Tuesday, March 30, 2010

The Slide

I have described those times where I wake up feeling substantially weaker. I call it 'the slide' because the day before it happens 'life is good' and everything seems to be going along just fine. Then I wake up and find it difficult to do almost anything. I never know how long I will be in the weaker state or if I will ever come out of it feeling stronger again.

I call the 'life is good' period 'the plateau'. It seems like my strength level has stabilized and I am more comfortable with my current capabilities.

'The slide' period is a difficult period for me both physically and emotionally. My muscles ache, my daily exercises are more difficult to perform, I just do not have the energy I normally have, just getting up and moving around is more difficult, and I can sense a new weakness that was not there before. As depicted in the picture above, the emotional aspect of 'the slide' is difficult. I do not know when I will reach the next plateau (when the slide will end) or where I will end up strength-wise. Fortunately, the plateaus last a lot longer than the slides. This break allows me to become comfortable with my new level of capabilities. Often, through focused exercise, I can come back a little.

As I become older, the slides seem to be less frequent, but more noticeable. When I was younger, the slides often occurred after over-doing it (I worked, exercised, or played too hard). Often after these events, I would have to rest for a day or more to recover. Since I am now substantially weaker, I believe the slides are more noticeable because of my current level of strength.

When I saw my neurologist last May and explained my most recent slide, he commented that he had never heard of something like this before. He questioned whether I was just having some emotional issues that were causing the physical symptoms. I convinced him that what I was experiencing was real and nothing to do with anxiety or depression. He then wanted to hear more about it. I promised to let him know the next time a slide occurs. He is a great doctor who listens and learns from my experiences.

This last Sunday was a good, normal day for me. Monday morning, I noticed that I was having difficulty with some of my exercises. Monday evening I was having difficulty standing up from my chair. This morning I was struggling to stand up and did not feel safe when standing for long. Is it the beginning of a slide? I hope not.

I would be interested to know if I am the only one that experiences these moments (then I would think it was psychosomatic) when you wake up weaker one day and struggle with the weakened state for several days.

Saturday, March 27, 2010

Role Reversal

The dictionary defines "role" as the actions and activities assigned to or expected of a person. "Reversal" is defined as the act of reversing the order or place of.

"Caregiver" is defined as a person who is responsible for attending to the needs of a child or dependent adult.

As my Kennedy's Disease progresses, I am becoming more accustomed to the role reversal that is taking place in our house. I originally fought it and often ended up injured because of my stubbornness (my wife has a mean right hook). Today, I am finding acceptance, rather than stubbornness, to be far less painful. It is still frustrating at times, however, because my wife's and my priorities are often different. Patience is the key, but I only have a limited supply of it.

Some examples of the reversals in our roles in life include:

  • Opening jars: My wife always came to me for help opening a jar. Now, I am the one looking for her help.
  • Feeding the birds: Since I am not very safe on uneven ground, my wife now has this responsibility.
  • Blankets on the bed: I use to need only a light blanket while my wife needed a blanket and a quilt/comforter. Today, I need an electric blanket plus another blanket across my feet while my wife just needs a light blanket.
  • Removing the leaves from the roof and cleaning the gutters: This was my job because I was not afraid of heights. Well, today I cannot climb a ladder and would not be safe on one even if I could.
  • Opening doors for the other person: I was raised to open the door for others. Today, my wife is the one opening the door for me.
  • General maintenance of the household, cars, and yard: If the repairs, replacements, or cleanup requires standing, climbing, lifting and holding, or repetitious movements, my wife now has the honor. And, she does not like to be supervised. J
  • Family protector: I was the one that considered alternatives in case of fire, threat, etc. Today, it takes me far too long just to get out of bed or up from a chair to be an effective leader in an emergency.
  • Helping hand in the neighborhood: I liked helping neighbors and friends. I enjoyed building and repair projects. My wife is the one that is usually volunteering to help today. I have been relegated to the role of water boy.
One big role that would have been a difficult reversal for me is that of "the breadwinner." Fortunately, because we planned for the worst-case scenario, my wife did not have to return to work after I had to retire early.

I do not envy anyone who has the role of caregiver. It is often a thankless and never-ending job. Fortunately, I have the most wonderful wife in the world. She is an excellent caregiver … unless I try to supervise her efforts.

Thursday, March 25, 2010

Frequently Asked Questions

I often receive emails that ask similar questions about living with Kennedy's Disease. In this post, I am generalizing these questions and providing the answers that I would normally give. Most questions have been answered at one time or another in this blog and that is why I am including the links to the article where I believe the question was addressed.

