ice Bucket Challenge understand what they are raising awareness for? These questions are not ones that can be simply answered yes or no, but need deeper thought and discussion to determine where the real cause of awareness can be found.
In the end is the Ice Bucket Challenge raising the right awareness or is it another social media trend and is it worth the money raised if the majority of those participating do not understand its true purpose?

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A-L-S: Can it E-N-D?

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ALS is a race. But not a normal race, not even close. This race does not have a definitive starting point, and you can be certain that the finish line is not clearly marked. Once it begins, (and I say “it begins” because it is not your choice whether you want to begin or not) you simply must continue the race until you are physically unable to keep moving forward.
Assuming we have not yet reached this physical end, we will continue as best we can until we can continue no more. ALS stands for amyotrophic lateral sclerosis, and if you polled the audience, I would bet money that not many would have any idea what “amyotrophic lateral sclerosis” actually was. Perhaps we poll the same audience and ask about Lou Gehrig’s disease─ a few more light bulbs come on, yet simply knowing the name is not the same as knowing the disease.
ALS is a neurodegenerative disease that tends to develop between the ages of 40 and 70 and is eventually fatal. Simply put, the motor nerves in your body that signal your muscles to move slowly break down until you no longer have the ability to coordinate your movements at all. Affecting roughly 30,000 Americans at any given time, ALS might not receive quite as much attention as Alzheimer’s or Parkinson’s, but these 30,000 people are still need our help.
There is currently no cure for ALS, and the only drug that is currently prescribed to treat it is called Riluzole which may extend a patient’s life only briefly, perhaps for a few months. Maybe a cure is still a ways off, but why haven’t researchers found anything that could help?
With each passing day, patients with ALS continue to fight for their strength. It is very difficult to know that your mind is intact, but you must deal with simple things like writing a letter or brushing your teeth becoming increasingly difficult. It may sound easy to just say ALS causes you to lose control over your muscles, but the human body is much more sophisticated. When the body is in working condition, it is extremely complex, and when things go wrong, they too are extremely complex. In class, we learned that researchers believe the main factor that causes the nerves to break down is overstimulation due to the presence of a molecule called glutamate.
Glutamate is important for all human─ whether in sickness or in health─ you need glutamate to survive. In the brain, glutamate is one of the key signaling molecules that is involved in many functions such as cognition, memory, and learning. Just like television, the signal itself is not useful without the proper receptors to receive and translate the signal. Back in the brain, there are two main receptors that receive glutamate as a signal. These are two protein complexes called AMPA and NMDA.
For many years, researchers believed that the AMPA receptors were the main culprit in causing ALS, but recent discoveries have shown that NMDA receptors seem to play a role as well. When glutamate binds to the NMDA receptor, pores in your cells are opened which allows calcium to flow between the nerve cells. These “calcium connections” between the nerves not only help to transmit your thoughts, but they are thought to be responsible for how memories develop.
In healthy individuals, these processes work as they are supposed to, but with ALS patients, these NMDA receptors become overactive, and this hyperactivity leads to the eventual death of the nerves.
As I said before, there is still much to learn about ALS, but by no means is it a lost cause. Many researchers are investigating the disease and are developing new treatments in the ultimate search for a cure. What I have listed here is just the tip of the iceberg; there is so much more to ALS that is worth caring about, just like the people that are currently coping with the disease. We are now nearing the end of our theoretical race, and even typing here to share this story is hard. The finish line is out there─ the end will come when we least expect it, and we will come to rest. There is no cure yet, but we will be patiently waiting. Eventually, ALS will come to an
 
Final thoughts on ALS written by Steven Dotzler

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ALS: Recent Publicity Reignites Awareness

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Scrubs episode “My Number One Doctor”

