SBMA Patients are More Likely to be Affected by Metabolic Disorders, Heart and Liver Disease

The following was reported in SMA News Today. The information is not new and from my perspective reflects mainly on the sedentary lifestyle after the progression has reached a point where the person can no longer perform aerobic physical exercise.

I believe it also reflects the need to continue to exercise (safely), change your diet, and be mindful of the possibility of these conditions in discussions with your doctor.

Heredity also plays an important factor in many of these conditions. 

SBMA Patients are More Likely to be Affected by Metabolic Disorders, Heart and Liver Disease

Patients with spinal-bulbar muscular atrophy (SBMA) are more likely to be affected by metabolic disorders, including insulin resistance and fatty liver disease, which can lead to heart disease and serious liver damage, a study says.

The study, “Prevalence of metabolic syndrome and non-alcoholic fatty liver disease in a cohort of Italian patients with spinal-bulbar muscular atrophy,” was published in Acta Myologica.

SBMA, also known as Kennedy’s disease, is a type of spinal muscular atrophy (SMA) that starts in adulthood and is characterized by widespread muscle weakness and wasting in the arms, legs, head, and neck (bulbar involvement).

The disorder is caused by mutations in the androgen receptor (AR) gene — located on the X chromosome — that lead to an abnormal expansion of a CAG nucleotide (the building blocks of DNA) repeat in the AR gene sequence and to the production of a much larger dysfunctional protein.

Besides neurologic symptoms, SBMA patients also tend to be affected by medical conditions associated with metabolic syndrome (a series of conditions that increase patients’ risk of developing heart disease, stroke or type 2 diabetes), such as insulin resistance, obesity, and glucose intolerance.

In the study, researchers at the University of Padua, in Italy, assessed the incidence of metabolic syndrome, insulin resistance, and non-alcoholic fatty liver disease (NAFLD) in a group of SBMA patients.

The study involved a total of 47 Italian patients with a confirmed diagnosis of SBMA who underwent a battery of biochemical tests to assess metabolic functions. A subset of 24 patients were examined by abdominal sonography (an imaging technique that allows physicians to visualize structures in the patients’ abdominal cavity).Results showed that 49% of the patients had abnormally high levels of fasting glucose (commonly used to diagnose diabetes), and 66% showed signs of insulin resistance.

In addition, 51% of the patients had high levels of total cholesterol, 38% had high LDL-cholesterol (“bad” cholesterol), and 38% had high triglycerides. Conversely, 77% had low levels of HDL-cholesterol(“good” cholesterol). More than half of the patients (55%) had three or more medical conditions associated with metabolic syndrome.

Researchers also found a positive relationship between insulin resistance and the length of CAG repeats in the AR gene sequence.

Biochemical tests showed high levels of two liver enzymes that, when elevated, may indicate liver inflammation or damage: aspartate transaminase (AST) levels were abnormally high in 62% of patients, and alanine transaminase (ALT) levels were high in 38% of patients.

Abdominal sonography revealed that 92% of the patients had liver steatosis (fatty liver disease) at different levels of severity, and one patient had liver cirrhosis (scarring of the liver).

“These alterations can be explained mainly by the reduction of testosterone activity because of (CAG repeats’) expansion in AR gene and must be considered as a main characteristic of Kennedy’s disease,” the researchers wrote.

“Metabolic alterations in SBMA are a suggestive model of androgen deprivation in male and require a multidisciplinary approach to disease. However, considering the conflicting data on the role of androgen stimulation in the metabolic involvement, further studies are needed to understand the pathogenesis of NAFLD and (insulin resistance) in SBMA patients and the possible detrimental consequences of anti-androgen approaches to disease,” they concluded.

Creatine Monohydrate Trial

I found this report on a trial conducted in 2014 and 15. I searched for the final analysis and can’t locate it. Perhaps you will have better luck than me. If so, let me know.