Q: My husband has tested positive for Kennedy's Disease, but he does not want to discuss it. How can I help if we cannot talk about it?

A: Acceptance is something that everyone has to go through at his or her own pace.  Many years ago, I wrote a short story about the typical nine stages of acceptance.  Last year I wrote a shortened version of the story for one of my blog articles (Nine Stages).  I also wrote specifically about denial in another blog post (Denial). 

Q: I heard there was a treatment for Kennedy's Disease. Is that true?

A: Reference a treatment for KD, at this time there is not one available.  We had a clinical trial a couple of years ago that was not effective.  That being said, there is some positive news on the research front. We are hoping for a new clinical trial with the next year on IGF-1 (Insulin-like Growth Factor - 1 for muscles).  The initial research performed was on pre-symptom mice. The results were quite encouraging.  The NIH is currently testing IGF-1 on mice models that already have Kennedy's Disease (KD) symptoms.  If this research also shows positive results, we should be able to move to a trial.  You can read more about it by clicking on these links (Mighty Mouse, IGF-1 News, and Chat with Maria).

In addition, another compound (ASC-J9) shows promise.  The NIH is currently running tests on mice for this one also.  If it is effective, we could see a trial within a couple of years.  You can read more about it by following this link (ASC-J9). Both of these researcher projects received grants from the KDA.

Q: If the muscles are wasting away, will exercise help or hurt me?

A: This is an interesting subject.  NIH hopes to have a clinical trial on the benefits of certain exercise within a year or two.  Currently, no one has researched the issue.  Most neurologists, however, believe that stimulating the muscles and motor neurons is an excellent way to help maintain them.  Last year after seeing a physical therapist, I published a Smart Exercise Guide for those of us living with KD.  The program is designed for those of us where the disease is more advanced, but can be modified for younger men also.  Regular stimulation of the muscles and motor neurons is the key in my opinion. 

Over-exercising, on the other hand, is far worse than not exercising at all.  Lifting heavy weights is not encouraged while using lighter-weights and aerobic exercises are encouraged.  To read more about exercise, click on these links (Exercise I and Exercise II).  A link to the PDF version of the exercise guide is in the second article.

Q: Are there certain foods I should or should not eat?

A: Diet is something else that has not been studied.  Neurologists, however, believe that a healthy diet is important.  Excess weight, especially as the disease progresses, becomes a serious burden on the weakened muscles and joints.  Diabetes is also a concern for several reasons including the fact that as Kennedy's Disease progresses, we become less active.  A serious side concern is that we often attribute many other health related issues to Kennedy's Disease and not see a doctor.  I wrote about it in this article (Other Health Issues).  The key is to moderate food and calorie intake to your current lifestyle.

In addition, as the disease progresses, swallowing and choking on certain foods and drinks can become an issue.  I wrote about this issue several times, but this article focuses on the problem (Three Keys).  

Q: I do not have several of the symptoms listed. Should I expect that these will show up later in life?

A: The progression of the disease is an interesting subject.  I wrote about the non-uniformity of the symptoms and progression in this article (Nothing Uniform).  Again, there is nothing uniform about the age of onset and progression of the disease.  Some experience certain symptoms while others do not.  Some progress at an accelerated pace, while others do not.  This is why I believe a person with KD should not be too concerned about what could happen (except for financial and family planning purposes).  Since we cannot predict the future, worrying about what we cannot do anything about is a worthless waste of time and energy.

Q: Where can I learn more about Kennedy's Disease?

A: The KDA website is an excellent reference for almost any subject on Kennedy's Disease.

If you have other questions, please do not hesitate to ask. If I do not know, I will try to find someone that can answer it.

Tuesday, March 23, 2010

Missing out because I am a minority

The Americans with Disability Act (ADA) has been good for those of us with limited mobility. At times, I feel it does not go far enough and perhaps too far at other times, but it is definitely a step (pardon the pun) in the right direction. It provides access for the disabled to most stores and buildings (as well as many other places).

Unfortunately, when we are not in the city, many places are still not accessible. In most rural communities, there are shops and stores that are converted homes. I do not expect the owners of these older places to rebuild entrances or open up inside areas to accommodate a small minority of shoppers/visitors. Yet, there are times that I do miss out on interesting rural shops and museums because the home or building is 100-150 years old (I also enjoy the
interesting architecture).

Our family, friends, and neighbors homes are mostly not accessible to me or offer limited access. Most of these homes have entranceways with several steps and no handrails. A few are even split-level homes offering no access at all. We have a six-foot ramp and a threshold ramp that does provide me access to homes with only a few steps. One neighbor even went so far as to borrow an eight-foot ramp to make certain I could come to his Christmas party. I miss visiting or having dinner at these non-accessible homes. I also regret that sometimes people stress out trying to figure a way for me to attend their function.

