Congenital Insensitivity to Pain: The Mutation of the SCN9A Gene

Pain Free, Better Life? Not so much.

In a more recent module, some articles discussing individuals who do not feel any physical pain were read and reviewed on the piazza site. At first you think, "How awesome would that be, feeling absolutely no pain? I could do anything I want and not be affected by it at all!" However, according to scientists and doctors, the ability to feel pain is one of the most important signals our bodies give us when something isn't right. Pain signals our body when we are pushing it too far, it sets limits for us.

Ashlyn Blocker, a young girl from Georgia, suffers from a disorder called congenital insensitivity to pain. She can feel pressure, textures, and temperatures, but doesn't feel the pain that can be associated with these things. Ashlyn was diagnosed at a younger age when she was taken to the doctor because of a swollen eye. At first the doctors thought she just a had more severe case of pink eye, but when she didn't respond well to treatment, they sent her to an ophthalmologist who diagnosed her with a corneal abrasion, something that should be quite painful. After going to yet again another specialist, and going through numerous tests Ashlyn was diagnosed. Similarly, doctors in Northern Pakistan researched a family of six children who also suffered from the same diagnosis. They felt no pain, suffering from various cuts, bruises, broken bones, and more, these children were the amusement of others who were amazed by their lack of physical feeling. 

Ashlyn  Blocker

Both Ashlyn and the family of children who were studied all had a similar mutation. This mutation was found on the gene SCN9A. Nerves that sense pain are all along the body's surface and normally fire frequently when we touch something that is painful, like something hot or sharp. This sends electrical signals to our brains which then causes our bodies to react. These electrical signals are generated by molecular channels produced by the SCN9A gene. The mutation on the gene prevents it from making the channel, which then causes the electrical impulses to never be produced. 

According to Dr. C. Geoffrey Woods, a physician at Cambridge University who researched and worked with the Pakistani families, found that "the SCN9A gene is active in both nerves that mediate pain and in those of the sympathetic nervous system." However, none of these families suffered from any sympathetic nervous system disorders. This lack of side effects to the sympathetic nervous system is crucial to drug developers and researchers, and may help them target some kind of pain reliever. Dr. Woods also discusses how not all pain reception is controlled by one gene, and how it is surprising that a single gene mutation is responsible for a complete lack of feeling of physical pain. However, he found that the proteins made by the SCN9A gene cause the initial activity of the signal that is sent to the brain, and believes that because all pain fibers depend on this gene, when it is mutated, all those other fibers are altered as well.

Overall, this disorder is extremely rare and needs to be taken very seriously. A lot of cases of congenital insensitivity to pain end in premature death, with many serious injuries along the way. As I researched the topic more, I realized how thankful I am to be able to feel pain and know when my body needs a break or is getting pushed past its limits. Pain, in a way, is a gift that often goes unappreciated for all the things it does for us. Pain, although it hurts, is one of our body's best friends. 