Treatment with Creatine Monohydrate in Spinal and Bulbar Muscular Atrophy: Protocol for a Randomized, Double-Blind, Placebo-Controlled Trial

Yasuhiro Hijikata, MD, PhD, Masahisa Katsuno, MD, PhD, Keisuke Suzuki, MD, PhD, Atsushi Hashizume, MD, PhD, Amane Araki, MD, PhD, Shinichiro Yamada, MD, PhD, Tomonori Inagaki, MD, Daisuke Ito, MD, Akihiro Hirakawa, PhD, Fumie Kinoshita, MSc, Masahiko Gosho, PhD, and Gen Sobue, MD, PhD

Background

Although spinal and bulbar muscular atrophy (SBMA) has been classified as a motor neuron disease, several reports have indicated the primary involvement of skeletal muscle in the pathogenesis of this devastating disease. Recent studies reported decreased intramuscular creatine levels in skeletal muscles in both patients with SBMA and transgenic mouse models of SBMA, which appears to contribute to muscle weakness.

Objective

The present study aimed to examine the efficacy and safety of oral creatine supplementation to improve motor function in patients with SBMA.

Results

Participant enrollment in the trial started from June 2014 and follow-up was completed in July 2015. The study is currently being analyzed.

Kennedy's Disease - Beyond Motor Neurons

The link below opens a recent study published in the Journal of Neurology, Neurosurgery & Psychiatry. It explains SBMA (Kennedy’s Disease) very well. The report is not just focused on the motor neurons. It goes into detail explaining other aspects of the condition and other potential opportunities for a treatment.

Beyondmotor neurons: expanding the clinical spectrum in Kennedy’s disease

Raquel Manzano, Gianni Sorarú, Christopher Grunseich, Pietro Fratta, Emanuela Zuccaro, Maria Pennuto, Carlo Rinaldi

“…Compared with other motor neuron diseases, such as amyotrophic lateral sclerosis (ALS), disease progression is relatively slow, with muscle strength declining by 2% per year. Recent evidence has shown that the muscle atrophy in SBMA is not solely secondary to the motor neuron degeneration but also consequence of a primary myopathic process. In addition, SBMA is frequently complicated by other signs and symptoms such as gynaecomastia, impotence, testicular atrophy and metabolic changes, suggesting a multisystem involvement in the disease. These features frequently manifest early in the disease course and can contribute substantially to the morbidity. In this review, we discuss the non-motor neuron abnormalities underlining SBMA symptomatology. We propose that an improved understanding of these features not only could result in better management of the patients SBMA, but also has the potential to shed new light into the disease pathogenesis, lead to the discovery of biomarkers for disease progression and open new treatment avenues. …”

“… Motor neurons are particularly sensitive to alterations in the proteostasis network, likely due to their extreme polarisation and post-mitotic nature. On the other side, alterations of protein quality control in muscle, by tilting the balance towards increased protein degradation, are likely the underlying cause of the muscle atrophy observed in this disease. …”

I feel this information should be shared with your primary care doctors. It might help explain other symptoms not normally associated with Kennedy’s Disease.

Swallowing markers in spinal and bulbar muscular atrophy

This article was posted on August 17. I have been busy engaged in publishing my latest book, so I did't have a chance to review it before today. Those of us living with Kennedy's Disease often experience problems with swallowing and choking. This article explains the research findings on KD patients and swallowing.You can read the entire article by clicking on the header below.


Swallowing markers in spinal and bulbar muscular atrophy

Swallowing markers in spinal and bulbar muscular atrophy.

Ann Clin Transl Neurol. 2017 Aug;4(8):534-543

Authors: Banno H, Katsuno M, Suzuki K, Tanaka S, Suga N, Hashizume A, Mano T, Araki A, Watanabe H, Fujimoto Y, Yamamoto M, Sobue G

Abstract

OBJECTIVE: We examined the characteristics of dysphagia in spinal and bulbar muscular atrophy, a hereditary neuromuscular disease causing weakness of limb, facial, and oropharyngeal muscles via a videofluoroscopic swallowing study, and investigated the plausibility of using these outcome measures for quantitative analysis.

