Monday, October 16, 2017

Huntington’s Disease: Gene Editing Shows Promise in Mouse Studies

This is another article snipped from the NIH.gov blog. Since Huntington’s and Kennedy’s Disease  both have extra repetitions of the CAG DNA, this is another advancement in treating and possibly curing these type diseases. As I mentioned in my previous post, the process is still experimental, but it is moving in the right direction. If you haven't read the previous update on gene editing, you can find it here.


To read the entire article, click on the title below.

Huntington’sDisease: Gene Editing Shows Promise in Mouse Studies

Posted on June 27, 2017 by Dr. Francis Collins

“…But years of basic science advances, combined with the promise of innovative gene editing systems such as CRISPR/Cas9, are providing renewed hope that we will someday be able to treat or even cure Huntington’s disease, along with many other inherited disorders.

My own lab was part of a collaboration of seven groups that identified the Huntington’s disease gene back in 1993. Huntington’s disease occurs when a person inherits from one parent a mutant copy of the huntingtin (HTT) gene that contains extra repetitions, or a “stutter,” of three letters (CAG) in DNA’s four-letter code. This stutter leads to production of a misfolded protein that is toxic to the brain’s neurons, triggering a degenerative process that, over time, leads to mood swings, slurred speech, uncontrolled movements, and, eventually, death. In a new study involving a mouse model of Huntington’s disease, researchers were able to stop the production of the abnormal protein by using CRISPR tools to cut the stutter out of the mutant gene.

The progress, reported in the Journal of Clinical Investigation [1], comes from the NIH-supported team of Su Yang, Renbao Chang, Xiao-Jiang Li, and colleagues at Emory University School of Medicine, Atlanta. The group’s previous work showed that halting the production of mutated (or even healthy!) HTT protein in mature neurons doesn’t hurt the cells or cause obvious neurological problems in mice [2]. So, the researchers now wanted to see if halting HTT production in millions of neurons in the striatum, which is a part of the inner brain that controls motor skills, could reverse early signs of disease that typically appear in affected mice before the age of 9 months.

To get their answers, the researchers injected millions of inactivated viral particles directly into the striatum of a few 9-month-old mice, engineered to produce the mutant form of HTT protein. Each particle, like a Trojan horse, delivered to the neurons one of the two pieces of the CRISPR/Cas9 editing system: either a short guide RNA sequence to mark for removal the HTT gene’s CAG repeats or a scissor-like Cas9 enzyme to snip out the repeats. In this strategy, both the health and abnormal copies of the HTT gene were “knocked out,” resulting in the production of no HTT protein.

Remarkably, three weeks later, the researchers found that the CRISPR/Cas9 gene editing had reversed the disease process in their mouse model. Neurons in the striatum had stopped making the HTT protein. What’s more, the toxic, abnormal HTT protein that had already clumped together in and around the neurons—and which likely would have would have killed them—had begun to clear to varying degrees in the mice. The same went for other protein abnormalities associated with the progression of Huntington’s disease.

There was even better news to come. The Emory team repeated the CRISPR/Cas9 injections into the striatum of a dozen 9-month-old mice and got a similar protein-clearing outcome. Then, over the next three months, the researchers found that the animals’ balance, muscle coordination, and mobility had improved compared to mice given sham shots of CRISPR/Cas9. Interestingly, the degree of improvement in their motor skills corresponded with the amount of toxic protein that had been cleared from the striatum…”


“…This utilization of CRISPR/Cas9 to pursue a cure for Huntington’s disease is one more example of how this powerful new technology might be applied to the thousands of diseases due to a specific mutation in DNA; efforts are already underway for other conditions like sickle cell disease and muscular dystrophy. Given the promise, the NIH Common Fund is actively exploring ways in which this approach could be accelerated.”

Gene Editing: Gold Nanoparticle Delivery Shows Promise

The following article was snipped from NIH.gov’s blog. It describes another improvement in the gene editing research going on around the world. The process is still experimental, but it is moving in the right direction. Read my next article on Huntington's Desease. Kennedy's Disease could be right around the corner. 


To read the entire article, click on the title below.

GeneEditing: Gold Nanoparticle Delivery Shows Promise


Posted on October 10, 2017 by Dr. Francis Collins

…”NIH-funded researchers have developed a highly versatile approach to CRISPR/Cas9-based therapies. Instead of relying on viruses to carry the gene-editing system into cells, the new approach uses tiny particles of gold as the delivery system!

In order to fix a disease-causing mutation like the expanded DNA repeat that causes FA (Friedreich’s ataxia), researchers must create a CRISPR/Cas9 system that contains a scissor-like Cas9 enzyme and a synthetic guide RNA, which steers Cas9 to the specific part of the genome that needs to be snipped out. If a very precise correction is to be made, a repair template that contains the desired DNA code must also be included.