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Molecular Cannibalism

Our digestive system is filled with enzymes that turn food into products our body can use. Components of our digestive system include the mouth, esophagus, stomach, small and large intestine, rectum and anus. Each plays a key role.
One helps break down proteins and carbohydrates. The pancreas secretes digestive enzymes into the small intestine while also producing insulin and glucagon. Insulin and glucagon are involved in maintaining levels of glucose, but that's another story.
What happens when the enzymes become active inside the pancreas and begin to consume the surrounding tissues and organs? Acute Pancreatitis; an act of molecular cannibalism. Acute Pancreatitis can be caused by gallstones or excessive alcohol consumption. Gallstones create a blockage of the bile and pancreatic ducts. The main symptom is pain in the upper left side or middle of the abdomen. It all begins with a protease, trypsin which is used to break down protein molecules in food. Inactive trypsin is stored into small organelles, zymogen granules. Yet, when Acute Pancreatitis occurs, they become free in the cytoplasm and begin to digest the pancreas. If the tissue has been destroyed and scarring develops, it can become Chronic Pancreatitis.
There has been no cure for this disease, but rather treatments such as pain medicines, I.V.'s antibiotics and changes in diet. One way to diagnose Acute Pancreatitis is by Therapeutic Endoscopic Retrograde Cholangiopancreatography (ERCP). It is used to view the pancreas, gallbladder, bile ducts and can be used to treat complications. Most treatments involve opening the bile ducts and removing the gallstones.
Scientists are working on prevention and treatment by looking at the processes the body goes through. Calcium ions are believed to play a major role in the premature activation of trypsin by causing the breakdown of the granules which resulted in the release of the enzymes. Yet, the rise in calcium ions is required for normal secretion, but can also cause this disease. Scientists believe short-lasting concentrations of calcium ions cause normal secretion while sustained high levels lead to the self-destruction.
Scientists have also discovered that the cells responsible for making these enzymes are protected from the effects of alcohol by preventing ethanol from causing the release of calcium ions. They also found that trypsin activation is dependent on calcium ions. The goal is to reduce the activity of the calcium ion pathways. One way is coffee. Coffee interferes with the channels and can also reduce the effects of excessive alcohol consumption.
This is only one case in which the body begins to attack itself. One that is more well-known is Celiac Disease. When an individual eats gluten, the immune system attacks the lining of the small intestine. This can be treatable with the help of a special diet. However, Acute Pancreatitis can create several issues and worsen if not treated properly or taken care of. One can reduce their risk of Acute Pancreatitis by limiting their alcohol consumption. With today's society, drinking is a social norm. However, it does take many drinks for Acute Pancreatitis to occur.
Someday, scientists will be able to develop successful treatments and further prevention will be on its way.
Our bodies are a very complex system, and can sometimes turn on itself.

Sources:
Pancreatitis
Acute Pancreatitis
Autoimmune Diseases
The War Within

Breathalyzer Used to Detect Lung Cancer

Lung Cancer is one of the world’s largest killers.  As of 2012, lung cancer has caused 1.56 million deaths on average per year.  Typically lung cancer is thought to be a direct result of cigarette smoke, but people who do not smoke can get this cancer as well due to genetic factors and being exposed to gases.  lung cancer is also called carcinoma of the lung.  It develops when cells in the lung begin to multiply rapidly and out of control.  The main difference between lung cancer and other types of cancer is the area of the body in which it occurs.  Previously detection of lung cancer was found using chest radiographs and computed tomography.  Since people are not usually tested for lung cancer until they start exhibiting symptoms, lung cancers are usually not discovered until it is too late for a cure.  However, researchers now think that they have found a new way to detect lung cancer, a breathalyzer. 

The University of Huddersfield researchers think that this breathalyzer will be able to identify lung cancer much earlier in its stages which would lead to a better chance to be cured.  They think that this breathalyzer will be able to distinguish people who have bronchitis or just a simple cough from the people that have lung cancer much more accurately.  Lung cancer symptoms have very similar symptoms to the common cold such as coughing, wheezing and shortness of breath leading to many people getting misdiagnosed.  If this breathalyzer can distinguish between cancer and a common cold then this would be a huge step for the cancer world.  A study conducted by Georgia Tech found 75 different compounds in the breath of people with lung cancer versus the people without.  Another study tested on people with breast cancer found that the device was able to detect people with breast cancer 78 percent of the time.

Each time a patient breathes into the breathalyzer chemicals from their breath are captured by the sensor in the breathalyzer.  The breathalyzer then breaks down the complex compounds of the chemicals to analyze the chemical makeup of the substance.  It is able to break down the complex compounds by using gas chromatography with mass spectrometry.  By looking at the different patterns in the chemicals the breathalyzer is able to see if they are similar to the chemicals in a cancer positive person versus a healthy person.  This new breathalyzer is much less expensive and much easier to test than the previous detection techniques.  When cancer is detected at its earliest stage, stage I, it is curable 70% of the time compared to the 25% of the time when it is usually detected in stage III.  These results are obviously not perfect and ready to be relied on, but it is definitely a huge step forward.  Before these tests can be utilized as the primary detection for cancer they need to be performed in larger studies to get a better understanding if this device is actually working versus the results just being a fluke.

My research sources are as follows:

Source 1

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Source 4

Have you ever seen an older person that has a noticeable tremor in their hand?