Most visits and dinners these days have to take place at our house. This works most of the time, but places a burden on my wife (the host's role). Family holidays are also difficult to plan. Only three of the six family-member homes are accessible. Two of Cindy's sisters have bent over backwards to accommodate me (or they just know my wife will not leave me home alone for a holiday). One built a ramp from their garage into the house. Another finished out a room in the basement (with lower level access) in order for me to attend dinners and functions there. One home with access to the main level does not have any restrooms on that floor making for interesting all day events. We manage to get by, but logistics plays an important role in the planning process.

Again, I do not expect the world to change because I cannot access someone's home. I am hoping, however, that someday stairs will no longer be such a barrier to me. Wouldn't that be wonderful?

Saturday, March 20, 2010

Another one of those moments

You know what I am talking about when I say, it was "one of those moments" that changed a relationship forever. Those of us living with Kennedy's Disease might have a few more than most people, but we all have them.

When I read the following story written by Stan Highe, another one of us living with the disease, I knew it had to be a "guest post" on my blog. It immediately struck home and made me flash on several pivotal moments in my life that a relationship changed because of the progression of the disease.

Arm-Wrestling for Food
Stan Highe - ©2010

I knew I had Kennedy's for some time, as did my family, but it didn't matter. I decided a long time ago that I would do what I could when I could while I still could, any way I could. This is just one of many stories, but sticks with me the most.

When you are parent with school-aged kids, there is always something to do after school. It might be dance, a play, sports, Scouts or any number of other activities. Often we would not get home until nine or ten o'clock. Even though it was late, and we were tired, we always seemed to be hungry, for anything.

This was one of those nights just like the others before. We just got home from a Scout meeting, and as always, the first stop was the refrigerator. It was a race between my son and I who would get there first to grab the choice "snack" or leftover. Wouldn't you know it, we both had our eye on the last piece of Apple pie, and so the contest began. To decide who would get it, we'd arm-wrestle for it. This was one of those moments of father-son bonding that I had to take advantage of while I can.

My son was only twelve and a little smaller than me, but already out-weighed me. That is really no surprise since I have only weighed about 125-130 all my life. (I am one of those people that have trouble keeping weight on) Still, I had the strength, or so I thought.

Like so many times before, my son and I lay down on the living room floor and assumed the position. Of course, my wife and daughter knew what was going to happen and were already laughing. My son had that same smile on his face he always got. He knew I'd eventually give in after a few minutes and let him have the tasty treat anyway. So, we started, hands and arms locked, but something felt different this time.

In past competitions, I would get his arm over where it would almost touch the floor, and then let up enough so he could win. This time as we lay there, I found I could not push his arm over past mid-point. I could keep him from moving my arm over, but that was it. It seemed like we were there for fifteen or twenty minutes; stalemated. Of course, he's giggling the whole time, unaware of what is really happening. Then I started to weaken. The pressure was causing my arm to move over more and more, but I could only hold against it. I couldn't push his arm back the other way. A few more minutes passed and my arm went over onto the floor.

We were done but instead of the usual smile, my son had a puzzled look on his face. Finally, he says, "You didn't let me win that time, Dad, did you?"

I smiled and said, "No, this time you really earned it." I don't know if he realized it- maybe he did and didn't let on- but I knew what it meant. I was getting weaker. As he went into the kitchen to claim his prize, I sat in my easy chair and rubbed my arm. We would have other moments as father and son in the coming years, but we never arm-wrestled for food again.


I hoped you enjoyed reading Stan's personal story as much as I did. His story again points out the emotional impact of the disease on relationships. Have you experienced one of those moments? Let me know if you have.

Thursday, March 18, 2010

Random Thoughts for Thursday, March 17, 2010

I have received a few emails asking whether I have my wheelchair yet and how I am doing with my writing. Today's post will address those two topics plus a couple of others.

What Happened to Spring?

About two weeks ago, our temperatures were in the sixties and seventies. I immediately noticed how good I felt again. My left thumb and index finger once again functioned correctly. Leg strength was substantially better and I had far less aches and pain. I tend to forget how winter temperatures take its toll on me until something like this happens.

Unfortunately, this week we are having a difficult time rising above the forties. My legs, feet and fingers are constantly cold. Everything I mentioned above has reverted to wintertime normalcy (but, who is complaining). Fortunately, more signs of spring are popping up and blooming. In addition, many of the critters that I follow on or around our property have begun the mating ritual. Perhaps spring is just around the corner.

