Genetic Anticipation

The following article can be found in WorldHealth.Net 

Symptoms and signs of genetic conditions becoming more severe and/or appear at an earlier age as they are passed along from one generation to the next is known as the phenomenon called genetic anticipation

Genetic anticipation is a rather unusual type of genetic inheritance in which there is a progressive increase in mutation severity, that in some cases the mutation can result in a disease as it is passed along generation to generation from parents to offspring.

This unusual pattern of inheritance has been observed in a number of genetic diseases which includes neurodegenerative and neuromuscular disorders such as Myotonic dystrophy, Spinocerebellar ataxia type 1, Huntington’s disease, Dentatorubral-pallidoluysian atrophy, spinal and bulbar muscular atrophy, and Fragile X syndrome. Full mechanisms which are underlying genetic anticipation for the most part are largely unknown, but the phenomenon is associated with a type of mutation called trinucleotide repeat expansions, with other explanations suggested as being telomere shortening and nongenetic factors such as increased surveillance for symptoms and signs of a particular disorder.

Trinucleotide repeats are repetitive sequences of 3 nucleotides that follow patterns of CNG where in N can be any nucleotide, which can be found in the human genome within coding and noncoding DNA sequences. Unusual structural features of trinucleotide repeat sequences are thought to make them unstable and thus prone to errors during cell division. Trinucleotide repeat sequences are also thought to be able to form slipped-stranded DNA which is the misalignment of 2 complementary strands of DNA during replication, which allows the sequences to be looped-out and become trapped within hairpin structures. Hairpin structures are thought to stabilize slipped-stranded DNA strands which after further replication results in an increase in the number of repeat sequences if the hairpin formed in the lagging DNA strand, or a decrease in repeat sequences if the hairpin formed on the template DNA strand. Slipped-stranded DNA structures are transient and formation can occur during any genetic process which includes DNA separation into single strands which includes DNA recombination, replication, and repair.

Function and structure of protein that is translated from a region can be affected if repeat sequencing expansion occurs within coding sections of DNA, which can result in a loss or gain in function in the protein that can be harmful. How trinucleotide repeat sequence expansion in noncoding DNA is able to cause pathogenesis which can be observed in some disorders is not fully understood, possible explanations may be RNA degradation, chromatin silencing, and protein sequestration. Trinucleotide repeat sequence expansion is a progressive process that as the number increases the more likely it becomes that further replication errors while arise, and the number of repeats will expand further. This continuous expansion alters gene expression and will result in more severe phenotype as the mutation is passed along from each generation to the next. An example of this can be seen as expansion of trinucleotide sequence CAG in gene ITI5 will cause Huntington’s disease, with the age of onset correlating with the length of CAG repeat, and the greatest changes in the number of trinucleotide repeat sequences are seen with paternal transmission of the gene.

Buying a wheelchair is like buying a car

So many types and models, and so many options...how do I know what is best for me?

Quest Magazine has some great articles. A while back, there was one written by Kathy Wechsler called, “Front, Middle or Rear … Finding the Power Chair Drive System that’s Right for you.” For anyone in need of a wheelchair, new or replacement, this article is a good read.

Ms. Wechsler wrote that it is best to work with a certified rehabilitation technology supplier (CRTS) as well as an occupational or physical therapist who specializes in wheelchairs. They will perform an assessment and evaluate your particular needs and capabilities. She also recommends that you ask a lot of questions, and not quit asking until you feel comfortable with the answers you are getting.

My first wheelchair was a mid-wheel. It served its purpose, but the seat would not elevate. After about three years, I found myself having difficulty standing up from the chair. When I upgraded to a new chair, I spent several hours with a seating-specialist and occupational therapist. They evaluated my situation and my current capabilities. They asked dozens of questions regarding what my needs are today and what my capabilities might be five years out. Yes, five years.

Chairs are an expensive investment and you do not want to purchase one that will only fit your needs for the next 2-3 years. When I transitioned from a mid-wheel to a front-wheel drive with seat elevation, it was very different and I scarred a few door-frames in the first few weeks. I tend to like front-wheel more, but it took a little while to get used to it because of my experience with a mid-wheel.

Based upon information provided in the article and my personal experiences, I have listed some questions and considerations before purchasing a chair.

• Don't just consider today's needs. Since you want to have a chair that is comfortable and yet capable, always consider your lifestyle, capabilities and needs, now and five years into the future. Take your time and consider the right chair for the right reasons.