The challenge is delivering all these components into the appropriate tissues in a safe and efficient manner. Currently, most researchers use inactivated, non-disease-causing viruses to ferry various parts of the CRISPR/Cas9 system into cells. However, because of size constraints, it’s not possible to fit all three components into a single virus. Also, because of the large number of viral particles needed to carry CRISPR/Cas9 components in separately, there are concerns that viral delivery systems could trigger immune responses in people. Not only could such immune responses pose a safety hazard to patients, they could also reduce the effectiveness of the viral delivery system.

Because of these challenges, there’s been great interest in developing better ways to deliver CRISPR/Cas9 therapeutics. In the new study recently reported in Nature Biomedical Engineering, Irina Conboy and Niren Murthy at the University of California, Berkeley, decided to try a delivery vehicle they call CRISPR-Gold [1].

Gold might seem like an odd choice, but gold nanoparticles possess a special ability to penetrate cell membranes and have been considered for use in delivering therapies for cancer, rheumatoid arthritis, and many other conditions. In addition, gold is generally well tolerated by the human body and has the advantage of linking easily to DNA.

The CRISPR-Gold system—which consists of a DNA-linked gold nanoparticle containing Cas9, guide RNA, and a DNA repair template—is designed to enter cells through endocytosis, a process in which the cell engulfs outside molecules. A special polymer that encases the CRISPR-Gold system helps to ensure the gene-editing tools reach the cell’s genome in an active state.

In a series of tests, the researchers showed that CRISPR-Gold could enter a variety of cell types in laboratory culture, including immune cells, muscle cell progenitors, human induced pluripotent stem cells, and human embryonic stem cells. Once inside the cells, CRISPR-Gold could successfully find and edit a target gene in a non-toxic manner. Similar success occurred when CRISPR-Gold was injected into the muscles of living lab mice.

The next big challenge was to test CRISPR-Gold’s potential in a model of human disease. So, researchers turned to a mouse model of Duchenne muscular dystrophy (DMD), a fatal disorder characterized by progressive muscle weakening and caused by a mutation in the gene that codes for the protein dystrophin. They injected CRISPR-Gold containing a template for a healthy dystrophin gene into the leg muscles of young DMD mice. At the same time, they injected a toxin intended to encourage muscle cells to multiply because, for CRISPR editing to work optimally, cells must be actively dividing.

The outcome was encouraging. After one injection of CRISPR-Gold, about 5 percent of the dystrophin genes in the muscle tissue of the DMD mice had been corrected. What’s more, the animal’s muscles produced functional dystrophin protein, and they performed better on tests of muscle strength.

There was also good news on the safety front. The DMD mice didn’t appear to have a strong immune reaction to the treatment. The researchers also didn’t find evidence that CRISPR-Gold caused much, if any, unintended “off target” damage to the animals’ DNA.

Taken together, the findings suggest that, pending further replication, optimization, and careful testing, CRISPR-Gold might have promise for treating humans with DMD.


What makes this approach especially exciting is that it also holds potential for treating or even curing many other genetic diseases …”

Thursday, October 5, 2017

Scientists create new motor neurons out of skin cells

I found the link to this article on the Kennedy’s Disease DownUnder Facebook page. You can read the entire article by clicking on the Title below. The ability to reproduce motor neurons that are the age of the patients could be helpful in studying the progression as well as potential treatments.

Scientists create new motor neurons out of skin cells



“… Scientists have converted human skin cells from adults directly into motor neurons without going through a stem cell state.

Motor neurons drive muscle contractions, and their damage underlies devastating diseases such as amyotrophic lateral sclerosis and spinal muscular atrophy, both of which ultimately lead to paralysis and early death. Scientists working to develop new treatments for neurodegenerative diseases have been stymied by the inability to grow human motor neurons in the lab.” …

“… The new technique makes it possible to study motor neurons of the human central nervous system in the lab. Unlike commonly studied mouse motor neurons, human motor neurons growing in the lab would be a new tool since researchers can’t take samples of these neurons from living people but can easily take skin samples.

Avoiding the stem cell phase eliminates ethical concerns raised when producing what are called pluripotent stem cells, which are similar to embryonic stem cells in their ability to become all adult cell types.” …

Importantly, avoiding a stem cell state also allows the resulting motor neurons to retain the age of the original skin cells and, therefore, the age of the patient. Maintaining the chronological age of these cells is vital when studying neurodegenerative diseases that develop in people at different ages and worsen over decades.

“… In this study, we only used skin cells from healthy adults ranging in age from early 20s to late 60s,” says senior author Andrew S. Yoo, an assistant professor of developmental biology at Washington University School of Medicine in St. Louis. “Our research revealed how small RNA molecules can work with other cell signals called transcription factors to generate specific types of neurons, in this case motor neurons. In the future, we would like to study skin cells from patients with disorders of motor neurons. Our conversion process should model late-onset aspects of the disease using neurons derived from patients with the condition.” …


“…The ability of scientists to convert human skin cells into other cell types, such as neurons, has the potential to enhance understanding of disease and lead to finding new ways to heal damaged tissues and organs, a field called regenerative medicine. …”

Monday, September 25, 2017

It's Never too Late


The quote below is taken from Eric Roth who adapted the script for the movie, "The Curious Case of Benjamin Buttons." The scene is "The letter to Caroline." I have changed a few words to make it more focused for my message about 'LIFE.".

