I Am Not A Victim

[This is another take on a 2009 post of mine]

One of my favorite saying is, "I choose my attitude in every situation." I choose not to consider myself a victim.

I will date myself by remembering the old Timex commercials where the watch would go through some ridiculous situation that no watch should survive and then John Cameron would say, "Timex—It takes a licking, but keeps on ticking."

A little while back, there was an article in the Goodlife Zen titled, "Why Some People Thrive No Matter What Happens.” The guest author, Gail Brenner, commented, “The key to remaining resilient is to not identify yourself as a victim.”

The dictionary defines "resilient" as “recovering readily from adversity; rebounds easily.”

Ms. Brenner commented in her article, "Resilient people understand that anything can happen. They realize that the world is not fair and that difficult things can happen to the most wonderful people. They figure out how to pick themselves up and move forward. It might take a long time and happen in tiny increments, but the predominant movement is forward—toward living and not just existing."

Another key comment in the article was, "Being resilient means understanding that we cannot control what happens to us, but that we can control how we relate to what happens. We get to choose. We can carry around the tragic events of our lives, letting them color the way we view ourselves and the world, or we can prosper." 

"…People who are resilient accept what happened, but resist defining themselves by it."

The author mentioned a study that revealed several qualities of resilient people. “Resilience People have:

• Strong relationships with people who support, encourage, and reassure 
• The willingness to allow strong feelings – anger, grief, fear – without avoiding them 
• Confidence – an attitude of "I can," rather than "I can't" 
• Trust in oneself and one's abilities 
• The capacity to learn from life experiences” 

“Resilient people nurture themselves, and seek help when needed."

Photo: https://elixirconsulting.com.au

Kennedy's Disease Videos

Some of us would rather watch a video than read a book or magazine. So, below are several YouTube videos concerning Kennedy’s Disease, KD research, personal stories of people living with KD, and a few other relevant topics. If you are aware of other videos concerning KD, please let me know and I will update this list.

Please note that some videos are not the best quality.

1. Dr.Fischbeck on Kennedy’s Disease
2. Spinaland bulbar muscular atrophy
3. Learningabout Kennedy’s Disease – Heather Montie, PhD
4. ChrisGrünseich - NIH Clinical Fellow
5. SBMA(KD) Clinic
6. KDModels – Part I - Lenore K. Beitel, Ph.D.
7. KDModels – Part II - Lenore K. Beitel, Ph.D.
8. Kennedy’sDisease – Part I – Ed Meyertholen
9. KD –Part II – Ed Meyertholen
10. KD –Part III – Ed Meyertholen
11. AfterTen Years – The KDA and KD Research – Ed Meyertholen
12. Sex& All That Jazz – Part I - Dr. Mary Ellen Romero
13. Sex& All That Jazz – Part II - Dr. Mary Ellen Romero
14. Kennedy’sDisease Free Children thru IVF
15. RevisitingKD Free Children
16. IGF-1/Aktsignaling in SBMA muscle - Maria Pennuto, PhD.
17. SmallHeat Shock proteins in SBMA - Angelo Poletti, Ph.D.
18. RareDisease Day and Kennedy’s Disease – (Personal Story)
19. Rare Disease Awareness and Kennedy’s Disease – (Personal Story)
20. Kennedy’sDisease – (Note 1^st three minutes are an introduction to KD)
21. A NewHandle on Kennedy’s Disease
22. Handtremor, tongue and perioral fasciculation in a patient with Kennedy disease
23. KD andthe Waites – (Personal Story)
24. UnderstandingMuscle Atrophy (Muscle Loss): Fitness Exercises
25. TreatmentDiary of Mr. Mattheis  - (Personal Story – Note information provided cannot be verified)

Lecture by Dr Fischbeck at Oxford University

This article was posted by Colin Hopps on the KD-UK blog. I think most everyone will find it interesting.

