Monday, November 28, 2016

Did you miss the KDA Conference and Educational Symposium?

I did too. I understand there was 104 attendees.

Six of the clinical presentations are posted on the KDA website. I know, it isn't the same as being there and having the presenter explain each slide and answer questions, but it is better than nothing.

Personally, I found the one on Pain and Kennedy's Disease to be enlightening. And, Dr, Jordan's presentation on what causes all these crazy things to happen is challenging a lot of what we were told. I am hoping it leads to breakthroughs.

You might also want to check out Paul Lazenby's Facebook comment on the SFN Conference that Paul attended after the KDA Conference.

Friday, November 25, 2016

SBMA Study published regarding the AR113Q Muscle

This research paper was published a month ago.

Rescue of metabolic alterations in AR113Q skeletal muscle by peripheral androgen receptor gene silencing

Elisa GiorgettiZhigang YuJason P. ChuaRyosuke ShimamuraLili ZhaoFan ZhuSriram VennetiMaria PennutoYuanfang GuanGene Hung, and Andrew P. Lieberman1,


•Decreased expression of carbohydrate metabolic genes characterizes AR113Q muscle
•AR113Q skeletal muscle shows decreased glycolysis and altered mitochondria
•Peripheral gene silencing by ASO rescues expression of muscle energy metabolism genes
•Altered muscle energy utilization contributes to non-neuronal disease manifestations


Spinal and bulbar muscular atrophy (SBMA), a progressive degenerative disorder, is caused by a CAG/glutamine expansion in the androgen receptor (polyQ AR). Recent studies demonstrate that skeletal muscle is an important site of toxicity that contributes to the SBMA phenotype. Here, we sought to identify critical pathways altered in muscle that underlie disease manifestations in AR113Q mice. This led to the unanticipated identification of gene expression changes affecting regulators of carbohydrate metabolism, similar to those triggered by denervation. AR113Q muscle exhibits diminished glycolysis, altered mitochondria, and an impaired response to exercise. Strikingly, the expression of genes regulating muscle energy metabolism is rescued following peripheral polyQ AR gene silencing by antisense oligonucleotides (ASO), a therapeutic strategy that alleviates disease. Our data establish the occurrence of a metabolic imbalance in SBMA muscle triggered by peripheral expression of the polyQ AR and indicate that alterations in energy utilization contribute to non-neuronal disease manifestations.

Wednesday, November 23, 2016

I love Thanksgiving

Thanksgiving is an important time of year for me. It is a time when our family gets together to 'break bread' and share our thoughts. Once everyone sits down, and we all hold hands to pray, sighs can be heard around the table. At that moment, everything is all right.

It is easy to focus on the negative things, but Thanksgiving gives us an opportunity to say THANK YOU for all the good–for all the blessings in our lives.

Today, I am thankful for …
  • The men and women of our armed forces, and their families. They sacrifice so much without adequate appreciation, compensation or reward.
  • For the fire, rescue and police men and women who are there for us in time of need.
  • Being able to live in this country. We often complain about what is wrong, but we seldom say thank you for all that is right. I would not want to live anywhere else.
  • The doctors and researchers who are searching for a treatment or cure. I have said it before, but without them there would be no hope.
  • My wonderful, thoughtful, patient, understanding and beautiful wife. She makes life worth living every day.
  • Both of our families, as well as our friends and neighbors. These people are my support system. Life without family and friends would be pretty miserable and boring.
  • My overall health and the health of our families. Too often we take this for granted until something bad happens.

From our house to yours, have a safe, 
healthy and happy Thanksgiving

Photos from, wikipedia,and wikimedia 

Monday, November 21, 2016

As a kid, I loved slides

… but they sure aren’t any fun these days. Thr rapid progression (loss of strength) is rather scary.

Early last week my legs started giving indications of a slide. For the next four days strength and capabilities diminished. By Saturday I was not a ‘happy camper’. I should know better because I have been through more than a few of these battles over the last 40 years, but I still think the worst for a day or two.

Saturday afternoon I had enough of the wallowing in frustration and took an accounting of what might have got me here. Even though I exercise several times every day, over the last few weeks I often spent four-to-six hours just sitting. I realized this was not my normal routine.
So, sitting on the throne that afternoon, I decided to change my modus operandi. Every two-to-three hours I was going to stand up and perform a couple of short exercises. Three times that day seemed to make a difference the next morning. Six times yesterday felt even better. I could tell I was on my way back.

I’m not 100% back, but today I feel 90+% back to normal.  

I believe Henry Ford said, “If you always do what you’ve always done, you’ll always get what you’ve always got.” This also holds true in my personal life. If I don’t like the results, I need to do something different.    