     It’s never too late to be whoever you want to be.
     There's no time limit. Start whenever you want.
     You can change or stay the same.
     There are no rules to this thing.
     You can make the best or the worst of it.

     I hope you make the best of it.
     I hope you see things that startle you.
     I hope you feel things you never felt before.
     I hope you meet people who have a different point Of view.
     I hope you live a life you're proud of, and if you're not,
     I hope you have the courage to change it.


The above is a powerful statement of our ability to make a difference in the world. The Kennedy’s Disease Association and its website is one example. The Kennedy’s Disease Facebook Groups are other examples. There are also many other individuals who found ways to help those of us seeking answers or needing hope. And, we all need hope.  

The good news…


It is never too late—that is the important message. It gives us hope. 


FYI - you might enjoy reading this blog post on it never being too late

Saturday, September 23, 2017

Feel Good Drug


I guess you could say I am addicted. First thing every morning I need to have it. Afterward, everything is good—
Real Good

Now I can face the day.

Every evening, I need another fix to 'smooth things out'. Now I am ready for a good night’s sleep.

If you know me or read my blog regularly, you know I am talking about my daily exercise routine. When I exercise, my body releases chemicals called endorphins. “Endorphins are among the brain chemicals known as neurotransmitters, which function to transmit electrical signals within the nervous system. They are morphine-like chemicals produced by the body that help diminish pain while triggering positive feelings. Endorphins are sometimes referred to as the brain's "feel-good" chemicals, and are the body's natural painkillers.”(1)

For a long time I did not know meditation also releases endorphins. I guess that is why I became hooked on meditation many years ago. I also read chocolate and chili peppers will release them. Who would have ‘thunk it’?




I do not mind being called an “endorphin junky.” I could be called a lot worse.

Once again, it shows that we need to be stewards of our mental, emotional and physical health.

Living with Kennedy's Disease requires me to be at my best every day. I had my fix for the day. How about you?


Photo:  https://www.fastcompany.com/3025957/

Sunday, September 17, 2017

Unexpected Benefit


In June, I noticed my pinky finger on the left hand felt numb. I tried several exercises, but the sensation was still there. About a month later, I noticed the right pinky finger was a little number. It was not as pronounced as the left, but still noticeable.

For several years, the bottoms of my feet and toes have been numb or tingly. I tried different techniques to stimulate the nerves, but nothing seemed to work. In early August, the feet were particularly bad. One evening, I used my hands to massage my feet. The feet were more sensitive than I thought they would be when I performed a deep tissue massage. At times, it was slightly painful. Yet, they felt better.

I kept up the evening massages and noticed a positive pronounced difference in regards to sensations. The tingling and numb feeling is barely noticeable. The toes also have more feeling. By the end of August, something else became apparent. I no longer had the number feeling in the pinky fingers on both hands.


It is mid-September and the bottoms of my feet and my toes are remarkably better. I have not experienced the numbness in my fingers for at least three weeks. I will continue my evening massages and let you know if anything changes. But, for now, I like the results.


Monday, September 11, 2017

Patients with Mesothelioma

I don't normally post topics other than those related to progressive motor neuron conditions and resources, but Virgil Anderson, a cancer survivor, asked if he could post something on my blog. Since cancer has become an intruder in the lives of family and friends, I decided to post his article,
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Resources for Patients with Mesothelioma


Mesothelioma is a terrible type of cancer because it is aggressive, spreads quickly, and is often diagnosed in the later stages, when treatment options are limited. But getting a mesothelioma diagnosis does not have to come with no hope. There are resources available for those who need them, and these include medical, legal, and financial resources.

Medical Resources for Mesothelioma
Mesothelioma is a cancer that most often attacks the pleura, the two layers of tissue surrounding the organs of the chest cavity. It is most commonly caused by exposure to asbestos and has a long latency period, so that by the time a person has symptoms that can be diagnosed, the cancer is already well developed and in many cases even metastatic.

This is a rare cancer, and one that is difficult to treat, so finding the best medical resources is crucial. A diagnosis may start with a patient’s general practitioner, but consultation with a specialist is necessary to get the best treatment. An online search can pull up mesothelioma specialists, but certain medical centers also provide great resources. Places like the M.D. Anderson Cancer Center in Houston and the Pacific Mesothelioma Center in Los Angeles are home to experts in the treatment of this disease.

Legal and Financial Resources
Many people who developed mesothelioma did so because they were exposed to asbestos in the workplace without knowing they were being put at risk. This means that many employers, including the U.S. military, as well as manufacturers of asbestos materials, can be blamed and sued for mesothelioma diagnoses.

A legal team that specializes in mesothelioma and asbestos can be a great legal resource to help patients decide if they have a case to make and then to file lawsuits that will win them settlements. In addition to lawsuits, mesothelioma patients may have access to asbestos trust funds, funds set up by companies to pay for future cases of mesothelioma in their past employees.