"Prior to this lecture at Oxford, my understanding of KD has been superficial but after reading an explanation by Dr Fischbeck and attending his lecture at Oxford University I have a much better grasp.


We have a repeat of a CAG pattern in the Androgen Receptor gene on our X chromosome. If one has up to 36 repeats you will not have KD but 38 and above you will and generally the more repeats the earlier the onset and severity. These extra repeats cause us to produce a longer Androgen Receptor protein which isn’t good but in itself would not cause KD, it is the toxicity it causes to the neurons and muscle cells this in turn damages the cells and ultimately results in the death of these cells. Below is the more technical description, took me several hours and Wikipedia to get a basic understanding.


So what is happening in the world of research regarding treatment? Well there are research groups in America, Copenhagen, Padua, Nagoya and here in London and Oxford. There is research mainly in five areas. ..."


Link to the entire post:  Oxford Lecture Notes

Why is my CPK so high - Revisited

Over the years, the post with the greatest activity has been “Why is my CPK so high?” Readers have posted more comments and asked more questions on this subject than any other post. For this reason, I thought it might be appropriate to review creatine kinase (CPK) and provide links to other posts on the topic.

The Johns Hopkins Arthritis Center provides a good explanation of creatinine kinase (CPK).

CPK also called creatine kinase (CK) is an enzyme (chemical) found specifically in muscle cells. One form of CPK is found in heart muscle cells, another in the skeletal muscle cells. CPK is also found in brain cells. When these cells are damaged for any reason, the CPK is released into the blood and can be measured by a blood test. If the heart CPK (CPK-MB) is elevated it can mean that the heart is damaged which can occur in a heart attack or in conditions in which the heart muscle is inflamed such as viral myocarditis. Skeletal muscle can be damaged in trauma such as in severe injury to the muscles, or after intense exercise causing an increase in the skeletal muscle form of CPK (CPK-MM). Certain drugs such as cholesterol lowering drugs (statins) can damage muscle and elevate CPK. Other causes are alcohol, viruses, hereditary conditions. Finally CPK can be elevated in certain autoimmune diseases that cause inflammation in the muscle such as polymyositis or dermatomyositis.

In the post on “Why is my CPK so high,” Terry Blytheway does a good job of explaining CPK.

“Going back to basics, there are three types of creatine kinase or isoenzymes in the body: CK-BB is mainly produced by the brain and the smooth muscle; CK-MB is primarily produced by the heart muscle; and most of CK-MM is produced by the skeletal muscle.”

He goes on to explain what higher than normal CPK might indicate.

“…if the test reveals that the level of creatine kinase circulating in the blood is higher than it should be in normal conditions, then chances are that the human body in question has suffered damage either to the muscle or the brain. In fact, astronomical levels of creatine kinase are indicative of injuries, rhabdodomyolysis, myocardial infarction, myocarditis, myositis, malignant hypethermia, McLeod syndrome, neuroleptic malignant syndrome, and hypothyroidism. If most of this sounds like gibberish to you, just remember that a heart attack, a muscle disease or a stroke may result in abnormally raised creatine kinase levels in the blood. Statin medications used to decrease serum cholesterol levels may also be the culprit.”

If you are interested, below are links to other posts on CPK.

• “Kennedy's Disease and elevated CPK”
• “Why is my CPK so high?”
• “Kennedy’s Disease and elevated CPK”

Mitochondrial Dysfunction in Kennedy’s Disease

I came across the following on the Kennedy’sDisease – Raising Awareness Facebook page:

I have been taking Acetyl L-Carnitine since September and have seen a dramatic improvement in the reduction of muscle fatigue, resulting in greater activity and better health overall. I started with L-Carnitine at 500 mg to see if there were any side effects, then after one month I switched to Acetyl L-Carnitine (which crosses the blood/brain barrier), again 500mg to start then 1000. Its hard to quantify what 'better' is in our lives, but.... so far this month, I have built 12' of cabinets in the dining room, built a 15x16ft glass greenhouse at the end of the drive and moved two pallets of brick pavers and two yards of soil. All jobs that have been waiting for several years.