METHODS: A videofluoroscopic swallowing study was performed on 111 consecutive patients with genetically confirmed spinal and bulbar muscular atrophy and 53 age- and sex-matched healthy controls. Swallowing of 3-mL liquid barium was analyzed by the Logemann’s Videofluorographic Examination of Swallowing worksheet.

RESULTS: Of more than 40 radiographic findings, the most pertinent abnormal findings in patients with spinal and bulbar muscular atrophy, included vallecular residue after swallow (residue just behind the tongue base), nasal penetration, and insufficient tongue movement (P < 0.001 for each) compared with healthy controls. Quantitative analyses showed that pharyngeal residue after initial swallowing, oral residue after initial swallowing, multiple swallowing sessions, and the penetration-aspiration scale were significantly worse in these patients (P ≤ 0.005 for each) than in controls. ...

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There is another article on a 2014 study on tongue pressure in patients with KD. It can be found here:

Tongue pressure as a novel biomarker of spinal and bulbar muscular atrophy.

Image from YouTube video

New Treatment for SBMA Approved in Japan

Since the initial announcement in mid-August, there has been a lot of buzz about this treatment. Mike Wilson posted the following translation on the KD-Downunder Facebook page. The comments posted from others living with KD is interesting.

The article he is referring to can be found at http://www.takeda.co.jp/news/2017/20170828_7818.html  When this trial was first introduced back in 2010, I posted an article on it. You can read it here. This month I posted the announcement about the long-term trial results. It can be found here.  

Interesting news - A new treatment for SBMA just approved in Japan:

Leuplin SR® Injection Kit 11.25 mg in Japan

About supplemental approval of indication of "suppression of progression of spinal and bulbar muscular atrophy"

We are pleased to announce that "Spinal and Bulbar Muscular (Spinal and Bulbar Muscular Disease)" from the Ministry of Health, Labor and Welfare for "Leuprin® SR Injection Kit 11.25 mg" (generic name: leuprorelin acetate, We are pleased to announce that we have received additional indication of the suppression of the progression of "Atrophy: SBMA").

Leuplin SR is a 12-week sustained-release sustained-release preparation of highly active LH-RH agonist (luteinizing hormone-releasing hormone derivative) synthesized by Sumitomo Chemical, which acts continuously on the pituitary gland, It inhibits the production of sex hormones by reducing reactivity. This drug is used as a therapeutic agent for hormone dependent diseases such as prostate cancer and premenopausal breast cancer in Japan.

The acquisition of additional indication for the indication was mainly evaluated based on the results of doctor-initiated trials that examined the effectiveness and safety of Leuplin SR for patients with SBMA, centering on Nagoya University neurology department. It is world's first approval as a therapeutic agent for the progression of SBMA.

Toshiro Taniya, director of the Company's Japan Development Center, said, "To date, no effective treatment for SBMA has been established domestically and internationally, and drugs that could contribute to the treatment of this disease were sought. , It will become the world's first medicine to be useful in treating patients of SBMA.We appreciate the patients and doctors who cooperated in developing this drug, and for the patient and medical staff We will strive to deliver medicines for diseases with high unmet medical needs. "

About indications / effects, dosage and dosage approved this time

Indications and effects: inhibition of progression of spinal and bulbar muscular atrophy

Dosage / administration: Usually, adults receive 11.25 mg subcutaneously as Leuprorelin acetate once every 12 weeks.

Upon administration, push the plunger rod with the injection needle facing upward, move the whole amount of the suspension liquid to the powder part, and carefully suspend and use it while taking care not to foam.

About SBMA

SBMA is characterized by muscle atrophy and is an X-linked lower motor neuron disease that develops in adult male. Due to abnormal accumulation of mutant androgen receptor (AR) with polyglutamine in the nucleus, an androgen hormone dependent neuronal damage occurs. It usually develops around 30 to 60 years old, it follows a slow progressive course, not only forced to live in bed chair or bedridden life at the end of the year, but also repeats aspiration pneumonia. In Japan, it is stipulated as a designated intractable disease, and it is reported that the number of persons with specific medical care recipient 's passengers is 1,223 (Research on Specific Diseases by Ministry of Health, Labor and Welfare in FY2006).