Resources for Veterans
Veterans of the U.S. military, especially those from the Navy, may have suffered more asbestos exposure than any other group of people. Through the U.S. Department of Veterans Affairs (VA), these mesothelioma patients can find specialized resources. Veterans can apply for VA compensation for asbestos exposure and must meet certain requirements. These include being exposed to asbestos during military service and being diagnosed with mesothelioma or another illness caused by that exposure.

How Mesothelioma.net Can Help
There are many resources for patients with mesothelioma, and it can get confusing. Mesothelioma.net offers one consolidated resource with information about medical treatments, financial assistance, asbestos trust funds, resources for veterans, and more. When you contact our site, we will send free information and can help connect you to legal experts, patient advocates, and other experts who will get you the help you need.

Monday, September 4, 2017

For Italians with Disabilities, a Place in the Sun



This morning I was sitting in the sun with my beagle on one side and spitz on the other. Both wanted equal time with my attention. The temperature was 65 degrees with low humidity and not a cloud in the sky. Life can’t get much better than this.

When I returned to my office, I saw this New York Times article by Elisabetta Povoledo on Italian beaches. You can read the entire article by clicking on the title below.

It reminded me of why we quit going to the beach. We found most beaches not accessible to the handicapped. Just getting down to the beach can be a problem. Once you are there, you still need a way to navigate across the sand. Fortunately, I now understand some beaches are more accessible and equipment rentals are available. Yet, most beaches still do not have adequate facilities for those of us with progressive disorders that cannot be easily transferred.

ForItalians with Disabilities, a Place in the Sun


“FOCENE, Italy — On a recent summer morning, one lido on the beach at Focene, west of Rome, was bustling. Italians of all ages and sizes sizzled on sun-bleached chairs. Children splashed happily among the waves, and a group of senior citizens exercised (gently) to a mambo beat.

But there were also visitors rarely seen on other Italian beaches: people with disabilities being eased into the water on special chairs with fat tires, with the help of family members and volunteers.

This summer, like all summers, Italians thronged the thousands of resorts and lidos that pepper the country’s coastline, staking out swatches of sand among colorful umbrellas arranged in cramped rows.

It’s a time-honored national pastime enjoyed by millions. But the seaside establishments that accommodate people in wheelchairs are few and far between….”

Saturday, September 2, 2017

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.

Thursday, August 31, 2017

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).

Sunday, August 20, 2017

Airway Obstruction after Robot-Assisted Laparoscopic Prostatectomy

This PubMed article was forwarded to me from another man with Kennedy's Disease. Read the entire article by following the title link.

It once again reiterates the need for extra caution when preparing for surgery. Discussions with the surgeon and the anesthesiologist are warranted.


Previously Undiagnosed Spinal and Bulbar Muscular Atrophy as a Cause of Airway Obstruction after Robot-Assisted Laparoscopic Prostatectomy

"... CONCLUSIONS: Vocal cord paralysis combined with postoperative laryngeal edema, the cause of which was presumed to be SBMA, likely caused airway obstruction after RALP. As neuromuscular symptoms progress gradually in patients with SBMA, muscle relaxants should be used carefully, even if patients with SBMA present no immobility of their extremities."

Tuesday, August 15, 2017

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



Friday, August 11, 2017

Muscle Tissue Changes with Aging


I caught a comment last night while watching TV that was interesting. The body loses an average of 5% of its muscle tissue with each decade after 30. It made me realize the double jeopardy those of us living with a progressive muscular disorder face.

I turned 70 this year. Over the last several years, I noticed my muscle mass appeared to decline more rapidly. Initially, I concluded this was more a perception and not reality. After reading this study, I now believe it is true. Interesting.

Today I did a little research and came across the following NIH study. Follow the link in the title to read the entire article.
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“Purpose of review

This review article focuses on the changes that occur in muscle with age, specifically the involuntary loss of muscle mass, strength and function, termed sarcopenia. Particular emphasis is given to the metabolic alterations that characterize sarcopenia, and to the potentially treatable causes of this condition, including age-related endocrine and nutritional changes, and inactivity.

Introduction

One of the most striking effects of age is the involuntary loss of muscle mass, strength, and function, termed sarcopenia. Muscle mass decreases approximately 3–8% per decade after the age of 30 and this rate of decline is even higher after the age of 60. This involuntary loss of muscle mass, strength, and function is a fundamental cause of and contributor to disability in older people. This is because sarcopenia increases the risks of falls and vulnerability to injury and, consequently, can lead to functional dependence and disability. A decrease in muscle mass is also accompanied by a progressive increase in fat mass and consequently changes in body composition, and is associated with an increased incidence of insulin resistance in the elderly. Furthermore, bone density decreases, joint stiffness increases, and there is a small reduction in stature (kyphosis). All these changes have probable implications for several conditions, including type 2 diabetes, obesity, heart disease, and osteoporosis.

Recent findings
Recent data reported include those regarding the potential role of insulin resistance in the development of sarcopenia, the potential role of androgens and growth hormone in the treatment of this condition, the usefulness of exercise including both resistance and aerobic training to improve muscle growth and function, and, finally, the possible use of nutritional manipulations to improve muscle mass.