• How is your home configured? The size and setup of your home and office is very important in helping to make the right decision. Does the home have an open floor plan? How tight are the kitchen turns? Carpeting takes a beating with a wheelchair. Hardwood floors and tile are far more accepting. What are your home’s exterior and interior door widths? You want to be able to access your kitchen, living room, bedroom, bathroom, and closet. 

• What is the width and turning radius of the chair you are considering? Mid-wheel chair require a smaller turning radius. Are the chair’s arms adjustable? 

• How will you gain access to your home? There are portable ramps that are
  
  reasonably priced, or you can build a ramp. Portable ramps are nice when you visit other locations that are not handicap accessible. But, they are not light and easy to handle. Always consider a secondary exit plan in case of a fire or other emergency. Do you have a rear deck or porch that you want to access? 

• What type of seat and backrest do you need? Comfort is king. Since you will be spending several hours a day in your chair, a properly measured seat and backrest are important. There is nothing worse than having a seat or backrest that is uncomfortable or not quite right. An improper fit can also cause pressure ulcers (bed sores).

• How will you transport your chair? Do you have a wheelchair accessible vehicle?
  
  If so, will the new chair work with it? If you do not have a vehicle, what is needed to be able to take the chair with you? Wheelchair accessible vans are a fantastic tool. Fortunately, there are many used vans available today. There are also transport platforms that can be used on sedans or SUVs. 

• What type of suspension system do you need? Do you spend a lot of time outdoors? Usually front and rear-wheel drive units perform the best. There are also specialty chairs for the outdoorsman. 

• What kind of obstacles and inclines will you encounter during normal use? Front-wheel drive units perform the best for curbs, grass, gravel, snow and uneven terrain. Mid-wheel drive chairs can become hung up because they have front and rear casters. On the other hand, mid-wheel drive units are usually the most stable on inclines and declines. Normally, rear-wheel drive units are the least stable on inclines and declines, so it is important to have anti-tippers installed. 

• How fast do you need to go? For speeds up to 5 or 6 mph, all chairs perform well. For higher speeds, front and rear wheel drive chairs are more stable and easier to drive. 

• Do I need a Group 2 or Group 3 chair? Group what? There are seven groups of chairs. Most of us living with Kennedy's Disease will start out with a Group 2 chair and at some point might require a Group 3. Within these two groups, there are a variety of options (like accessories on a car). Some are not needed, but others might be helpful or even needed. 

• New or Used? There are a lot of good quality used chairs available. Most are a cost-efficient way to purchase your first chair when it is not medically needed yet. The key learning to take from a used chair consideration is the next point on who will service the chair. Do not assume your local dealer will service your chair if you buy it somewhere else. I learned this the hard way and it was no fun.

• Who will service your chair? Just like your car, this is very important. And, it is especially important if you purchase a used chair. I know of one man who lived two hours away from the nearest dealer. When his chair needed servicing, he could not find anyone who would make the trip. In-home-service is a wonderful convenience especially if the chair stops working for some reason.

• And, what will be your out-of-pocket costs - those not covered by your insurance provider? Most every provider has certain pre-purchase requirements. Know what they are ahead of time. With Medicare, for example, requires a Certificate of Medical Necessity (CMS) provided by your doctor. Also, they do not cover any of the cost for an elevated seat. They do not feel it is necessary. Those of us living with Kennedy's Disease might reach a point where the only way to transfer from a chair is with an elevated seat. 

To summarize—all three models of chairs have their pros and cons. That is why it is important to get a personal evaluation and assessment as well as to ask a lot of questions. I also advise asking an occupational therapist to tour your home. He/she will see things that you and I would not even consider.

If you have questions or additional comments based upon your experience, please let me know.

Progression is not always a bad word

Emerson said, 

"Life is a journey, not a destination." 

I write often about my life’s journey. In an earlier article, I used the analogy that the journey is like crossing a stream on stepping-stones. Each stone is a life experience that prepares us for the next one. Before we can fully step onto the next stone, we have to be willing to remove our foot from the previous one (our past beliefs, fears and anger).

It is possible to become so involved in the current stepping-stone (life experience) that it becomes nearly impossible to move forward. We have finally accepted “what is,” so we take a deep breath and say, “I can handle this.” Then, we cling to the moment refusing to let go. This usually happens for one of two reasons: fear or contentment. Today I will focus on fear.