There was also a link to the study and I have posted that below.

First, I must qualify myself. I am not a doctor or medical student. So, any comments are strictly of a layman with an interest. In reading the article, I noticed it was not a study. This article reported the findings in studying one patient with KD. It proposes the possibility of this regiment in helping improve energy (reducing muscle fatigue). The article proposes a more complete study to determine if the initial findings can be duplicated.

When there was a lot of excitement from other Facebook members wanting to give this a try, the gentleman responded with the following caution.

Please, everyone, little steps.... no one gains if you break your leg running to the store. Try a small dose in the morning with food if you like for a few days. It is expected to help with muscle fatigue only, so that means embarking on some activity as well. The aim is to feel better; not eliminate the disease. Too much too soon and you may experience side effects that remove it as a therapeutic tool.

This is sound advice. One patient doesn’t make a study. IMPORTANT: Always consult with your primary doctor and your neurologist before beginning any supplements, especially in high dosages.

Of course, anyone with SBMA wants to know more, so I looked up the definition:

Mitochondria: Structures located in the cell's cytoplasm outside the nucleus. Mitochondria are responsible for energy production. Each consists of two sets of membranes: a smooth, continuous outer coat and an inner membrane arranged in tubules or in folds that form plate-like double membranes (cristae). The mitochrondria are the principal energy source of the cell. They not only convert nutrients into energy but also perform many other specialized tasks. Each mitochondrion has a chromosome that is made of DNA but is otherwise quite different from the better-known chromosomes in the nucleus. The mitochondrial chromosome is much smaller than other chromosomes. It is round, whereas the chromosomes in the nucleus are shaped like rods. There are many copies of the mitochondrial chromosome in every cell, whereas there is normally only one set of chromosomes in the nucleus. All mitochondrial chromosomes are inherited from the mother.

Reference: NIH, US Library of Medicine, Genetics Home Reference. Mitochondrial DNA. 

 

I also looked up possible side effects for this supplement and this is what I found at WebMid.  

Acetyl-L-carnitine is LIKELY SAFE for most adults. It can cause some side effects including stomach upset, nausea, vomiting, and restlessness. It can cause a "fishy" odor of the urine, breath, and sweat.


Under-active thyroid (hypothyroidism): There is some concern that acetyl-L-carnitine might interfere with thyroid hormone. Don’t use acetyl-L-carnitine if you have an under-active thyroid.

Seizures: An increase in the number or seriousness of seizures has been reported in people with a history of seizures who have used L-carnitine by mouth or by IV (intravenously). Since L-carnitine is related to acetyl-L-carnitine, there is a concern that this might also occur with acetyl-L-carnitine. If you have ever had a seizure, don’t take acetyl-L-carnitine.

_________________________

Mitochondrial dysfunction in Kennedy’s disease: a new pharmacological target?

Chong Wang, Wei Chen, Dan Miao, Jin-Tai Yu, and Lan Tan

Abstract

Background

Mitochondrial impairment and elevated oxidative stress have been implicated in the pathogenesis of Kennedy’s disease. However, there is still no study describing the mitochondrial nutrient management in patients with Kennedy’s disease.

Methods
We assessed the clinical and electrophysiological features in a patient with Kennedy’s disease. This patient was diagnosed by genetic analysis. We also measured the plasma 8-hydroxydeoxyguanosine (8-OHdG) levels of the patient and his family members using commercial enzyme-linked immunosorbent assay (ELISA). Treatment with intravenous L-carnitine (2 g/day) for the patient was started on admission, followed by two weeks.
-

Goto this link to read the entire article

Image:  http://catalog.flatworldknowledge.com/bookhub/reader/2547?e=gob-ch20_s04

Kennedy’s Disease and ALS

Even though Kennedy’s Disease (SBMA) is becoming more widely known in the medical community, I still receive calls or emails requesting additional information on the condition after a person has been initially diagnosed with Amyotrophic Lateral Sclerosis (ALS). One major difference between the two conditions is that SBMA effects the lower motor neurons where ALS effects both the upper and lower motor neurons.