Summary

Sarcopenia is likely a multifactorial condition that impairs physical function and predisposes to disability. It may be prevented or treated with lifestyle interventions and pharmacological treatment. Further long-term investigations are needed, however, to ascertain what type and combinations of interventions are the most efficacious in improving muscle mass and function in older people. …”

Image:  myheart.net

Thursday, August 10, 2017

CRISPR - Gene Editing Explained

A man living with Kennedy's Disease posted this on Facebook. The short YouTube video (link below) does a good job of explaining what CRISPR is, how it works, and its potential. Those of us living with KD are very interested in the potential tools like CRISPR offer for future generations.




Video published May 24, 2017

CRISPR is a new area of biomedical science that enables gene editing and could be the key to eventually curing diseases like autism or cancer. WIRED has challenged biologist Neville Sanjana to explain this concept to 5 different people; a 7 year-old, a 14 year-old, a college student, a grad student and a CRISPR expert.

Saturday, August 5, 2017

Gene Editing Followup

A followup article in the New York Times by Pam Belluck dismisses some of the fears people have regarding Gene Editing. Since Huntington’s Disease is mentioned, that is a good sign for those of us with families living with Kennedy’s Disease. To read the entire article, follow the title link.


Gene Editing for ‘Designer Babies’? Highly Unlikely, Scientists Say

 “Now that science is a big step closer to being able to fiddle with the genes of a human embryo, is it time to panic? Could embryo editing spiral out of control, allowing parents to custom-order a baby with Lin-Manuel Miranda’s imagination or Usain Bolt’s speed?

News that an international team of scientists in Oregon had successfully modified the DNA of human embryos has renewed apprehensions that babies will one day be “designed.” But there are good reasons to think that these fears are closer to science fiction than they are to science.

Here is what the researchers did: repair a single gene mutation on a single gene, a defect known to cause — by its lonesome — a serious, sometimes fatal, heart disease. …”

“ … So are most physical diseases and psychiatric disorders. The genetic message is not carried in a 140-character tweet — it resembles a shelf full of books with chapters, subsections and footnotes.

So embryonic editing is unlikely to prevent most medical problems.

But about 10,000 medical conditions are linked to specific mutations, including Huntington’s disease, cancers caused by BRCA genes, Tay-Sachs disease, cystic fibrosis, sickle cell anemia, and some cases of early-onset Alzheimer’s. Repairing the responsible mutations in theory could eradicate these diseases from the so-called germline, the genetic material passed from one generation to the next. No future family members would inherit them.

But testing editing approaches on each mutation will require scientists to find the right genetic signpost, often an RNA molecule, to guide the gene-snipping tool.

In the study reported this week, it took 10 tries to find the right RNA, said Juan Carlos Izpisua Belmonte, a co-author and geneticist at the Salk Institute.

Dr. Greely noted that while scientists work to get human embryonic editing ready for clinical trials (currently illegal in the United States and many countries), alternate medical treatments for these diseases might be developed. They may be simpler and cheaper. …”

Thursday, August 3, 2017

The Last - I can only hope



A picture above my desk called, “The Last,” has a dual meaning for me. First off, I love the lithograph because it is so well done. To me it reflects the dying off of the American Indian culture. The second meaning is much more personal. I hope and pray I am the last male in my mother’s family with Kennedy’s Disease.

A NewYork Times article written by Pam Belluck reports on a recent study and potential milestone in genetic engineering. Nature,the International Weekly Journal of Science published the study this week. A portion of the article is shown below. Follow the links above to read the entire article and the study.

In Breakthrough, Scientists Edit a Dangerous Mutation From Genes in Human Embryos

“”Scientists for the first time have successfully edited genes in human embryos to repair a common and serious disease-causing mutation, producing apparently healthy embryos, according to a study published on Wednesday.

The research marks a major milestone and, while a long way from clinical use, it raises the prospect that gene editing may one day protect babies from a variety of hereditary conditions.

But the achievement is also an example of human genetic engineering, once feared and unthinkable, and is sure to renew ethical concerns that some might try to design babies with certain traits, like greater intelligence or athleticism.

Scientists have long feared the unforeseen medical consequences of making inherited changes to human DNA. The cultural implications may be just as disturbing: Some experts have warned that unregulated genetic engineering may lead to a new form of eugenics, in which people with means pay to have children with enhanced traits even as those with disabilities are devalued. …”

“… Scientists at Oregon Health and Science University, with colleagues in California, China and South Korea, reported that they repaired dozens of embryos, fixing a mutation that causes a common heart condition that can lead to sudden death later in life.

If embryos with the repaired mutation were allowed to develop into babies, they would not only be disease-free but also would not transmit the disease to descendants.

The researchers averted two important safety problems: They produced embryos in which all cells — not just some — were mutation-free, and they avoided creating unwanted extra mutations.