Fear wears many masks. For example, something devastating happens in our lives and we just cannot move on. In fact, we would do anything to go back to the moment just before the crisis. It could be the loss of a loved one, a catastrophe, or a serious disease, or in my case Kennedy’s Disease. Whatever the reason, we find it difficult, if not impossible to move beyond it. Paralysis sets in and over time, wallowing in "what was" and "what if" and “why me” thoughts incapacitates any rational thinking.

I was living in the "contentment" mode for several years in my twenties. It took the realization that I had Kennedy's Disease to shake me to the foundation of my soul. It challenged most everything that I felt was sacred. The word entitlement perfectly describes my thoughts at the time.

My current journey over the last forty years is one filled with many challenges and even more unknowns. While going through something like this, acceptance does not come easy because it is difficult to look beyond the immediate fear, helplessness, confusion and pain.

Yet, once we can see beyond the moment, we tend to come out of these experiences stronger and more appreciative of what we have. We become more aware of the good that does surround our lives. We see and experience life a little differently because we are different. We are a survivor. And, with that realization, we take the next step and find life does go on.
  

Acceptance is a difficult pill to swallow. By breaking it into smaller pieces, however, it is easier to take. We learn from each experience. These small moments in time are like stepping-stones across a wide stream. Each one builds confidence and makes us more willing and less fearful to take another step.

Have I swallowed the entire pill and totally accepted my situation? Not even close. For I am continually being challenged. Nevertheless, I am progressing. Today, I am far more appreciative and understanding because life is still good and I know I can live with this disease. 

In addition, I found buried within this pill called "acceptance" something called "gratitude."

Image: https://steemit.com/selfgrowth

Something is Wrong!

It is sneaky. It creeps up on us during the prime of our lives. We initially deny its existence, but it just will not go away. We make excuses for a fall or the inability to do certain things, but something inside tells us “something is wrong.”

Then, when we finally admit we might have ‘it’, fears find a way of wedging their way into our daily thoughts. We feel isolated - alone and begin to imagine the worst. Because the disease is not well known, we have no idea what to expect. All we know is whatever is happening cannot be good.

As the disease progresses, we begin to pray for a miracle, or at least a treatment. We worry about our family’s future. We wonder if we will have to retire early. And, if we do, what does that mean for the family’s financial well-being?

Other little things begin to nag at us. Who will mow the lawn or do the home repairs? Can we afford to send our children to college? The concerns grow, and, they amplify as our strength fades. And, right about then, our manhood is challenged.

Our friends and family notice the change and want to help, but we shut them out. When that happens, all we have left is our hopes and prayers.

The reality is that the disease does progress. Fortunately, it progresses slowly. There are also brief periods of stability. These periods are something we look forward to because they give us time to adjust to our current capabilities. Unfortunately, we are never prepared for the next progression.

Whether the symptoms begin in our twenties or not until our sixties, the only thing we know is our strength and capabilities will decline.

This is “living with Kennedy’s Disease.”

Because the progression is slow, the actual disease is not nearly as bad as the emotional aspects of learning to live with the disease. Our fears are our worst enemy. Once we learn how to control the fears, we begin to adjust and start living again. When that happens, we see …

There is life after Kennedy’s Disease.

 

Getting a Good Night’s Rest

WikiPedia defines sleep apnea as a sleep disorder characterized by abnormal pauses in breathing or instances of abnormally low breathing, during sleep. Each pause in breathing, called an apnea, can last from a few seconds to minutes, and may occur 5 to 30 times or more an hour. 

A few years ago I hosted a chat room discussion on sleep apnea. My guest was Dave Hargett, Sleep Activist Coordinator for A.W.A.K.E. At the time, several men living with Kennedy’s Disease had mentioned that they had been diagnosed with sleep apnea. The question foremost in their minds was whether Kennedy’s Disease caused sleep apnea. The answer was, “No,” but he did say that sleep apnea is very prevalent in our society today.

Mr. Hargett recommended that anyone who felt they were having problems sleeping at night should check out their website at sleepapnea.org. He also cautioned that anyone concerned should contact a medical professional to receive diagnoses for any possible sleep related issues.

The concerns of those experiencing sleep disorders, and especially if it is sleep apnea, is the potential of experiencing memory problems, headaches, high blood pressure, weight gain, and increased risk of heart attack or stroke. Mr. Hargett also mentioned that it could affect your work.

There is also another issue. It concerns your spouse’s ability to get a good night’s sleep because you are snoring loudly and/or waking up periodically gasping for air.