Long-term treatment with leuprorelin for spinal bulbar muscular atrophy

A gentleman living with Kennedy's Disease sent me the following email. I remember the initial trial years ago, but I wasn't aware researchers continued it. The link for the actual study is at the bottom of his message. I forwarded this to Dr. Fischbeck to see if he has any thoughts on the study.

In a conversation for Dr. Fischbeck several years ago, he mentioned the difficulty of measuring results in short term clinical studies because SBMA progresses slowly. This study is 84-months long and I assume is easier to quantify the results.


Long-term treatment with leuprorelin for spinal and bulbar muscular atrophy: natural history-controlled study
"Recently they published a new, interesting study about long term therapy of SBMA. It is an old candidate: leuprorelin. As you may know, there were two previous (phase 2 and 3) trials with leuprorelin, done in Japan, the second one is the JASMITT study. After continuing the treatment of 36 patients from the previous studies, the same researcher group have now new data with leuprorelin.

1. They have data from 84-months follow-up, with hard endpoints. 
2. They showed significant difference in several functional scores, compared to no-drug controll. 
3. Maybe most importantly, there was a significant difference in the event-free survival (death or pneumonia). The similar trend was in the risk of death, however it was not significant, they suppose because of the low statistical power (i.e. number of patients) of the study, and the slow progression of the SBMA. However, pneumonia is a very important event in SBMA since aspiration is one of the biggest, deadly threat in this disease. 
4. The final conclusion from the article: "In conclusion, this study showed that the continuous administration of leuprorelin acetate appears to slow the progression of motor deficits in subjects with SBMA. In addition, pneumonia-free survival in SBMA would be extended by long-term treatment with leuprorelin acetate, suggesting disease-modifying effects of androgen deprivation by leuprorelin acetate."

As far as I know, it is one of the longest, controlled trial in patients with SBMA. I think we may reconsider the therapeutic possibilities of antiandrogens, and I guess we will hear about in the near future. It would be nice to know Dr. Fischbeck's comments.

It is important to keep in mind that everyone have to talk his physician first.

Here is the abstract of the article: http://jnnp.bmj.com/content/early/2017/08/05/jnnp-2017-316015 , unfortunately the full-text version is not free-access."
Note:  The original post on the trial can be found here:  Leuprorelin

Possible new therapy for motor neuron diseases

The University of Sheffield published the following news release yesterday. As always, additional research is required, but the premise is interesting.

New discovery in motor neurone disease and dementia could pave the way to novel treatments

"... When this series of nucleotides is expanded and repeated multiple times, neurodegenerative diseases can occur. The expansions of the gene forms genetic material called ‘R-loops’ which make the DNA vulnerable to breakages. They found that accumulation of R-loops and increased DNA breakage in neurons lead to neurodegenerative diseases.

Our cells have their own repair toolkits specially designed to fix breaks in DNA, however, the products of the expansion over-activate a process called autophagy – a process that gets rid of misfolded or “unwanted” proteins.

The new study, jointly directed by Professor Sherif El-Khamisy from the University of Sheffield’s Department of MBB and Professor Mimoun Azzouz from SITraN at the University of Sheffield, published today (17 July 2017) in Nature Neuroscience, shows that the expansion driven over-activation of this process can degrade some of the very precious DNA toolkits, meaning the cells will eventually die.

“We were able to shut down the out-of-control degradation process, which runs down the cell’s ability to fix genomic breaks, using genetic techniques,” said Professor El-Khamisy.

“Even though the DNA was still damaged, the cells were able to cope and did not die. Discovering this new mechanism and its consequence is a significant step towards developing new therapies for motor neurone disease and other neurodegenerative conditions. ..."

Click on the title to read the entire article.

Respiratory Issue with SBMA

SMA News Today published an article on respiratory issues with patients with Kennedy's Disease. A portion of the article as well as a link to the full article and actual study results are shown below. Most of us are aware of this issue; especially the implications of pneumonia and KD.