“It feels a bit like a ‘one small step for (hu)mans, one giant leap for (hu)mankind’ moment,” Jennifer Doudna, a biochemist who helped discover the gene-editing method used, called CRISPR-Cas9, said in an email. …”


"Desistance" is my current story I am in the final stages of editing. It is a Sci-Fi that takes place sixty years in the future. One of the storylines is the development of almost super-humans whose DNA has been edited to remove most of the known diseases. Perhaps it won’t be Sci-Fi after all.

Wednesday, July 19, 2017

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.

Wednesday, July 12, 2017

Autophagy - akin to a garbage disposal system

I thought I published an article on this study, but cannot find it. So, here it is.

Target Identified For Rare Inherited Neurological Disease

Scientists show bad androgen receptor impairs body’s ability to dispose of damaged cells

Researchers at University of California, San Diego School of Medicine have identified the mechanism by which a rare, inherited neurodegenerative disease causes often crippling muscle weakness in men, in addition to reduced fertility.

The study, published August 10 in the journal Nature Neuroscience, shows that a gene mutation long recognized as a key to the development of Kennedy’s disease impairs the body’s ability to degrade, remove and recycle clumps of “trash” proteins that may otherwise build up on neurons, progressively impairing their ability to control muscle contraction. This mechanism, called autophagy, is akin to a garbage disposal system and is the only way for the body to purge itself of non-working, misshapen trash proteins.

“We’ve known since the mid-1990s that Alzheimer's disease, Parkinson's disease and Huntington's disease are caused by the accumulation of misfolded proteins that should have been degraded, but cannot be turned over,” said senior author Albert La Spada, MD, PhD and professor of pediatrics, cellular and molecular medicine, and neurosciences. “The value of this study is that it identifies a target for halting the progression of protein build-up, not just in this rare disease, but in many other diseases that are associated with impaired autophagy pathway function.” ...

... “Our study tells us that if we can find a way to keep TFEB working, we likely can prevent this disease and others like it from progressing,” La Spada said. “We now have a target for new therapies to treat not only Kennedy's disease, but also many more common neurological disorders.”

Follow this link to read the entire article: UC San Diego News

Friday, July 7, 2017

Exercise! Are you kidding me?

If you are a frequent reader of my blog, you are aware of my feelings on the benefits of a regular exercise and stretching program. I exercise every day. I alternate between heavy (90+ minutes) and light days (30+ minutes). I exercise in the morning and in the evening. I don’t expect everyone to be as crazy as I am, but I do hope everyone will find a comfortable exercise routine that become part of your everyday routine.

Pulmonary and cardiac benefits, as well as joint lubrication and muscle memory, are the main reason I exercise. If I didn’t feel I was receiving any benefits from the routine, I wouldn’t do it.

Finding your own exercise program and routine is important. For that reason, I am including links to several articles on exercise and exercise programs. There are many more available on the internet, but these might be of benefit. As always, before starting any exercise program, discuss it with your doctor. And, if possible, have a physical therapist work with you initially to evaluate and recommend a program that fits your particular needs.


Monday, July 3, 2017

What Happened?



The Preamble of our Constitution states, "We the People of the United States, in Order to form a more perfect Union, establish Justice, insure domestic Tranquility, provide for the common defense, promote the general Welfare, and secure the Blessings of Liberty to ourselves and our Posterity, do ordain and establish this Constitution for the United States of America.

Tomorrow is Independence Day, Unfortunately, I have to ask what happened to our country? It appears Sir John Dalberg-Acton was right. “Power tends to corrupt, and absolute power corrupts absolutely.”

The United States is a "melting pot," a fusion of nationalities, cultures, and ethnicities - different elements "melting together" for the common good of all. 

I’m certain our foundering fathers couldn’t agree on everything. Each representative probably thought their way was the best for the country. Yet, they were able to set aside their differences and come together to create a nation. They knew the United States would not be perfect, nothing ever is. But, it would be far better than the alternatives.

They forged a nation that allows everyone 
  • to have an opinion
  • to practice their own beliefs
  • to disagree without fear of retaliation
These are our rights. 

Not everything has to be an “all-or-nothing” situation. Compromise shouldn’t be considered a weakness. Meeting somewhere in the middle allows for “Win-Win” situations for the common good of all.

I wish you a safe and happy 4th of July

Saturday, July 1, 2017

Happy Independence Day to our Canadian Brothers



From the History Website:

"On July 1, 1867, with passage of the British North America Act, the Dominion of Canada was officially established as a self-governing entity within the British Empire. Two years later, Canada acquired the vast possessions of the Hudson’s Bay Company, and within a decade the provinces of Manitoba and Prince Edward Island had joined the Canadian federation. In 1885, the Canadian Pacific Railway was completed, making mass settlement across the vast territory of Canada possible."

Monday, June 26, 2017

It is that time again ...

Health care is in the news and it is time to take action once again. The MDA Advocacy Group is asking for our help.