A qualified medical professional can recommend a sleep-disorder specialist. If needed, the doctor will recommend a sleep study either in your home or in a controlled laboratory. If sleep apnea is confirmed, there are several potential treatments depending upon the severity of the issue. 

 
Changing body position: Many people have worse symptoms because they sleep on their back. By sleeping on your side, you might be able to reduce or eliminate your snoring.

Dental jaw advancement appliance: These are custom-made devices that are inserted in the person’s mouth at bedtime to open the airway by pulling the jaw forward.

Surgery: Children have their tonsils or adenoids removed and adults can have excess tissue removed (a result of aging). Unfortunately, surgery is not often very effective in treating sleep apnea.

CPAP: A “continuous positive airway pressure” device is the best treatment. The machine blows air at a set and regular interval into your airway. The device keeps your airway from closing. CPAP devices have not always been comfortable, but modern technology, including a nasal pillow, have helped make the adjustment easier.

Again, the key for those having difficulty sleeping, or the spouse is having difficulty sleeping because of your snoring, is to be properly diagnosed by a qualified professional.

Fortunately, I do not have sleep apnea, but I do have some problems sleeping. Because of some blockage in the nasal cavity and since I am a “back sleeper,” I use nasal strips every night . They make all the difference in the world to my sleep quality.

I know several men that use CPAP devices today. The have commented that the masks took some time getting used to, but they now swear by them. Do you have sleep apnea or have you used a CPAP device? If so, leave a comment so others can learn from your experiences.

Study identifies potential drug for treatment of debilitating inherited neurological disease

The following is an excerpt from a Medical Press article. To read the entire article follow this link: Potential Drug Treatment

March 15, 2018

Dr. Paul Taylor of St. Jude Children's Research Hospital ...

"... and his colleagues were led to seek drugs to treat SBMA because of findings from a previous study in his laboratory. The study pinpointed a molecular niche in the mutant androgen receptor protein that appeared to be a key to driving SBMA symptoms. However, that niche did not seem to be essential to the normal function of the androgen receptor. The study started with fruit flies genetically engineered to have the human androgen receptor, giving the scientists a living "test tube" to explore the effects of mutating the receptor.

"This identification of a small patch of this protein that appeared to be functionally important for driving the disease, but is not essential for most androgen receptor functions, gave us a potential drug target," Taylor said.

Pharmaceutical companies have been developing drugs to target this small patch, called the "activator function-2" or "AF2" domain. The companies were testing the drugs as possible treatments for prostate cancer, which also involves the androgen receptor. Taylor obtained a collection of the test drugs to evaluate for use with SBMA.

Using the genetically engineered flies, the researchers identified two drugs—whose long chemical names are abbreviated TA and MEPB—that alleviated SBMA symptoms. Then, using mice, the scientists determined that MEPB more effectively reached target tissues in the brain and spinal cord.

For their trials of TA and MEPB as potential SBMA treatments, the researchers developed a new genetically engineered mouse model to more accurately mimic the mutation found in men with SBMA. The transgenic mice showed many of the symptoms of humans with the disease.

Researchers found that MEPB effectively alleviated symptoms of SBMA in the mice. "Treating the mice with MEPB forestalled muscle atrophy and prevented loss of their motor neurons, with recovery of their testicles to normal size," Taylor said. "The treatment also protected their ability to walk and their muscle strength and endurance." ..."

The Roller Coaster Ride of SBMA

This last week two people have emailed me expressing their frustrations and anger with Kennedy's Disease. I can understand why they feel this way.  

Zig Ziglar said, “Getting knocked down in life is a given. Getting up and moving forward is a choice.” Feeling overwhelmed is something most of us with Kennedy's Disease have experienced. I have often said that the mental and emotional aspects of the Kennedy's Disease are as difficult as the physical ones. 

Today's post is a rambling of thoughts on the mental and emotional ride we go on after being diagnosed with Spinal Bulbar Muscular Atrophy.

Frustration is the anchor that keeps us from setting sail. What an interesting comment. Until we can let go of these feelings, we cannot truly live.

We have to ‘let go’ before we can move on. Trying to hold on to what we were, or currently have, is a losing proposition, especially with a progressive disorder. It is one that will always end in disappointment and frustration. Letting go of something we cherish, does not happen overnight. It could be the most difficult thing most of us will ever have to do.

Fear is False Evidence Appearing Real. Part of the difficulty of accepting our current condition is the fear of what tomorrow will bring. Fear of what might become is most often the reason we do not want to let go. We want to hold on to today and even wish for that miracle that will bring back normalcy (as we knew it). H. P. Lovecraft said, “The oldest and strongest emotion of mankind is fear, and the oldest and strongest kind of fear is fear of the unknown.”