SBMA Patients Prone to Develop Respiratory Problems Due to Reduced Muscle Strength, Study Says


Patients with spinal and bulbar muscular atrophy (SBMA) may be at risk of developing respiratory complications due to a decline in the levels of genes responsible for muscle strength, according to a new study. The authors assert that monitoring the breathing decline in these patients may help provide better clinical management of the disease.

The study, “Decreased Peak Expiratory Flow Associated With Muscle Fiber-Type Switching In Spinal And Bulbar Muscular Atrophy,” was published in the journal PLoS One.

At more advanced stages of the disease, SBMA patients may develop dysphagia (difficulties in swallowing) and dyspnea (shortness of breath), as well as pneumonia and respiratory failure. Thus, the management of swallowing and respiratory function is indispensable for the long-term care of these patients.

However, respiratory difficulties associated with SBMA are not well characterized, which limits the knowledge of how these processes occur in patients and how they might be managed.

The objective of the study was to evaluate respiratory function of SBMA patients and identify the mechanisms underlying this condition, in comparison to patients with amyotrophic lateral sclerosis (ALS), another motor neuron disease in which dyspnea has been observed and well-studied.

The study included 40 SBMA and 25 ALS male patients, as well as 15 healthy individuals, in whom researchers evaluated respiratory function (by assessing the peak expiratory flow, %PEF, a measure of breathing capacity, and the forced vital capacity, FVC), ....

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.”

Non-neural phenotype of spinal and bulbar muscular atrophy

Below is an abstract of a research paper published last year. This study was focused on non-neurological characteristics in 73 patients with Kennedy’s Disease. 

“Non-neurological clinical features have not been extensively investigated in previous reports. The aim of the present study was a deep characterisation of the involvement of the main androgen-responsive tissues in a large collection of patients with SBMA. The findings highlight novel non-neural dysfunctions and a wide phenotypic spectrum, suggesting the need for a comprehensive, multidisciplinary approach to SBMA.

Abstract

Objective To carry out a deep characterisation of the main androgen-responsive tissues involved in spinal and bulbar muscular atrophy (SBMA).

Methods 73 consecutive Italian patients underwent a full clinical protocol including biochemical and hormonal analyses, genitourinary examination, bone metabolism and densitometry, cardiological evaluation and muscle pathology.

Results Creatine kinase levels were slightly to markedly elevated in almost all cases (68 of the 73; 94%). 30 (41%) patients had fasting glucose above the reference limit, and many patients had total cholesterol (40; 54.7%), low-density lipoproteins cholesterol (29; 39.7%) and triglyceride (35; 48%) levels above the recommended values. Although testosterone, luteinising hormone and follicle-stimulating hormone values were generally normal, in one-third of cases we calculated an increased Androgen Sensitivity Index reflecting the presence of androgen resistance in these patients. According to the International Prostate Symptom Score (IPSS), 7/70 (10%) patients reported severe lower urinal tract symptoms (IPSS score >19), and 21/73 (30%) patients were moderately symptomatic (IPSS score from 8 to 19). In addition, 3 patients were carriers of an indwelling bladder catheter. Videourodynamic evaluation indicated that 4 of the 7 patients reporting severe urinary symptoms had an overt prostate-unrelated bladder outlet obstruction. Dual-energy X-ray absorptiometry scan data were consistent with low bone mass in 25/61 (41%) patients. Low bone mass was more frequent at the femoral than at the lumbar level. Skeletal muscle biopsy was carried out in 20 patients and myogenic changes in addition to the neurogenic atrophy were mostly observed.

Conclusions Our study provides evidence of a wide non-neural clinical phenotype in SBMA, suggesting the need for comprehensive multidisciplinary protocols for these patients.”

The full article can be found here:  http://jnnp.bmj.com/content/early/2015/11/05/jnnp-2015-311305.full?sid=d584bac7-cae4-4d14-9047-84fd5e49d918

Apps to monitor and report on your health.

The below link to an article in HuffPost Healthy Living by Brandon Bailey of the Associated Press was posted in the KDA Forum. 

These type apps could be beneficial those of us living with Kennedy's Disease (SBMA) who have difficulty traveling to NIH or other distant research facilities. It appears the apps could be used to monitor certain clinical trial information including progression, side effects, gait, etc. This would have been useful for the clinical trial on exercising also. 