Health Care Reform

As health care reform debates continue in the Senate, MDA remains committed to advocating for principles of coverage set out in conjunction with leading national patient organizations that establish key elements necessary for adequate health care coverage.  The principles require that meaningful access to care be affordable, accessible, adequate and understandable.  In addition to these elements, maintaining a robust Medicaid program is essential to ensuring our community has access to the care it needs.  In May the U.S. House of Representatives passed its version of health care reform, and now that the U.S. Senate is working on its bill, we continue to work with the Senate and encourage all members of Congress to engage in a bipartisan effort to find solutions to the challenges with access to care and with maintaining the critical protections set out in the Medicaid program.  Thank you to all advocates who reached out to your members of Congress earlier this spring to advocate for the principles of coverage and Medicaid protections.  As the Senate considers its bill this week, we urge you to again ask your senators to keep the priciples of coverage in mind when moving their bill forward, and to highlight the importance of Medicaid coverage for the neuromuscular disease community.


Sunday, June 25, 2017

Congratulations Chris

I wrote about Chris Symonds sailing in the Para World Sailing Championships earlier this week. Chris lives with Kennedy's Disease, but that doesn't slow him down much.

Great news!
Chris won the Silver Medal. 
Below is a portion of the article from World Sailing announcing the medalists.


"Poland's Cichocki dominated the Men's Hansa 303 and three final day race wins handed him his second Para World Sailing title in as many years, having won gold in the SKUD18 at the 2016 Para World Sailing Championships.

Australia's Christopher Symonds fended off a late charge from Germany's Jens Kroker to seal silver. The German settled for bronze."

What a super accomplishment.

Thursday, June 22, 2017

If air travel is in your future, check this out ...



The MDA Advocacy group published the results of their survey on air travel. Below is the email the MDA sent out with a link to the full article. I have also included a link to the DOT’s annual report on disability-related complaints for air travel. It shows a 224% increase in complaints over the last ten years. That's huge, but when you consider the actual number of complaints it is staggering. 

2007 Report =13,766                               2016 Report = 30,830

And, we all know that a vast majority of problems experienced are never formally submitted to the DOT.

___________________

MDA Advocacy Newsletter

“In an effort to understand the scale and scope of challenges faced by the neuromuscular disease community when traveling by air, at the end of 2016 we surveyed the MDA community about their flying experiences. We received more than 2,000 responses, and we thank everyone who took the time to participate in the survey. We hope you'll take a moment to review the results to see how challenges with and access to air travel impact our community.

Over the past two years, MDA has made accessible air travel one of our policy priorities. We're working closely with policy makers, federal agencies, industry and other advocacy and disability rights organizations to help improve access to air travel for MDA families. For more information about traveling with limited mobility, visit MDA's Accessible Air Travel Resource Center.”

Click here to read the full article on the MDA website.

___________________

A few months ago, I called upon my readers to contact their representatives regarding this important issue. The bill introduced in the Senate recently would go a long way in helping this ongoing issue.

“While there are efforts in place to increase access to air travel, there is still much to be done to improve the rights of passengers with disabilities during air travel. Recently, the U.S. Senate introduced a bill that strengthens the rights of disabled passengers under the Air Carrier Access Act. Included in the bill are provisions to:

1. Strengthen enforcement to include specific protections of the rights of passengers with disabilities and recourse when those rights are violated;

2. Ensure airplanes are designed to accommodate people with disabilities and airlines meet accessibility standards, including safe and effective boarding and deplaning;

3. Provide better stowage options for assistive devices;

4. Improve access to seating accommodations;

5. Close service gaps in air travel for passengers with disabilities; and

6. Require that the U.S. Access board conduct a study to determine the ways in which individuals who use assistive devices can be accommodated through cabin wheelchair restraint systems.”

All of the above would help, but I especially like #6.

If interested, click here to access the annual DOT Reports on Disability-Related Air Travel Complaints.

Saturday, June 17, 2017

Chris Symonds to set sail against best in the world



The following article was written by Camron Slessor in The Advocate. We wish Chris smooth sailing and hope he brings home the cup.

-----------------------

Chris Symonds believes preparation will be key when he competes on the world stage later this month. 

The Wynyard Yacht Club member will travel from the North-West Coast to Germany to test his skills and compete against some of the best sailors in the world. 

The 2017 Para World Sailing Championships will be held in Kiel, Germany from June 21-26 with Symonds to be joined by coach and support Mike Darby on the trip abroad. 

Symonds has Kennedy’s Disease which is a progressive Motor Neuron condition effecting muscles throughout the body and currently there is no cure or treatment.

He will compete in the Hansa 303 male division at the event where there are 32 entrants from 26 different countries, he will be the only Australian representative in his division and this will be the first Para regatta he has attended.

Symonds said he was excited to compete on the international stage and the event was huge on the sailing calendar. 

“I’m very excited, it shows that you can compete on the world stage from Wynyard and the North-West of Tasmania, Wynyard is lucky to have so many skilled and supporting community members,” Symonds said. 

“For Para-sailing, yes it’s huge.

“Outside of the Paralympics, which only come about every four years, this regatta is so important for world sailing who have gone to huge lengths to attract entrants from 40 nations across the two fleets.”

Symonds said he wouldn’t have been able to make the trip later this month without the support of the community and his coach for the competition, Mike Darby. 