I am Writing Again

Back in February, I wrote about my desire to start writing again. Well, I have been doing a lot of editing of older stories in my "Writer's Corner" to help me get back in the groove. I have also started outlining three potential stories.

  • The outline I am the furthest along with will be my third "Jason Seaborne" story. It is a murder mystery with international implications. Jason confronts an old nemesis from his boozing days.
  • I have another outline about my teenage years initially titled, "Who Would Be out Walking on a Night like This?" It is a true story about a double date where the four of us ended up "parking" on a country road. When a nasty thunderstorm pops up, we see someone walking towards us fighting the drenching rain and high winds.
  • Another outline I have initially titled, "Living and Dying at the Sam's Club," will be a satirical look at what life is like for a certain Sam's Club Shopper.
Still Waiting for my Chair

Well, it has been more than four months since my seating evaluation at Emory and I still do not have my chair. I just learned that all of the forms have been signed and submitted to my insurance providers for approval. Once approval is received, ATG can place the order. This process has been a real test of my patience. In the past, I was spoiled by having a neighbor as a friend and medical equipment provider. When I was forced to change providers, I lost that relationship and the entire process has moved forward at a snail's pace.

The length of this process reminds me of the joke about a snail knocking on the front door of a house. When the man opens the door, he sees a snail. "What do you want," the man growls. The snail replies, "I am starving, do you have any extra food?" The man, irritated that a snail has taken him away from the football game on TV, yells, "No!" and kicks the snail off the steps and into the street. A month later, there is a knock on the same door. When the man opens the door, the snail asks, "What did you do that for?"

Sunday's Guest Post

This Sunday I have a guest post from Stan Highe. He wrote a story about "one of those changing moments" in a family relationship. As soon as I read it, I knew it was right for my "Living with Kennedy's Disease" blog. It brought to mind some experiences that I had with my grandchildren as the disease progressed.

Tuesday, March 16, 2010

Is CP associated with KD?

I receive Google Alerts for any internet article related to Kennedy's Disease. Some of these alerts are interesting. I do not understand all of the research articles (Greek to me). The ones I do not understand I send these to a KDA board member who is a biology professor and ask him to explain it to me. There are always articles that have nothing to do with Kennedy's Disease except to reference it as a similar condition or similar symptoms. Then, occasionally, I receive an alert that really has me baffled.

In the last couple of months, several abstracts hit the alerts that relate to cognitive problems (CP) with those of us with Kennedy's Disease. When I read the transcript, I became frustrated because I find it hard to believe anyone can publish research results claiming certain cognitive issues in people with KD when only a small group of people (some related) were involved and the candidates were only monitored for a short period of time. One study referenced two patients studied in 1998. Another 2005 study speculates that perhaps cognitive issues (dementia) might also be present in people with Kennedy's Disease because of a single patient with KD that had these problems. It does not say there is a correlation, it just says that "perhaps" this is a problem and needs to be studied. A 2009 study of one man with KD states he complains of forgetfulness and has an altered social conduct. This study suggests that the disease may cause mild cognitive and behavioral changes as part of the disease's clinical manifestation.

Now, these studies have nothing to do with what my wife has to say about me ("You don't have a brain in your head!") when I do something stupid. She is normally right, but she is not referring to my cognitive ability. No, these studies are talking about real cognitive issues. Can you blame me for being a little defensive about this issue? We have enough problems without having to add "cognitive issues" to our list of symptoms. Besides, I do not want to give my wife any more ammunition.

I can say that I do not totally understand some of the findings in these studies (Greek to me). The "conclusions," however, are pretty clear. I did send one of the studies to the biology professor and he felt similarly to me that these were not realistic studies to draw any major conclusions from because of the small groups involved (perhaps he is also being defensive). He did joke that he could now tell people that he had a cognitive condition called Kennedy's Disease when he forgets something.

It just seems to me that dementia and other cognitive issues would be an issue with a small percentage of people with Kennedy's Disease, but nothing greater than the same issues with the general population. Why would we be any different? I know many people with Kennedy's Disease. Yes, as the disease progresses, most of us have a nasal voice and some facial distortion because of bulbar muscle issues. That, does not mean we have cognitive issues that are associated with Kennedy's Disease.

Am I being defensive? What do you think?

Saturday, March 13, 2010

Three Keys to Enjoying a Meal

Choking becomes more of a concern as the bulbar muscles weaken. Swallowing exercises have helped me greatly. I practice them every day, but still find myself occasionally having something lodge in my throat.

Sometimes, it is not choking, but clearing an object (e.g., crumb or skin) from the throat that causes problems. When this happens, the throat closes and I have difficulty breathing. Normally, if I do not panic and just relax while breathing normally, I can clear the throat.