The article mentions that people are more involved in the studies because of these apps. They have some control and are needed to participate to monitor and send the information being collected.It was interesting to me that over 75,000 people have enrolled in studies using these type apps. 

I can see where this would be great for many studies where normally you would have to return to the hospital, doctor's office, or research facility to be tested or evaluated regularly. I would think that another benefit is the data can be more easily collected, stored and analyzed..

Of course, the comment on maintaining the privacy of the user and the information reported is still something that is a concern.

Check it out and let me know what you think. Thanks

This Phone App Lets You Contribute To Research On Your Own Disease

Study of Hepatic Function in Patients With Spinal and Bulbar Muscular Atrophy

NIH has scheduled another study and are currently recruiting patients.  Link to NIH website  You can read more about it on the KDA website (June 07, 2014 Chat).
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Background:
- Spinal and bulbar muscular atrophy (SBMA) is an inherited disease. It causes weakness in muscles used for swallowing, breathing, and speaking. SBMA mainly affects men, but women can carry the gene for it. Researchers think there may be a link between SBMA and excess fat in the liver.

Objective:
- To look for fatty liver and liver injury in people with SBMA, people with motor neuron disease, and people who carry the gene for SBMA.

Eligibility:

• Adults 18 years and older who have SBMA, have motor neuron disease, or are carriers of SBMA.
• Healthy adult volunteers.

Design:

• Participants will be screened with medical history, physical exam, and blood tests.
• Participants will have 1 outpatient visit of 1-2 days. Women will have a urine pregnancy test. All participants will have:
• Blood tests.
• Liver ultrasound. A probe is placed on the abdomen at certain locations and angles and takes pictures. The painless procedure takes 20-30 minutes.
• Liver magnetic resonance imaging (MRI) scan. The MRI scanner is a metal cylinder with a magnetic field. Participants will lie on a table that slides in and out of it. They will be in the scanner for about 30 minutes. They will get earplugs for loud noises.
• Some participants with abnormal liver testing will have a biopsy (small piece) of the liver taken. The biopsy site will be located with ultrasound, then cleaned and numbed. The physician will quickly pass a needle in and out of the liver while the participants holds their breath. Afterward, participants will be monitored in bed for 6 hours.
• Participants may return for follow-up and another 1-2 day outpatient visit yearly for up to 2 years.

The difficulty with finding a cure

Ed, our resident biology professor and research guru, posted the following response to a KDA Forum question on why finding a treatment or cure for Kennedy’s Disease and other neuromuscular diseases is so difficult. Ed did such a fine job of clarifying the problem I thought that others should have the opportunity to read his response.

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Reference medical research on neuromuscular diseases, no one has yet determined exactly why the cells die in such diseases, much less how to stop the cell death. This is not due to lack of money, effort, organization or urgency, but because it is a very, very difficult problem. Each cell has thousands of machine-like molecules called proteins and each protein has a specific function in the cell. Of these thousands of proteins, it is not obvious which are important for keeping the cell working properly – or even how they keep the cell working properly.

Within the brain alone, there are thousands if not millions of different types of cells, each with their own function and specific set of proteins. Kennedy's Disease (or Parkinson Disease or Huntington Disease or ALS etc.) all cause a small subset (and this subset is different in each disease) of these cells to die. It is not understood what specifically makes each cell type different or why only some neurons die in each of these diseases or, in fact, why any nerve cells die in these disease. It is very difficult to find a cure for Kennedy's Disease when it is not even understood why the cells die. 

One of the first steps to understanding why a cell dies in Kennedy's Disease is to understand how the cell works – thus understanding the role of each of the proteins in the cell. We do know that in Kennedy's Disease, the defect is originally in the protein called the Androgen Receptor (AR) and somehow (no one knows how despite extensive research) this leads to some specific nerves cells to die. To figure out the molecular cause, it is necessary to figure out all the possible interactions that AR can have and try to identify the one that causes the cells to die. The AR interacts with hundreds of other proteins.  Which of these interactions is relevant for Kennedy's Disease? No one yet knows. This is akin to finding a specific hay strand in a haystack – it is a very difficult problem and despite our wishes, it takes time to work this out.