Photo: Giant Bomb

Wednesday, November 16, 2016

Kennedy’s Disease BVS857 Trial

Many of us have been patiently awaiting the published report on the recently concluded Kennedy’s Disease BVS857 trial at NIH. Two of the attendees provided the following information on the trial. Once the actual paper is published, I’ll provide a link to it

Dr. Kenneth Fischbeck of the NIH gave a report on this trial at the KDA Conference in San Diego last week. He stated that while there were some modest positive results it did not meet expectations. In part that may have been because they only conducted the trial for 12 weeks and the nature of the drug and its effect would suggest slowly increasing benefits over an extended time frame.

The compound was intended to improve insulin sensitivity in people with KD and boost the anabolic effects of insulin and IGF1. Unfortunately, it also stimulated an immune response in some patients taking it producing anti-bodies that not only attacked the drug but also attacked the person's own insulin or IGF1. Fortunately for those affected after discontinuing the drug the immune response faded. Novartis aborted their trial plans and terminated further investigation of the compound.

The following is a quote from Dr. Fischbeck. “We too are disappointed that the Novartis agent was not more effective, but we are optimistic that the results from this trial will help in developing a treatment that really works for Kennedy’s disease. The study gave us information about muscle imaging and clinical outcome measures that will improve the design of future trials, and it helped to set up a network of trial sites that will allow clinical studies to be done more efficiently. Also, it gave an indication in the effect on muscle size that other drugs targeting the same pathway might be effective.”

Friday, November 11, 2016

Our Greatest National Debt

I am recycling a post from 2011. Let's never forget what these men and women, as well as their families, sacrificed to serve our country.


In this morning’s paper was a well written commentary by Fang. A. Wong titled, “For those who served.” Mr. Wong brought forward the case that even though our national debt was a very serious issue, the biggest national debt is that which America owes to its veterans. He proposes that November 11, Veterans Day, is the “perfect opportunity for us to take a historical audit on just how much this nation owes to her heroes.

The author commented, “Our debt to these heroes can never be repaid, but our gratitude and respect must last forever.” Mr. Wong said that less than 10% of Americans are veterans. “... American warriors do not complain. They endure. Warriors make do with less. Warriors finish the job, no matter how hard, no matter what is asked.”

He asks us to remind our lawmakers that there is a debt we all owe to those who served. The author concludes his article with a statement from George Washington. “The willingness with which our young people are likely to serve in any war, no matter how justified, shall be directly proportional as to how they perceive the veterans of earlier wars were treated and appreciated by their country.”

They sacrifice so much

It will be easy for us to just go about our normal routines this Friday, November 11, and not really consider all who have sacrificed so much to defend our country and fight the battles our government believes are worthwhile. Our current armed forces and our veterans are not the only ones who sacrificed something. Their families (mothers, fathers, siblings, spouses and children) also gave up so much. For example, service men and women as well as their spouses and children give up jobs, homes, schools, friends and a certain amount of security to serve. The spouses and children also have to live with the daily uncertainty of ‘if’ and ‘when’ they will be reunited again. Can you imagine what it is like for a child living with that uncertainty every day?

Service men and women come home today to an economy and job market that is scary to say the least. If they were seriously injured, the prospects for a normal life are even more difficult to comprehend. We need to ask ourselves whether we, as a nation, are serving our veterans as well as they have served us. I believe that answer is ‘NO’.

How can we help?

Some of you might not know where to get started. Read the online article, “11 Ways to Help Veterans.” It provides several opportunities to help.

Some ways are as easy as:

Giving a veteran a ride to a V.A. hospital.
Providing foster care for their pet.
Donating old cell phones and DVDs.
Cutting out food coupons (military families can use them for six months past the expiration date).

At the very least, they need to know that we are aware of what why and their loved ones sacrificed. You can do that by just shaking their hand and saying,

“Thank you for your service.”

Let’s start repaying our greatest national debt by honoring those who serve and have served.

Saturday, November 5, 2016

2016 Research Grants Awarded

The Kennedy’s Disease Association announced the recipients of the 2016 research Grants. The following projects have been awarded $50,000 each. Congratulations!

Dr Bilal Malik, Professor Greensmith’s Lab, UCL, Institute of Neurology, UK

Targeting pathways of disease in Spinal Bulbar and Muscular Atrophy (SBMA)

Spinal and Bulbar Muscular Atrophy (SBMA), also known as Kennedy’s disease (KD), is adult-onset slowly progressing rare inherited neuromuscular disorder that primarily affects males. As yet there are no effective treatments that can cure the disease or delay its progression. The disease is primarily characterized by muscle weakness and wasting, and degeneration of motor neuron cells within the spinal cord and brain.