Skins on apples, pears or tomatoes are often a problem for me. If I am very careful I can normally handle them, but it is easier if I do not try. Since I love apples and pears, my wife will often peel one for me and that helps. Bread or cracker crumbs are always a problem if I try to breathe while it is in my mouth. Occasionally, I will have a problem with tortilla chips. Stringy vegetables are also a problem if I am not careful. If I chew them thoroughly I can normally get by okay.

The key for me is to:
  • chew food thoroughly before swallowing,
  • take smaller bites, and
  • not talk while chewing.
Unfortunately, I forget one or more of these keys quite often.

Personal Example: We were out to dinner with friends about a month ago. I broke one of the rules (talking while chewing). As I began to talk while still chewing on a chip, a crumb stuck in the throat. I felt the throat close and I gasped for air. The strangest sound comes out when this happens. Our friends were about ready to leap across the table and administer a "Heimlich" on me, but my wife just looked me in the eye and said, "Relax, try to breathe normally; you'll be okay in a moment." (She is always so calm when I am suffocating to death) I could see the eyes of our friends questioning whether they should help, but because my wife was calm, they just sat there (as I turned blue). Within a minute or so, I was okay again except for the red face and sweaty forehead.

Relaxing seems to be the key if I begin to choke. Unfortunately, it is not easy to overcome the fear associated with not getting your breath, and tightening up only makes matters worse. I have learned that if I take slow breaths I can still cough hard (especially if I practice the routine regularly). It is always good to have a coach nearby to help talk you through the process (or just in case, you really need them to clear your passageway).

As a reminder, I am including in today's post the Heimlich process.

Instructions: (Courtesy of eHow)
Step 1: Ask the choking person to stand if he or she is sitting.
      Step 2: Place yourself slightly behind the standing victim.

      Step 3: Reassure the victim that you know the Heimlich maneuver and are going to help.

      Step 4: Place your arms around the victim's waist.

     Step 5: Make a fist with one hand and place your thumb toward the victim, just above his or her belly button.


     Step 6: Grab your fist with your other hand.


     Step 7: Deliver five upward squeeze-thrusts into the abdomen.


     Step 8: Make each squeeze-thrust strong enough to dislodge a foreign body.

     Step 9: Understand that your thrusts make the diaphragm move air out of the victim's lungs, creating a kind of artificial cough.

     Step 10: Keep a firm grip on the victim, since he or she can lose consciousness and fall if the Heimlich maneuver is not effective.

     Step 11: Repeat the Heimlich maneuver until the foreign body is expelled.

  Also, in case you are alone:


Thursday, March 11, 2010

IGF-1 Does Look Promising – Part II

In Tuesday’s article, I discussed the research that Dr. Maria Pennuto and others are doing using IGF-1.  Today’s article is a small portion of the transcript of that chat with some additional explanations and definitions provided by me.  For those of us not very scientifically inclined, some of the explanations might be over our head.  Do not let that stop you, however, because there is the potential of a major breakthrough for our children and possibly for those just beginning to show the symptoms of Kennedy’s Disease.

Q:  Could you bring us up to date on your IGF-1 research?
DRMP:  IGF-1 is a factor that promotes cell survival.  IGF-1 works by initiating a signal that modifies factors that are inside the cell. 
IGF-1 is outside the cells, but binds a factor on the cell’s surface.  After this event, a series of changes end up with activation of a factor named AKT.

Q:  What does AKT stand for and mean?
DRMP:  AKT is what we call kinase.  It is an enzyme that adds a phosphate group to specific sites in the protein.  [Kinases are used extensively to transmit signals and control complex processes in cells] The Androgen Receptor (AR) is a target modified by AKT.  So, IGF-1 activates AKT which in turn modifies the AR.

Q:  How does this modification influence SBMA (Kennedy’s Disease)?
DRMP:  We have shown that once modified by AKT, the AR is no longer able to bind testosterone.  This finding was surprising and very important for the disease because the disease is triggered by testosterone.  We have also shown that the AR modified by AKT gets degraded by the cell … it does not accumulate in the cell.  So, we decided to use this information to see if in the mouse model that IGF-AKT-AR signal could be used to attenuate (weaken, reduce severity) the disease. 

Q:  What is the difference between IGF-1 and IGF-1 for muscles?
DRMP:  That is a critical point.  In a cell, there are several types of IGF.  Some act systemically and are generated by the liver.  Muscle IGF is the form of IGF-1 used in our previous study.  We know that in principle the muscle-generated IGF works in the mouse model, but to use this approach in humans we need delivery via a virus.  Dr. Fischbeck at NIH is using IPLEX, which is another form of IGF already used in humans.  If this works, it is to our advantage. 