Sunday I received such a call. A woman in her late 70s was experiencing swallowing problems and the occasional fall. Her doctor diagnosed the health concern as Familial ALS (FALS). Since she never experienced any symptoms until the past year, she did her own research and came across Kennedy’s Disease. Several symptoms were similar to ALS and a few she felt fit her better. 

The average age of onset for ALS is in the mid-to-late 50s, however, there have been cases where symptoms first appeared in the patient’s 70s. The ALS Association has a good PDF report on the Epidemiology of ALS here.  To learn more about ALS, follow this link to the ALS Association.

I also ran across an interesting 2008 report on how Kennedy’s Disease mimics ALS. The summary is shown below with a link to the actual report. 

Kennedy Disease Mimics Amyotrophic Lateral Sclerosis:
A Case Report
Mu-Hui Fu, Min-Yu Lan, Jia-Shou Liu, Shung-Lon Lai, Shun-Sheng Chen,
and Yung-Yee Chang

Abstract- Kennedy disease (KD) is an X-linked inherited motor neuron disease that is often accompanied by androgen insensitivity. Its estimated incidence in the US is approximately 1 case in 40,000 men. KD has also been reported in individuals of different racial backgrounds, especially in Japanese but the prevalence rate in Taiwan has not been fully investigated. Here we report a case of KD definitely diagnosed by abnormal expansion of a polymorphic tandem cytosine-adenine-guanine (CAG) triplet repeat in the first exon of the androgen receptor gene. The direct genotyping from polymerase chain reaction product is subsequently performed utilizing capillary electrophoresis. The patient’s neurological conditions mimic amyotrophic lateral sclerosis (ALS). Since these two diseases have different etiologies and prognosis, it reminds us the necessity to rule out KD in face with a suspected male case of ALS.

Download the six page report here

ALS Image: ALS Association

KD Image: MDA

Who’s really in charge?

March’s CostCo Connection magazine had a nice article written by Wally Amos. For those of you who don’t know who Mr. Amos it, he is best known for his Famous Amos chocolate chip cookies.

The article, “Spring-clean your spirit,” reflects on his decision to give up trying to control his life. He writes about how he experienced many anxious moments that caused unrest and other challenges. When he began to analyze these experiences, he discovered that his attempt to control his life, and everything entering it, was causing him disruptions and failures in both his personal and business.

“Being in charge was so ingrained in my consciousness that I needed something more.” A message he remembered reading said, “For peace of mind, let go of being the general manager of the universe.” So, he decided to take a step back, get out of the way and remove himself from the picture. What he found was that there was constant love flowing into his life. He didn’t have to work for it or even search for it, because it was already there.

By changing his perspective of wanting (needing) to be in control, to one of accepting the love that already exists, he found a path of far less resistance.

He ends the article with the following question. “What beliefs are hidden deep within you that need changing? Identify them and clean them out. I promise you, life will become so much more productive, peaceful, fun and enjoyable. …Everything will be resolved when you put love first.”

Those of us living with a constant health issue, for example a progressive neuromuscular condition, often cling to past notions and beliefs. We want our health back. We want to be ‘normal’ again. We can’t understand why this happened. Why isn’t there a cure? Why me?

It is easy to become fixated on what was rather than what is. Acceptance is letting go of past beliefs. It doesn’t mean giving up. We are just giving up trying to control what we have no control over in our life. We will try to see the love and the good in our life without adding “but” or “if” or “should” or “shouldn’t.” We accept what is. We enjoy the rose’s beauty knowing that it also has thorns. And, with this acceptance comes peace and contentment.