Patience fosters acceptance and realism tempers expectations. I still get into trouble because I believe that I should be able to do something. If I would take the time to examine my current capabilities before beginning some task or project, I would be more accepting and comfortable with my current capabilities and expected results.

We judge what we do not understand. We tend to forget we are not the only people with problems. Thoreau said, "Could a greater miracle take place than for us to look through each other’s eye for an instant?" Be kind, for everyone you meet is fighting his/her own battle. It is easy to lash out when something does not go right. People do not wear signs explaining what is going on in their life. The person could have a heart condition, or just lost his/her job, or been in an auto accident that morning, or their child has cancer, or a spouse just passed away.

I will end today with another truism. Gautama Buddha said, "Resolve to be tender with the young, compassionate with the aged, sympathetic with the striving and tolerant with the weak and wrong. Sometime in your life, you will have been all of these."

Clip Art:  http://mariafresa.net/single/2069542.html

Let the light shine in

Happiness is a nine-letter word

Several people living with Kennedy’s Disease have mentioned bouts of depression. Many more, including myself, mentioned that anger and frustration was more prevalent in our lives since the onset of KD. I have discussed frustration several times in this blog. I do not have the cure (still working on that), but I found a good article on ways to feel happier and wanted to share some of the thoughts.

In the Yahoo Health article, "Six Natural Ways to Feel Happier," the author discussed some basic and easy ways to overcome the blues.

Sweat away the sadness – Research proves that exercise can improve mental health. I wrote about my experiences with endorphins a few times. The article said that working out can relieve mild to moderate depression as well as antidepressant medication because it stimulates dopamine in the brain (the feel good chemical). Even exercises like Yoga or stretching can help keep depression at bay.

Eat good food – Fish that contains Omega 3 fatty acids enhances areas of the brain that effect moods. Just by eating salmon, char, sardines or other fish (low-mercury swimmers) twice a week can make a big difference in your mood. Having a baked potato will also help (dose of vitamin B6). Also, foods rich in folate (e.g., spinach, beans and oranges) are filled with serotonin that will break through most blues.

Have sweet dreams – getting seven to eight hours of sleep each night is one of the best ways to beat the blues. People that have insomnia are five times more likely to experience depression. The article gives some helpful hints to help you go to sleep easier and stay asleep.

Claim some quiet time – Meditation is as good as most medications in reducing depression. From my personal experience, it does this and so much more. If you feel uncomfortable trying meditation, just try ten minutes of deep breathing each day. There are some deep breathing exercises in the Smart Exercise Guide.

See the light – Depressed people who experienced one hour of bright light each morning for five weeks experienced a 54 percent improvement in symptoms. Flick on an energy light to read the morning paper or spend some time in the early morning sun. Try sitting near a window where light streams in.

Phone a pal – It is not surprising that lonely people are more depressed. Strengthen bonds with at least three good friends. Set regular times where you meet at the park (or at the library or mall). Friends will make you feel better almost immediately.

I also recommend a hobby ... something that you enjoy and takes your mind off everything else.

Quote: Best-sunrise-quotes-on-pinterest

Still lots to learn

Living with Kennedy's Disease provides an opportunity for learning more about life and myself every day. 

I believe "nothing comes into existence uninvited." Everything that happens in my life is a potential learning experience depending upon how I respond to the situation. 

I further believe these erroneous beliefs and misconceptions I carry with me are tested repeatedly until I eventually understand and accept reality. If I react negatively to someone's actions, it is because I still have not fully accepted that everyone is fighting his or her own personal battle.

The quotes below are from Maya Angelou, a well-known and respected author and poet.

I've learned that…

• No matter what happens, or how bad it seems today, life does go on, and it will be better tomorrow. 

• You can tell a lot about a person by the way he/she handles these three things: a rainy day, lost luggage, and tangled Christmas tree lights. 

• Life sometimes gives you a second chance. 

• You should not go through life with a catcher's mitt on both hands. You need to be able to throw something back. 

• If you pursue happiness, it will elude you. But if you focus on your family, your friends, the needs of others, and doing the very best you can, happiness will find you. 

• Whenever I decide something with an open heart, I usually make the right decision. 

• Even when I have pains, I do not have to be one. 

• I still have a lot to learn. 