Q:  What is IPLEX?
DRMP:  IPLEX is binary protein complex of human insulin-like growth factor-1 (rhIGF-1) and human insulin-like growth factor-binding protein-3 (rhIGFBP-3), both produced by recombinant DNA technology which means that is acting systemically.  [From Wikipedia:  Mecasermin rinfabate (trade name IPLEX) is a drug consisting of recombinant Insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3).  It is a drug already approved for use by the FDA.]

Q:  In your research, when IGF-1 is started pre-symptom, the mouse had a later onset of Kennedy’s Disease and less severe progression of the disease.  Correct?
DRMP:  Yes, in our experiments, if IGF was there before disease onset our mouse models were producing more IGF afterwards.  It remains to be established if this can work in the mouse models being tested after disease onset.

Q:  You commented earlier that your original research was on pre-symptom Kennedy's Disease mice.  How about those of us that already have the symptoms? 
DRMP:  Yes, Dr. Fischbeck is now testing IGF-1 (IPLEX) on mice models already showing symptoms (just after disease onset) because patients are already symptomatic when diagnosed with Kennedy’s Disease.  Dr. Fischbeck wants to see if IGF-1 will slow the progression after the disease’s onset. 

Q:  And, what if IPLEX does not work?
DRMP:  We are also generating viruses expressing IGF-1 (muscle-generated) just in case IPLEX does not work.  Of course, these viruses have to be tested in mouse models first.  We have already discovered a huge effect of IGF on skeletal muscles in SBMA mice compared to the control group of mice.  What is also important is that intervention in muscle preserved motor neurons in the spinal cord, suggesting that if we can protect muscle we can also do something for the neurons and it can be easier to plan intervention for muscles than for the spinal cord.

Again, this is just a short portion of the chat.  You can find the entire transcription at the KDA web site under Chat Transcripts.  Look for the March 06, 2010 chat transcript.

This is pretty exciting stuff.  Other research projects are also making headway in finding that elusive treatment for Kennedy’s Disease.  I find it encouraging that several of these projects are focusing on finding ways to allow the androgen receptor to do its job.  I do not know about you, but chemical castration just does not appeal to me (ouch!).

[Author's Note:  On March 13, I updated several sections above after conferring with Dr. Pennuto]

Tuesday, March 9, 2010

IGF-1 Does Look Promising

This last Saturday the KDA chat room's guest was Dr. Maria Pennuto from the Department of Neuroscience at the Italian Institute of Technology in Genova, Italy. Maria is also a 2009 recipient of a KDA research grant. Her current work with insulin-like growth factor 1 (IGF-1) looks very promising for a treatment of Kennedy's Disease.  This research is based upon results that Maria discovered when she worked at NIH.  She found that a specific modification of the mutant androgen receptors results in decreased toxicity.  This modification was due to the activation of an enzyme known as AKT. I felt her work is important enough to include a portion of Maria's chat in today and Thursday's articles. Please understand that since I am not a doctor or researcher, whenever I give an explanation it is only my interpretation of the information provided and I might not explain everything correctly.

"IGF-1 for muscles" shows a great deal of promise in mouse models. The original study was on mice that had the defective gene, but were not showing symptoms yet. In these mice, the IGF-1 reduced the amount of androgen receptor present in the cells and therefore delayed the onset of Kennedy's Disease and slowed the progression once symptoms began to show up. The current study at the National Institute of Health (NIH) is using mouse models that have shown symptoms. Researchers are trying to determine if IGF-1 still works, works to a lesser degree, or does not work at all once Kennedy's Disease symptoms are present. This current research will also help determine the viability of IGF-1 in humans.

A little background information might be useful here. Cells from a person with Kennedy's Disease have a problem cleaning the residual caused by testosterone within the androgen receptor (AR). The cell's nucleus actually rejects the AR when it tries to enter it for cleaning. Because of this, the AR cannot free itself from the residuals (garbage) that are clinging (binding) to it. Eventually, the AR becomes so clogged that it can no longer function and dies.

To give you a more common example to explain what is taking place, it is like having an engine with a clogged oil filter. The oil becomes so gummed up over time that it can no longer do its job and the engine eventually malfunctions and dies. IGF-1 appears to allow the androgen receptor to clean the garbage caused by testosterone buildup thereby keeping it healthy and able to do its job. Using the same oil filter example, if you keep the oil filter clean so it can do its job, the engine will run better and last a long time.