It is possible that that tremor you saw in their hand is actually Parkinson’s disease; this was the first sign that I saw when my grandma was first diagnosed with Parkinson’s disease. 

Parkinson’s disease is a disorder of the nervous system that worsens over time. Parkinson’s disease is the result of a lack of dopamine; where the dopamine-generating cells in the midbrain die. As a kid I did not know what the disease was, but I always heard my parents and other family members talking about it. As I got older I began to understand the severity of Parkinson’s disease and why my parents and family members had talked about it with such concern.  

      The cause of Parkinson’s disease is unknown, however majority of cases occur in patients after the age of 60. While the cause of Parkinson’s disease is unknown, it is believed that exposure to certain toxins, pesticides and other environmental factors can increase the risk of Parkinson’s disease. Other risk factors include gender and Heredity; Males are more likely than females to get Parkinson’s disease and even though Parkinson’s disease is not hereditary, having a close relative with Parkinson’s disease increases your chances of developing the disease. And since my grandma has Parkinson’s disease, my family and I have are supposed to have an annual checkup as a precaution to make sure that we are not developing Parkinson’s disease.

      It is hard to diagnose Parkinson’s disease because there are no lab tests that clearly identify the disease; therefore doctors rely on medical history, a neurological examination and ruling out other disorders that cause similar disorders. While there is no cure for Parkinson’s disease, there is only management to slow down the progression of the disease; options include medication, exercise, physical therapy, massage therapy and eating healthy. Preventive measures against Parkinson’s disease, in addition to avoiding toxins and pesticides, include caffeine consumption and tobacco use. Studies show that the higher the amount of caffeine that you consume the less likely you are to develop Parkinson’s disease. Tobacco use can reduce the risk of Parkinson’s disease by as much as 30%, as a result of the nicotine stimulating dopamine.

      Parkinson’s disease symptoms and signs vary from person to person however the common ones are: Tremors, Slowed Movement, Stiff Muscles which limit your range of motion, Impaired posture and balance, Loss of Automatic Movements such as blinking, Speech Changes such as slurring, and Writing Changes. Parkinson’s disease often times leads to Dementia or Alzheimer’s disease. Additional problems that usually accompany Parkinson’s disease include: Depression and other emotional changes such as anxiety, Problems Sleeping as well as other Sleep Disorders, Bladder problems, Constipation, Blood Pressure changes, Smell dysfunction, Fatigue and Sexual Dysfunction.  

      In my grandma’s case the doctors believed she developed the disease as a result of coming into contact with toxins in the factory she owned. And while Parkinson’s disease usually progresses relatively fast; however thanks to medicine to slow down the progression my grandma stayed relatively unaffected for around twelve years and then she started to develop more severe symptoms as well as other problems such as dementia. Research is continually underway to help us better understand Parkinson’s disease and hopefully in the near future they will develop a cure.

Sources:

Source 1 - Mayo Clinic

Source 2 - Wikipedia

Source 3 - Alzheimer's Association

Vegetarianism and Science

I’ve been a vegetarian for a while now, probably about four or five months, but only recently have I taken up running. During the school year, convo was always the place to go for me to eat good, healthy food, but over the summer I’ve felt as if I’ve had some difficulties in getting all of the nutrients I need, especially with my increase in physical activity. Just as a disclaimer before we go any further, I’m by no means a marathon runner, nor do I really run very far, but every day I try to go out after work (sitting behind the help desk at I.T.) and put a few miles behind me for health’s sake.

            During module 8, we discussed nutrition and the different diets humans have had over the years. One article in particular stood out to me: the one detailing the myths that have been circulating concerning the dietary change that allowed us to consume meat and its supposed relation to our cognitive development as a species. As a vegetarian I was very interested in this article, so I decided to do a little more research into what benefits might come from a vegetarian diet, especially for an athlete, even a casual one like myself.

            One of the very first sources that I went to when I first started running was Matt Frazier, writer of “No Meat Athlete,” a blog a lot like this one but with more targeted advice. I still think that it’s one of the best sources of help for vegetarians in general and for athletes in particular.  A great jumping off point for this blog would be his list of staple foods that vegetarians ought to be targeting for consumption. I won’t list off all of them right now, but I will provide the link to the site.