The "life goes on, and it will be a better tomorrow" comment above is similar to one of my favorite sayings, "This too will pass." My father use to remind me when I was a teenager, "it is not the end of the world," when I would over react to something negative in my life. Even though I did not want to hear it at the time, he was always right. 

In addition, the "decide something with an open heart" comment above goes hand-in-hand with Plato's quote that "everyone you meet is fighting a hard battle." Just recognizing that everyone is tested in his or her own unique way makes it easier to "accept the situation and move on."

Ms. Angelou has many wonderful quotes and sayings. One I particularly like is "a bird doesn't sing because it has an answer, it sings because it has a song." I hope you understand I am singing today even though I still do not have all the answers.

One thing is for certain, "I still have a lot to learn."

Not Everything is Predictable

Those of us living with Kennedy's Disease often like to compare symptoms, CAG Repeats, age of onset, and progression. I believe we do this to feel either better or perhaps worse about ourselves. Unfortunately, not everything is predictable about this gene defect. Allow me to give some examples.

Age of Onset: This could be anywhere from the teens to the 60s. Most often symptoms begin to appear in the 30s and 40s.

CAG Repeats: The number of repeats can be anywhere from the low 40s to the 60s. 34-39 is considered "borderline" and the person might only experience mild symptoms. Researchers now believe the higher the Repeats, the earlier the onset.

Progression and Severity: The earlier the onset, the greater the progression (more severe the condition). This is just a time factor. If onset begins in the 50s for one person and the 30s for another, the 30s person will have experienced 20 years of progression before the 50s person even experiences symptoms.

Symptoms: You would tend to believe that symptoms would be something you could count on, but that is not true either. There is a long list of potential symptoms, but not everyone has the same symptoms, nor do the symptoms appear at the same time in the progression of the disease. Go figure!

What else do we know about the disease?

Pneumonia: This is something that is not kind to us. Almost every doctor encourages us to have the pneumonia vaccination and the booster at age 65. They also recommend the Pneumococcal vaccine today. The flu is something we should also be concerned about because many times it can result in pneumonia. Once again, doctors encourage that you have an annual flu shot.

Exercise: Neurologists have not determined the true value of exercise for those of us with the defect. There is a consensus, however, that exercise if important to our wellbeing. The reason could be as simple as the benefits of endorphins and adrenaline to our general mental, emotional and physical health. Several doctors believe that it is important to continue to stimulate the motor neurons and muscles to keep them healthy as long as possible. And, “muscle memory” is very effective in helping to keep you mobile and upright. Everyone does agree that over-exercising does more harm than good. I can attest to that.

There is also the feeling that exercise and stretching helps "cell inhibition." Cell inhibition is what happens when an activity, such as an exercise, temporarily blocks an unpleasant sensation like a chronic pain. The nerve transmits the pain signal to a cell in the spinal cord that is inhibited by the new "traffic" caused by the stimulus (exercise routine). It is why pinching the cheek blocks the pain from the anesthesia needle in dentistry. Exercise and stretching (working the muscles and joints) produces stimuli for the spinal cord and brain (central nervous system), which is one reason we feel better when we move.

Sedentary Concerns: As the disease progresses, most of us with the defect become less active. We tend to spend more time sitting and do not work our metabolic system. For many of us, "couch potato" is a good phrase that exemplifies our lifestyle as the disease progresses. Weight gain and potential health complications because of the weight, as well as the additional strain on our existing weaker muscles, are always a concern.

Not Everything is KD Related: Just because we have Kennedy's Disease does not mean we are immune to other ailments and health issues. Diabetes, heart and lung disease, kidney failure, as well as many other health concerns are always a possibility as the body ages and based upon hereditary issues.

Continue seeing your regular doctor: Regular physicals and doctor's visits are important for your general health and wellbeing. One man, for example, complained for months about chest pains. He blamed them on Kennedy's Disease and felt he could not do anything about them. The pain finally became severe enough that he saw his doctor. Doctors diagnosed him with having blockage in his arteries.


Please feel free to comment. By taking a moment to share your thoughts you add much to these articles. The articles then become more than just something I said or believe. In addition, by adding a comment, you might just be helping the next reader by sharing your opinion, experience, or a helpful tip.