Something else came out in the chat that was interesting. Many of us with Kennedy's Disease have wondered which came first, the chicken or the egg (e.g., how did Kennedy's Disease actually start especially in a family lineage)? According to Maria, the CAG part of our DNA is somewhat fragile and almost any abnormality can change the number of repeats. In other words, a family with no history of Kennedy's Disease could all of a sudden have one or more children with the defective gene. I had always assumed that somewhere in a family's history was a carrier.

The KDA has a saying when it comes to supporting research.

"Working together to find a treatment or cure
… for our generation, and for our children and grandchildren."

Even though it looks like IGF-1 will not be viable for us "more elderly" gentlemen (aka old codgers), it does look promising for those not showing any symptoms and possibly those who are in the early stages of Kennedy's Disease. As a parent, I believe that would be a tremendous step in the right direction in minimizing the impact of Kennedy's Disease on future families.

Meanwhile, we patiently wait the results of future testing and hope for a clinical trial. For someone that is not known for having a lot of patience, these waiting periods seem like an eternity.

Sunday, March 7, 2010

The easiest way is not always the best way

When the physical therapist first came to my house to begin my exercise program, he asked me to perform several basic functions for him. I knew he was assessing my strength, but I did not know he was also looking for bad habits. As I went through my routines of sitting down, standing up, walking, etc., the therapist just stood there without commenting. When I was through he explained what he was seeing in my current practices and why I was often doing more harm than good.

One routine that I began several of years ago was how I stood up from a chair. I compensated for the weakness in my quads by spreading my legs as far apart as possible, leaning over my legs, and pushing up while trying to get my weight (torso) over the knees. He said that this was a mistake. He asked me to keep my legs vertical (directly underneath the knees) and not spread them. He also wanted me to use my arms more to push off as my quads took control of lifting the torso. He felt that the spread-leg position was actually more dangerous and put too much stress on the quads. He was right.

Another routine (nice word for bad habit) of mine is how I walked with a cane or walker. I placed a lot of weight on my arms (or arm if using a cane) to hold me up while walking. This forced me to lean slightly forward. The P.T. asked me to trust my legs a little more and use my arms only if I needed them. The therapist said that I was using my arms as the main means of support and this was causing posture problems as well as tiring me out quicker.

He also said to stop looking down while walking. I needed to stand upright and look forward to change my posture and center of gravity. One way he helped me accomplish this shift was to raise the height of the cane and walker so that my arms were at a 45-degree angle to the cane's handle and walker's grab bars. I did not feel comfortable with the change initially, but the more I practiced the easier it became.

While standing over the kitchen and bathroom counters, he noticed that I also leaned forward. He said I was doing the same thing as when I was walking. The center of gravity and posture were in front of me and not in alignment. Week after week he had me standing at attention (shoulders back and eyes facing forward) to keep the spinal column straight and aligned. He also had me perform an exercise every day where I stand with my feet slightly apart and back straight (standing at attention). I then began to rock to the left and right (shifting my weight to each leg) sixty times as I maintained a straight (aligned) posture. I gradually gained confidence, strength, and improved my balance. This is now one of my morning exercises.

The key for me was how I felt during the routine and afterwards. I did feel safer (more in control) and stronger. My balance also improved with my increased leg strength. I also found it easier to breathe when sitting or standing with the body aligned (straight).

That is the good news. The bad news is that I am still a little lazy. It is easy to revert to my bad habits on those days I feel weak. Fortunately, the daily exercises and practice makes it easier to catch myself and correct these bad habits.


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. You can comment by clicking on "comments" below or by sending me an email. I look forward to hearing from you.

Thursday, March 4, 2010

There is Nothing Uniform About This Defective Gene

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, there is nothing 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. A person is considered "borderline" with repeats from 34-39 and might only experience mild symptoms. Researchers are still trying to determine if there is any correlation between the number of repeats and the age of onset, severity, or progression. Recently, a few have commented that the number of repeats does reflect upon the severity of the condition.
  • 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.
  • Progression and Severity: You cannot count on this either. Some of us experience difficulty walking in the 40s and 50s while others are still working (including performing manual labor) or even skiing in the 60s. Go figure!
What do we know about the disease that is important to everyone with the defect?

  • 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. 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 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. 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 and why rubbing a child's wasp bite helps the pain. 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.
    • Everyone tends to agree that over-exercising does more harm than good. I can attest to that.
  • 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 as we should. 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.
  • Blame Game: 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.

    • It is very important that we not attribute all symptoms and health concerns to Kennedy's Disease. 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. He was diagnosed with having blockage in his arteries.
    • Just because there is no treatment for Kennedy's Disease does not mean we should discontinue seeing our doctor. Regular physicals and doctor's visits are important for your general health and wellbeing.