Our aim is to establish why motor neurons and muscles degenerate in SBMA by investigating the genes and pathways that underlie disease. The identification of changes that occur early in disease may identify the mechanisms responsible for disease and help establish novel therapeutic targets. This proposal offers the unique opportunity to undertake a comparative study of two platforms that model SBMA, each with its own merits: i) a well-characterized mouse model in which muscle and motor neurons can be examined at various stages of disease, and ii) human cell models, including stem-cell derived motor neurons and patient muscle cells acquired from biopsies. By comparing and contrasting the changes in gene expression in these models of the specific cells affected in SBMA we hope to identify the key changes in gene expression that take place early in disease, identifying a common signature in the pathways of pathology. The results of this study will not only help define novel therapeutic targets with a greater level of confidence by analyzing several complimentary models of SBMA, but also allow us to test treatment strategies in a human cell model of the disease.

Dr. Janghoo Lim, Yale University School of Medicine

The role of VCP in the pathogenesis of Kennedy's disease

Spinal and Bulbar Muscular Atrophy (SBMA; Kennedy’s Disease) is a neuromuscular disease that affects motor neurons and skeletal muscles. The symptoms of SBMA include progressive weakness of the limbs and facial muscles, as well as difficulty with speaking and swallowing.  SBMA is an X-linked disease that primarily affects men, and is caused by a polyglutamine expansion in the gene Androgen Receptor (AR). The polyglutamine expansion in AR makes the protein toxic, and can lead to the formation of protein aggregates inside of cells as well as cell death. SBMA is one of nine different polyglutamine expansion disorders that are linked to neurodegeneration. How polyglutamine expanded AR causes SBMA is still being studied, and there are no effective therapeutics available. In order to better understand the mechanisms that cause SBMA and translate these results into the development of effective therapeutics, my proposal aims to assess how the protein Valosin-Containing Protein (VCP) is involved in SBMA.  VCP plays a role in breaking down mutant or damaged proteins, and has been studied in other neurodegenerative disorders. Based on our preliminary data, we hypothesize that VCP can regulate the expression and/or the activity of polyglutamine expanded AR. Our proposal will examine how VCP affects the development of protein aggregates and cell death in SBMA. We will use cell culture models and fruit flies, both of which are commonly used to study SBMA. This research will help develop a more thorough understanding of what causes SBMA, and provide important information when developing new therapeutics for this devastating disease.

Manuela Basso, Ph.D., Assistant Professor, Laboratory of Transcriptional Neurobiology, Centre for Integrative Biology, University of Trento, Italy

Insights into the molecular pathology of SBMA: Targeting PRMT6 to attenuate the disease

In collaboration with the Laboratory of Dr. Pennuto, we have recently discovered that a protein, called PRMT6, exacerbates the toxicity induced by mutant androgen receptor, while its inhibition rescues it in cells and flies. Our strategy is to develop a therapy that preserves AR physiological functions while abolishing the toxicity acquired upon polyglutamine expansion. Thus, we propose to silence PRMT6 both via selective pharmacological inhibitors and via gene-silencing to choose the best system to move our studies in pre-clinical models.

Thursday, November 3, 2016

Critical Illness and Long Term Disability

October 3rd I reported about Royal London Insurance adding Kennedy's Disease to their list of Critical Illness Coverage. I felt this was an important step and hoped other companies would follow in their footsteps.

This afternoon I read a nicely written piece on Royal London's goal of improving and simplifying the definitions of critical illnesses. Once again I applaud their efforts to improve the experience of customers shopping for this coverage.

You can read the entire article by following this link in Money Marketing: Enhance Simplicity.

Here is an excerpt of the article.

"Fortunately, things are improving with providers recognising the need to create simpler definitions. Earlier this month, we announced enhancements to our critical illness cover. The main change is to cancer cover; over 60 early stage cancers are now covered under nine definitions. By removing a long list of specified cancers, these changes provide clarity for advisers and customers and will result in more claims being paid.

In addition, our new Parkinson's definition now includes Parkinson's-plus syndromes that incorporate multiple system atrophy and progressive supranuclear palsy. Our motor neurone disease definition has been updated to include Kennedy’s disease, making the definition ABI+.

We could have listed numerous in situ cancers and shown Kennedy’s disease and the five Parkinson's-plus syndromes as stand-alone conditions but we didn’t want to play the numbers game."

On a personal note: Thirty years ago I took out disability insurance coverage while hoping I would never need it. Seventeen years later I was forced to go on long term disability. We were so thankful we had the coverage. It made making the difficult decision much more palatable.