Impaired Protein Homeostasis in Neurodegenerative Diseases

Impaired Protein Homeostasis in Neurodegenerative Diseases

The below excerpt is from an article appearing in Select Science. Click on the title above to read the entire article. For a good explanation on autophagy, click on the link below the drawing to watch a video.

https://www.youtube.com/watch?v=PvnqzhtwGZU

“Learn how selective antibodies help decipher an impaired autophagy pathway in spino-bulbar muscular atrophy

Dr. Constanza Cortes, Assistant Professor in the Department of Neurology at Duke University School of Medicine, studies impaired protein homeostasis in polyglutamine diseases such as spino-bulbar muscular atrophy.

SS: What are polyglutamine diseases?

CC: Polyglutamine diseases are a family of inherited neurodegenerative disorders, all caused by expansion of a triplet-nucleotide, CAG, in the coding region of the affected genes. The most notable is Huntington’s Disease, caused by a CAG expansion in the huntingtin gene. Another polyglutamine disease is spino-bulbar muscular atrophy (SBMA), caused by a CAG expansion in the androgen receptor (AR) gene. As the CAG codon encodes for the amino acid glutamine, the resulting proteins all carry extended polyglutamine tracts, giving the name to this family of diseases.

I study SBMA, a neuromuscular condition that targets the skeletal muscle and motor neurons in the lower spinal cord. These express high levels of the mutant AR, that result in protein inclusions, accumulating in the nuclei of affected tissues. This suggests that impaired protein quality control may form the basis of the neurodegenerative phenotypes observed in SBMA.

SS: What is the focus of your research in spino-bulbar muscular atrophy (SBMA)?

CC: I focus on protein quality control mechanisms and investigate the role they may play in the pathogenesis of SBMA. Protein homeostasis (also known as proteostasis), is fundamental for the survival of neurons, and proteostasis dysfunction is a feature of many neurodegenerative diseases, including Alzheimer’s and Parkinson’s disease. Understanding the mechanisms underlying proteostasis dysfunction and uncovering novel targets for rescuing these defects may yield important therapeutic targets for diseases associated with proteostasis failure.

SS: How does impaired protein homeostasis contribute to neurodegeneration in SBMA?

CC: I have uncovered a previously unreported periphery-to-CNS signaling network originating in skeletal muscle. Using a transgenic mouse model for a gene that’s a master regulator of cellular clearance and metabolism, conditionally expressed in the skeletal muscle, I have shown improved proteostasis in the CNS during normal aging. This suggests that maintaining skeletal muscle proteostasis during aging may yield important neuroprotective benefits in the aging brain.

In agreement with this, these muscle-specific proteostasis-activated mice perform significantly better in neurocognitive testing at 18 months of age compared to their age-matched control littermates. This suggests the existence of secreted signals originating in skeletal muscle and targeting the CNS, resulting in improved proteostasis control in the brain. My current work focuses on identifying those signals and testing their ability to rescue neurodegenerative ‘proteinopathies’, including Alzheimer’s disease….” For more, click on the heading at the top of this page.

The Top 10 Benefits of Using a Wheelchair

Because of the slowly progressive nature of Kennedy's Disease, I fought using a wheelchair for several years. But, I must say, once I crossed over to the ‘riding’ side, I found there are some benefits. 

This is an update on a 2009 post and is meant to be informative and entertaining.

The Top 10 Benefits of Using a Wheelchair

10. You never become tired while shopping with your spouse. If she takes too long trying on clothes, you can recline the seat and take a nap.

9. You can go twenty-five miles at five-to-six miles per hour without breaking a sweat.

8. You have preferred parking spaces all over the city. (Most of the time anyway)

7. No matter how crowded, you have a special seating section at movies, concerts, and sporting events. It might not be the best seat in the house, but no one is sitting in front of you.

6. Many movie theaters provide discount tickets or have free admission for anyone in a wheelchair. Now this is a PERK.

5. Most people will step aside to allow you a better view (at the zoo, aquarium, parade, etc.).

4. If you bump into someone (accidentally or on purpose), they almost never take offense and often apologize to you.

3. You never complain that you have been on your feet all day.

2. If you have one-too-many, it is ‘almost’ impossible to stumble and fall. I will not mention last Thursday night.

1. If you insult a 300-pound ‘biker’, his reputation for being a tough-guy will not improve by stomping on you.

If you have a more reasons, please let me know.

Growing old with Kennedy's Disease

When initially diagnosed with ALS, I was devastated. I could live five years—perhaps ten if I was fortunate. When Dr. Fischbeck later correctly diagnosed me with SBMA, I felt I had a new lease on life. Then, the fears and paranoia showed up again. I was my own worst enemy. 