I am not naïve enough to believe this change happens overnight. It takes work. There will be many failed attempts, but there will be some wins also. The thorns will still prick me, but I will not let them distract from the rose’s beauty. And that beauty is called “my life.”

Rose Photo:  2010_10300084 rs.jpgBy alive

Thorns Photo:  DSC_0132.JPG By kfjmiller

It’s Been 40 Years …

Who would’ve believed that when I woke up in the middle of the night forty years ago with a Charley Horse that cramp was just the beginning of the story. Those cramps were real buggers in those days. Sometimes they would last for 15-30 minutes. 

Back then, I just wrote them off because of my physical fitness program. I pushed myself in those days. I loved racquetball, tennis and running. I also worked out with weights three days a week. I viewed cramping as a part of the process of pushing myself, and the need for greater hydration. 

It wasn’t long after the cramping that I began to experience something that I called restless leg syndrome. My wife first noticed it and she brought it to my attention. The leg movement, like twitching, would last for hours. And, no matter what I tried, it didn’t help.   

Yet, for all of the strange happenings in my legs, I never felt better or healthier. In this case, ignorance can be bliss. I am so thankful I never went to a doctor because of the health issues. A doctor would have wanted to run some tests and perhaps prescribe medications. He/she probably would have advised me to back off in my fitness training to see if that helped. 

Ignorance was the best fit for me at the time. I am hot certain I could have handled knowing the truth and the ‘what ifs’ that go along with that knowledge. Perhaps knowing the truth would have changed my life when I was in the prime of my life. The reality of the actual condition, Kennedy’s Disease, along with the confirmation about fifteen years later, came soon enough. In the meantime, I lived a great life. Never once have I said, “I wish I would’ve known earlier.”

But, ignorance isn’t always blissful. What if a person has a treatable health condition or if diagnosing a condition early can improve the chances of curing it? The rules change!

That’s my story, however, and I’m sticking to it. 

Live your life the best way you can.

Image: ignorance-is-bliss

Kennedy's Disease Research; Future possibilities in

Last Saturday, Ed Meyertholen, the KDA's resident biology professor, was the KDA's Forum guest. As always, Ed provides information in a manner that is understandable to almost any audience.

Below are some of Ed Meyertholen’s comments and answers to specific questions concerning CRISPR and iRNA research. To read the entire forum discussion, follow this link: http://www.kennedysdisease.org/index.php/provide-support/chat-room-transcripts/2016-chat-room-transcripts/627-2016-february-06 .

“I am not a CRISPR expert, but the technique has been quickly (in the science view of quickly - several years) improving and it is expected that it will continue to do so. I do not think we will see this in humans for a while (years). 

In KD, I can imagine there may be issues on specificity - what cells to send CRISPR to, nerve cells or muscle (or both) and then one has to develop the procedures to specify the cells. The CRISPR work is very new and I do not know if anyone is working on it in Kennedy’s Disease. I suspect that someone will be soon. Nonetheless, I think that it has great possibilities - and I am usually not too optimistic. 

What happens is that they use a virus that normally attacks a specific cell type (like muscle), remove the DNA from the virus and replace it with the DNA needed to get CRISRP to work. The virus with the CRISPR DNA in injected into blood, goes to the muscle cells and instead of injecting viral (bad) DNA, injects the CRISPR DNA. The CRISPR DNA then lets the muscle cells make the CRISPR proteins which then should (and in the mouse, did) alter the DNA in those cells only. DNA in other than muscle cells is not affected. 

Kennedy’s Disease may give rise to other issues - the androgen receptor (the mutated protein) is made in many cells and may have effects (sexual issues, gynomatica (sp)), so we might want to alter the gene in other cells as well. It has great possibilities but it is not ready for prime time yet. This is the CRISPR paper:  http://www.ncbi.nlm.nih.gov/pubmed/26721684.