ALS awareness has taken the nation by storm recently thanks to the famous “ALS Ice-Bucket Challenge.”  I personally have little to no experience with ALS.  The only exposure I have had to ALS in my life has come in the form of my favorite tv show Scrubs.  One episode portrayed a patient (~30yrs old) who was struggling through the fast progression of her ailment.  This blew me away.  I hadn’t heard of this disease before and here it was trapping someone in a tomb of her own body.  What people don’t understand about ALS is truly how destructive it is and just how fast it can progress.  Many attribute the lack of awareness to this disease because it isn’t as “commercial” as cancer or Parkinson’s.
ALS essentially causes the degeneration of our motor neurons in our brain and spinal cord causing us to lose the ability to move.  This occurs because of a variety of reasons, causing motor neurons to go through the process of apoptosis (cellular suicide).  The pathway we covered stems from over-excitement of these motor neurons by the neurotransmitter glutamate, allowing too many calcium ions into the neurons.  Older research focused on the receptor protein known as AMPA because it was believed this receptor played the major role in triggering motor neuron death upon binding glutamate.  However, it is now being realized that another receptor known as the NMDA receptor plays a major role in triggering motor neuron death.  It is now known that the AMPA receptor helps to trigger the opening of the NMDA receptor which leads to an influx of calcium ions into the motor neuron which causes cellular changes, leading to apoptosis.  This is just another additional pathway which leads to the onset of ALS.
It is extremely difficult to find a solution to curing ALS because there are so many factors and pathways that cause the disease, many of which are just now beginning to be researched.  The average American citizen is not fluent in Neurochemistry or human physiology.  However, one thing we all are fluent in is compassion and speaking.  We have the ability to feel and try to understand peoples’ circumstances and thus communicate their situation in an effort to spread awareness and possibly help.
The ice-bucket challenge has been subject to large amounts of positive and negative responses.  Many people are unhappy with how donations are being utilized.  One thing those people are failing to recognize is simply important awareness is.  Research is able to take new routes thanks to new funding and this new  funding occurs thanks to new donors that are direct results of this awareness.  The ability of researchers to explore new routes towards understanding this disease bring us that much closer to a cure.  Hopefully by the end of our lifetime we can look at ALS as something other than a death sentence.
There is no cure for ALS at this point in time.  However, our healthcare system can provide more specialized care for those with ALS.  This specifically can occur in hospice care.  You see, ALS isn’t slow progressing and it’s a very unique kind of struggle that patients and their families are going through.  Specialized hospice care can provide better counseling for patients and families and at least make things as good as they can get until there is a cure.
In the meantime, consider this “would you rather” situation: Would you rather lose your motor function first (ALS), or your cognitive function (Alzheimer’s)?
Until next time…
-Sebastian

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Capping off Neurochem

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Honestly, I mainly took neurochemistry because I had to for my minor. I’ve never been all that into chemistry, and my expectations were about at the level of “this should be alright”. I thought it would be like a lot of other upper level classes: stuff I had learned before, but in a little more depth this time. We’d get a bit of new stuff after weeks of wading through dullness. I’m veeeery glad to say that I was wrong. This class ended up being exactly the way I like to learn, get some of the newest findings and wade in. It was great that rather than being dragged along a path that probably wasn’t much different from one a student year ago took, Dr. Mach was heading out with us into some unknown territory, if only a bit.
Each week we started on Monday with new journal article on some interesting part of neuroscience. We read it beforehand and came with some questions, then worked together, professor and students, to understand what the article was saying, what had been found, and what it might mean. Sometimes we got a bit lost, especially when we read that paper dealing with marijuana, or whenever Anchorman came up, but we always figured things out and got some questions answered. The questions we didn’t answer, including the new ones we’d come up with that day, became targets for Wednesday. We all threw out some topics we wanted to know more about, then decided who would take which one. Then for Wednesday we would research our topic in order to teach our classmates about it. For a while we ran with mini lectures, but after time kept running just a bit short, we changed to talking about our topics one on one with each other. On Friday we moved class to Knutson Campus Center (I think mainly for the couches), where we split into two groups, each with a couple discussion leaders, to spend the class just discussing the paper. We would help each other with lingering questions, talking about the implications or what we’d learned, both scientific and social, just occasionally, again, getting off topic… this was a pretty relaxed class. But we learned a ton, in a way that was far more engaging and enjoyable than most classes.
This was a capstone course, but I think for me personally it was a great way to cap off my time at Concordia. It was a good example of some of the best aspects of a liberal arts education here. We got through a lot of information, but in a small class where we could always ask questions or help steer the discussion. We helped each other learn more than we could have alone, or listening to some professor drone half a mile away at the head of a 200 person class, and we had fun while doing it. Experiences like this make me glad I chose Concordia.
 
 

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