One thing I noticed while living with forty years of progression of Kennedy's Disease was that what negatively affected me (mentally and emotionally) in my late twenties and thirties is not a concern today. Most were unfounded fears of what could be, not what was. What I thought was earth shattering back then is something that I live with every day, and most often do not even consider today. In other words, I have matured with the disease and discovered more about it and about me.

In the beginning of my battle with this disease, I feared the worst and hoped for the best. I told little 'white lies' when asked if anything was the matter. Admitting I had the disease was something out of the question—especially at work. I looked at it as a weakness, something that will make me less of a husband, father, manager, and co-worker. Today, I realize that the real weakness was my inability to be honest with others and myself. Life would have been far simpler.

I now know living with the disease is never as bad as what I imagined. And, in some ways, it is worse. The most difficult part about living with the disease today is seeing how far my strength has deteriorated over forty years. The most satisfying part is knowing I am still active, engaged, enjoying life and helping others.

Today, "safety is job #1." When I am injured, I am not the only one that suffers. My wife has to change her life to accommodate my injury. That is why I error on the side of caution.

The Serenity Prayer, "God grant me the serenity to accept the things I cannot change (i.e., Kennedy’s Disease diagnosis), the courage to change the things I can (i.e., my bad habits, outlook,  attitude and patience), and the wisdom to know the difference." 

In closing, I leave you with my last and probably my most important learning. People are there for you when you need them.

Image: lawrenceofcyberia.blogs.com

Photo:  Trip Adviser                               

Problems with chewing and swallowing?

Benjamin Franklin wrote, “An ounce of prevention is worth a pound of cure.” Much of my life living with Kennedy’s Disease is focused on preventing or slowing the inevitable.

One area of the body that becomes particularly troublesome for those of us with Kennedy's Disease is often the most neglected. As the disease progresses, the face and throat muscles also weaken. Many of us begin to experience problems with swallowing, choking, dry-drowning (Laryngospasm), facial muscle wasting, jaw weakness, etc.

Some exercises will help maintain the throat, tongue and facial muscles and possibly delay or moderate several of the issues mentioned above. I practice many of these exercises several times a week (shown with an asterisk). They do help — especially with the chewing and choking issues. Try these exercises for a month and see if they help.

Stick Out Your Tongue: * Bite down lightly on your tongue to hold it in position. Swallow ten times (or more) while holding the tongue between the teeth. Perform this exercise every day. At first, you might find this exercise extremely difficult. Over time, it will become easier. [Strengthens throat muscles]

Large Smile:* Make the sound "EEEEEEEEEEEEEEEEEEEEEE" as you stretch your mouth muscles into a large smile. You should be able to feel throat muscles vibrate (stretch). Perform this routine ten times. [Strengthens throat and facial muscles]

Pucker your Lips:* Make the sound "OOOOOOOOOOOOOOOOOOO" as you pucker you lips. You should once again be able to feel your throat muscles vibrate (stretch). Perform this routine ten times. [Strengthens throat and facial muscles]

Stretch the Tongue: Open your mouth and stick out your tongue as far as possible. Be sure your tongue comes straight out of your mouth and does not go off the side. Hold, relax and repeat several times. Work toward sticking your tongue out farther each day, but still pointing straight ahead. Perform this routine ten times. [Strengthens tongue muscles]

Tongue Darts:* Stick your tongue out as far as you can and pull it back fast. Repeat ten times as quickly as you can. [Strengthens tongue muscles]

Circle the Mouth: Swab all your teeth and gums with your tongue. First, the inside of your teeth and then the outside. Perform this routine ten times. [Strengthens tongue muscles]

Vibrate the throat:* Say Mah-Mah-Mah-Mah as quickly as you can. Be sure there is an M and an AH each time. Then say Lah-Lah-Lah-Lah as quickly and accurately as you can. Perform this routine five times alternating between the sounds. [Strengthens throat muscles]

Hard Coughs:* Cough hard several times each day. [Strengthens the lungs and throat muscles]

Clear the Throat:* Clear the throat (um-hum) several times a day. [Strengthens throat muscles]

Big Yawn:* Take a deep breath and open the mouth wide as if you were yawning. With the mouth open wide, move the jaw from side to side. Perform this routine ten times. [Strengthens facial muscles]

Jaw Pushes:* Place the palm of your hand against the bottom of your jaw. While pressing up with your palm, open your jaw as far as possible. Relax the jaw. Perform this routine ten times. [Strengthens jaw muscles]

If you have other face, tongue, jaw and throat exercises that work for you, please let me know.