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. You can comment by clicking on "comments" below or by sending me an email. I look forward to hearing from you.



Tuesday, March 2, 2010

Random Thoughts for Tuesday, March 02

We are being snowed in again. We already have three inches on the ground and it is supposed to snow for several more hours. This is the fourth or fifth time this year we have not been able to get off the hill. In our seven years living here, this is the first year we have had this problem (snowed-in or iced-in). "But, who is complaining … not me!" I did get Fred, my Beagle, out early this morning when it was sleeting. We will not be going for any more walks today. Our driveway and the hill are just too steep and ice over easily. Since we live in the country, we have to wait for the melt because our county does not maintain these roads.

This past week I have been spending a lot of time moving my short stories to Blogger. The link to my new site is The Writer's Corner. The reason for the move is laziness. WordPress uses different coding than Blogger. Since I have my Living with KD blog on Blogger, I found it a little frustrating to move between services (trying to remember two applications and different coding versus one). I still have several more stories to post, but I am happy with the results. I have added more pictures and cleaned up a little of the writing. In the process, I also transferred 123 comments. That was the hardest part of the project, but I felt it was important to keep everyone's thoughts.

I just sent out an announcement about the new KDA polo shirts. The response so far has been excellent. This week I also plan to send out the Kennedy's Disease Association (KDA) Annual Report. I finished writing it this weekend and I believe it tells a good story (accomplishments and 2010 goals).

Well, we are doing are taxes this morning, so I will sign off for now.


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. You can comment by clicking on "comments" below or by sending me an email. I look forward to hearing from you.

Monday, March 1, 2010

Insulin-like Growth Factor 1 (IGF-1) Might Reduce AR Toxicity

I copied this article from the Science Codex web page.  Many of us living with Kennedy's Disease are very interested in this recent research using IGF-1 and hope that a clinical trial might be available within the next year.

Maria Pennuto will be our guest researcher on the KDA chat room this Saturday, March 6, at 10:30 AM Eastern Time.  This chat will give you an opportunity to hear the latest updates on Dr. Pennuto's research as well as to learn about other Kennedy's Disease research projects.  

Mighty mice: treatment targeted to muscle improves Kennedy's Disease

New research with transgenic mice reveals that a therapy directed at the muscle significantly improves disease symptoms of a genetic disorder characterized by destruction of the neurons that control movement. The study, published by Cell Press in the August 13th issue of the journal Neuron, highlights a promising new treatment for this currently incurable and nontreatable neurodegenerative disorder.

Spinal and bulbar muscular atrophy (SBMA), or Kennedy's disease, is a neurodegenerative disease that attacks the neurons that control muscle movement. The disease, which only fully affects males, is characterized by substantial weakness and wasting in the muscles that have lost innervation. Previous research has shown that a specific mutation in the gene for the androgen receptor (AR) causes the disease. The mutation causes the accumulation of a mutant protein that damages the motor neurons.

Recent evidence has suggested that the mutant AR may also exert a direct toxic effect on the muscle. "Although the extent to which SBMA pathogenesis is a consequence of neuron degeneration and secondary muscle atrophy, or primary damage to the muscle, is not known, these observations suggest that skeletal muscle may be an important target for disease treatment," offers senior study author, Dr. Maria Pennuto from the Department of Neuroscience at the Italian Institute of Technology in Genova.

Dr. Pennuto and colleagues had previously shown that phosphorylation of AR by Akt blocked the activation of the AR, and that insulin-like growth factor 1 (IGF-1), which activates Akt, is a protective factor for muscle and reduced mutant AR toxicity in cells grown in the lab. "These observations suggest IGF-1 and Akt-mediated inactivation of AR as a potential therapy for SBMA," says Dr. Pennuto. In the current study, the researchers extended these findings and demonstrated that IGF-1 reduces AR activation in cultured cells through phosphorylation of AR by Akt.

The group also generated SBMA mice that expressed high levels of IGF-1 in skeletal muscle. Notably, the IGF-1 used in this experimental paradigm is a form of IGF-1 that is specifically produced by muscle. The mice exhibited increased Akt activation and AR phosphorylation, specifically in the muscle, and this correlated with reduced accumulation of the disease protein in the tissue.

Importantly, augmentation of IGF-1/Akt signaling also improved motor performance, body weight, and muscle and spinal cord pathology, and extended survival in the SBMA mice. "Our study establishes IGF-1/Akt-mediated inactivation of mutant AR as a strategy to counteract disease in living animals and is the first to demonstrate that skeletal muscle is a viable target tissue for therapeutic intervention in SBMA," concludes Dr. Pennuto.

Source: Cell Press