            Interestingly, one of the topics that we covered in class, the microbe communities in our guts, actually came up in my research. The article in question demonstrates that, though the different types of bacteria in the guts of the various subjects didn’t change drastically, their numbers certainly did, and thus the subjects were able to adapt to their new diets quickly and efficiently. Within four days, the subjects who had been instructed to consume strictly animal products had more bacteria that can withstand high levels of bile (bile is needed to digest meat) while the plant-only dieters’ genes involved in digesting carbohydrates increased their activity. The conclusion of the study poses the notion that “perhaps by adjusting diet, one can shape the microbiome in a way that can promote health.”

Finally, yet another article argues that vegetarians both help the environment and live longer. The conclusions of the study state that, even by reducing the amount of meat you eat without committing yourself wholly to a vegetarian diet you can enjoy increased longevity and reduce greenhouse gas emissions. What particularly struck me was the scope of the study; using Seventh-day Adventists in both the United States and Canada (a multi-ethnic and geographically diverse group) a “living sample” (as opposed to a simulated test) resulted in these findings. On an individual basis, it seems that if we want to help protect the environment and live longer, we might just want to start thinking about taking the plunge and switching to vegetarianism.

References:

http://www.nomeatathlete.com/vegetarian-diet-athletes/

http://news.sciencemag.org/biology/2013/12/extreme-diets-can-quickly-alter-gut-bacteria

http://www.sciencedaily.com/releases/2014/06/140625145536.htm

Progeria

Earlier in the class I did a post on Piazza on progeria, which in summary is the advanced aging of children.  Most children only live to be 12-16 years old before they pass away from heart problems that normally elderly people deal with.  Progeria is developed by the, “PRF-funded researchers identified FTIs as a potential drug treatment. The Progeria-causing mutation leads to the production of the protein progerin, which damages cell function. Part of progerin’s toxic effect on the body is caused by a molecule called a “farnesyl group,” which attaches to the progerin protein and helps it damage the body’s cells. FTIs act by blocking the attachment of the farnesyl group onto progerin, reducing the harm progerin causes.”(progeriaresearch.org). I want to look into some new research that has come available for treating progeria.  This article was posted in May of 2014 and it uses "Lonafarnib, a type of farnesyltransferase inhibitor (FTI) originally developed to treat cancer, has proven effective for Progeria" (progeriaresearch.org).  The scientists looked into how this drug affected the bone structure, hearing, weight, and blood vessel flexibility of blood vessels.  Each area showed improvement, but the most promising development was the increase in flexibility of blood vessels since that is the common cause of death for kids with progeria.  Though it was pointed out they do not know if this new discovery will delay the development of heart issues that come with the accelerated aging.  There was a 13abc news story a few weeks ago about the girl from Toledo who has progeria I mentioned in my Piazza post and she is receiving a new trial treatment.  I do not know if she is receiving the lonafarnib or not since they did not go into what the treatment specifically was.  Progeria also took national headlines within the last few years as 13abc out of Toledo has been doing great work with the girl in their area Barbara Walters did a special on several kids with progeria including the girl from Toledo.  This leads into the shear speed that progeria research has developed trials for these kids to try.

Children receiving their first treatment of new research medicine

The gene that causes progeria was found in 2003 only 11 years from our current year.  In 11 years they have had many promising trials that have yielded results in treatment of progeria with lonafarnib being the latest discovery.  The research developed in the search for a cure pf progeria has actually led a connection into the normal human aging process.  The progerin protein is produced more and more as we age and the development of the lonafarnib research could extend normal human life along with children with progeria.  If the research of the blood vessel flexibility improving continues we could see this maybe be a step in the right direction for the elderly and progeria patients.  Though this disease is very rare with only 200-250 children having progeria across the world the research associated could not only improve the life of children with progeria, but also make a cross into the normal aging process.  

This is part of the Barbara Walters interview of kids with progeria that was done within the last few years. 

http://www.progeriaresearch.org/first-ever-progeria-treatment.html