There is another issue that needs to be understood. Suppose that someone develops a treatment for Kennedy's Disease tomorrow. What would this treatment do? Most likely, it would prevent the nerve cells from dying. It is extremely unlikely, however, that it would regenerate new nerve cells (this is technology that is quite futuristic). Thus, those of us with Kennedy's Disease that has progressed will not have our symptoms reversed – we would just stop the current downward progression. While this would be a tremendous development, we would still have Kennedy's Disease symptoms. 

Two Important Kennedy’s Disease Studies Revisited

Back in 2010 I wrote articles on two important Kennedy’s Disease studies. For my newer readers, these two studies are still important reads to help understand Kennedy’s Disease and its effect on anyone with the mutated gene.

The Natural History of Kennedy’s Disease

I believe this is one of the most complete studies on what happens when it happens to a patient with Kennedy’s Disease. I summarized the report in my original article:

"Fortunately, this study is well written … meaning I could understand it.  This is the only study that I am aware of that focuses in on what happens and when does it occur.  It is based upon data provided for up to twenty years of a patient’s life.  This study is different than most, because of the number of patients.  So often the patient base is substantially smaller.  I would recommend reading the article if you want to learn more about the onset and progression of Kennedy’s Disease.  Little time is given to the cause of Kennedy’s Disease or current research if that is your interest."

Below are the links to my articles on this report:
http://kennedysdisease.blogspot.com/2010/05/natural-history-of-kennedys-disease.html
http://kennedysdisease.blogspot.com/2010/05/being-53-is-not-excuse.html
http://kennedysdisease.blogspot.com/2011/04/natural-history-of-kennedys-disease.html


The key findings in this study were:

1. The greater the size of the CAG-repeat expansion (CAG count), the earlier the onset.  The study used nine ADL’s (activities of daily living*) for milestones in this study
2. The rate of disease progression was not dependent upon the number of CAG-repeats. 
3. The researchers commented that the most striking observation was that the CAG-repeat length did not affect the interval periods between the individual ADL milestones.  In other words, the progression of the disease is not influenced by the CAG count. 
4. The most common cause of death was pneumonia due to aspiration and dysphagia.  Even though these two bulbar symptoms were relatively mild when first manifested, they were serious issues in the later phases of the disease. 
5. Creatine kinase (CK) averaged 863 in these patients with a range from 31 to 4955. The normal range for CK is 45 to 245.
6. Serum testosterone levels were relatively high even with older patients, although the levels did decrease with age.

Clinical Features of Spinal and Bulbar Muscular Atrophy

The other recent study goes in a somewhat different direction, but is also very helpful in understanding the disease. I summarized the report in my original article:

“In October of last year, a paper was published on the findings of 57 patients with Kennedy's Disease here in the United States. It is somewhat different in scope than the "Natural History of SBMA" report I discussed in May. The information provided in this report was obtained during the last NIH clinical trial. The title of this report is "Clinical Features of Spinal and Bulbar Muscular Atrophy." In today's article I will highlight certain findings that I found interesting. I would recommend that if you are interested, please follow the link above and read the entire paper.”

Below is the link to my article on this report:
http://kennedysdisease.blogspot.com/2010/06/clinical-features-of-kennedys-disease.html

"This report concluded that the longer the CAG repeat length (number), the earlier the onset. It also commented that the longer the CAG repeat length, the greater the abnormalities in motor and sensory nerve conduction. 94-to-100% of the patients had some sensory problems. They reported that there was a significant difference in the MUNE (motor unit number estimation) between SBMA subjects and the control (healthy) group. This sensory nerve issue (nerve conduction) has been one that has bothered many of us with Kennedy's Disease for some time. The tingling or numbness in the feet, hands or other parts of the body has been frustrating, because it had not been reported as a symptom until recently."

If you haven’t visited these articles or read the actual reports, I would recommend that you take the time to do so.