There was another paper from NIH (Kurt's lab) where they used iRNA to block the synthesis of the mutant androgen receptor and found that the mice got better. This is similar to work from LaSpada and from Lieberman that had been published a few years ago. These were done in conjunction with drug companies and I would not be surprised if there would be a clinical trial (I think that there is one starting using the same technique in Huntington's Disease) now. The other techniques with iRNA or ISO's are much closer to clinical use. If I remember correctly getting to nerve cells requires getting past the blood-brain barrier issue(s). Kurt's paper is here - http://www.ncbi.nlm.nih.gov/pubmed/26755334 .”

Photo:  http://www.science.ca/images/altman_rnase.jpg

Kennedy's Disease and elevated CPK

Serum creatine kinase, or CPK or CK, levels have been a warning sign of the possibility of many disorders including Kennedy's Disease, aka Spinal Bulbar Muscular Atrophy. Long before I knew I had Kennedy's Disease and before DNA testing was available, my doctor noticed the elevated CPK levels and wanted further testing done. Some of these tests were not a lot of fun. Fortunately, the DNA test is much easier, far less expensive, and more accurate.

As I mentioned in earlier articles, in the last few years my CPK (or CK) count has declined to the high end of the normal level. I can only guess why this has happened (less muscle mass = less wasting).

Yet, it is interesting that there is a strong correlation between elevated CPK and Kennedy;s Disease. While doing some research on the subject, I came across four recently updated articles on the link between Kennedy's Disease and CPK (CK).

1. The Better Health Channel updated their webpage on Kennedy's Disease, aka Spinal Bulbar Muscular Atrophy. The article is well written and easy to understand. It mentions elevated CPK as one of the symptoms, Click here to go to the link.

2. Disabled World also has information on elevated CPK and its potential link to Kennedy's Disease. The article is titled, Creatine Phosphokinase (CPK) Test: Facts & Information. Click here to go to the link.

3. Medscape's article on Kennedy's Disease has this to say about elevated CPK levels. "Problems may arise in resolving apparent positive results obtained before genetic testing is done. For instance, serum creatine kinase (CK) testing is not indicated, yet the CK level may be elevated substantially. One of the author's patients had been treated for inflammatory myopathy for years before the correct diagnosis was made. In another case, the patient was aggressively treated for myasthenia gravis (including thymectomy) before KD was diagnosed.^[63] Sorenson and Klein have also reported elevation in CK and transaminases levels in asymptomatic patients with KD^." Click here to go to the link.

4. Prezi has a short slideshow on Kennedy's Disease and also links elevated CPK levels as a possible symptom. Click here to go to the link.

CRISPR is in the news again

Last year I posted four articles on CRISPR. The technology is new and fascinating. There appears to be endless possibilities as to what it might be able to do someday. For those of us living with a neuromuscular condition (including Kennedy’s Disease), it offers hope. 

In this latest article written by Kate Lunau for McLean’s Magazine, researchers have taken another step forward in this quest for a treatment or cure.

Gene editing spurs hope for muscular dystrophy cure

For the first time, a breakthrough technique called CRISPR has been used to treat a genetic disease inside a living mammal

Kate Lunau  January 4, 2016 

“Of the many diseases that afflict us, those that strike young children seem especially cruel. One is Duchenne muscular dystrophy, which typically appears before a child’s sixth birthday. Sufferers (almost always boys) struggle with muscle weakness, and have trouble walking. By 12, most will be in a wheelchair; few live beyond their thirties. There’s no cure, and it affects about one in 3,500 males born worldwide. Suddenly, with the arrival of a powerful gene editing technique, new treatments seem to be on the horizon. In three independent papers, published in the journal Science, U.S. scientists snipped out defective DNA in mice with the disease—the first time this tool, called CRISPR, has been used to treat any genetic disease inside a living mammal—and restored some of their muscle function. ...”

Clickhere to read the entire article