“Some emerging nations have free boat hire to get them there, realistically many people with disabilities are not so financial, so support is necessary for many.

“The support from Mike and many others is unbelievable. Considering I cannot even launch my yacht or lift myself out of it without support to do so. 

“I am sailing for the community, not myself.”

As he prepared to face the best competition in the world, Symonds said to battle against able bodied athletes would be great for him to test himself. 

“Preparation is the key. We have done all we can to be best prepared so whatever the result we should feel good about it,” he said. 

“Those with Kennedy’s Disease around the world are supporting and watching closely. 

“It shows that anything is possible even with this debilitating condition. 

“There are not any other sports that would allow me to compete equally with able bodied persons.” 

Darby will travel with Symonds as his coach and support for the trip with the pair long term rivals having sailed against each other for over 40 years.

Symonds said preparation and training had being full on for the pair since Easter with structured on water, off water, fitness, rules knowledge, boat and event preparation.

Symonds is the current Open Hansa 303 singles Tasmanian and Australian champion as well as the Asia Pacific and World Champion in the open category, meaning able bodied and mixed gender persons can compete

Friday, June 16, 2017

Another Robotic Suit

Well, actually, it is the latest version of a company’s exoskeleton.

I just read the article and saw the video on YahooNews. I went to the ReWalk website and learned more about it. It says that ReWalk is the first exoskeleton to receive FDA clearance for personal and rehabilitation use in the United States. Then I noticed that the Stair Function is currently not available in the United States.

It appears to be designed for spinal cord injuries. It also mentions rehab for stroke victims and people with Multiple sclerosis. Yet, in the FAQ Section, it mentions that people with ALS, Cerebral palsy, Traumatic brain injury, etc. can use it. So, it might be something for those of us living with Kennedy's Disease.

ReWalk has over eighty training centers in the United States and hundreds more throughout the world. I don’t know what it costs, but it appears some insurance companies and the V.A. are using it for rehab purposes.

It appears there are three different units. I grabbed this from the article. "The lightweight, small, wearable suit is much simpler than ReWalk’s device that enables paralyzed patients to stand, walk and navigate stairs. Unlike the ReWalk 6.0, which includes robotic leg attachments that can weigh nearly 50 pounds, the soft exoskeleton looks more like the harness construction workers wear for safety than a bionic system. It consists of a waist belt fitted with a motor and battery, flexible cables that transmit power from the motor to the ankles, leg braces and shoe sensors. And it’s all activated by the flick of a switch.

ReWalk has not yet determined how much the soft-exoskeleton suit will cost, but says it will be more affordable than the ReWalk 6.0, which has a list price of $77,000."

Who can use it?
Before using the device, confirm that the following prerequisites are met by the user:
  • Hands and shoulders can support crutches or a walker
  • Healthy bone density
  • Skeleton does not suffer from any fractures
  • Able to stand using a device such as EasyStand
  • In general good health
  • Height is between 160 cm and 190 cm (5′ 3″ – 6′ 2″)
  • Weight does not exceed 100 kg (220 lbs)
People with the following conditions should not use the ReWalk™:
  • History of severe neurological injuries other than SCI (MS, CP, ALS, TBI etc)
  • Severe concurrent medical diseases: infections, circulatory, heart or lung, pressure sores
  • Severe spasticity (Ashworth 4)
  • Unstable spine or unhealed limbs or pelvic fractures
  • Heterotopic ossification
  • Significant contractures
  • Psychiatric or cognitive situations that may interfere with proper operation of the device
  • Pregnancy

Monday, June 5, 2017

It’s Never Too Early or Too Late

If you are a regular reader, you know that I encourage staying active, mentally, socially and physically. Just because we have a life-changing condition, doesn't mean we have to sacrifice our life.

It is far too easy to allow the problems of the world, and with your health, to drag you down. I read an interesting article by Dr. Heather Snyder in The Costco Connection this weekend. She referenced “10 Ways to Love your Brain” from the Alzheimer’s website.


"Growing evidence indicates that people can reduce their risk of cognitive decline by adopting key lifestyle habits. When possible, combine these habits to achieve maximum benefit for the brain and body. Start now. It’s never too late or too early to incorporate healthy habits."
  1. Break a sweat. Engaging in regular physical activity. It elevates the heart rate and increases blood flow in the brain and body. We might not be able to do what we used to do, but we can still get a workout. I believe the key word here is ‘regular’.     
  2. Hit the books. Study in any stage of life will help reduce the risk of cognitive decline and dementia. Take a class; learn a foreign language, or a new instrument; or join a book club. Challenge your brain by trying something new/different.
  3. Butt out. Evidence shows that smoking increases risk of cognitive decline. Quitting smoking can reduce that risk to levels comparable to those who have not smoked.
  4. Follow your heart. Evidence shows that risk factors for cardiovascular disease and stroke — obesity, high blood pressure and diabetes — negatively impact your cognitive health. Take care of your heart and your brain just might follow.
  5. Heads up! Brain injury can raise your risk of cognitive decline and dementia. Wear a seat belt, use a helmet when playing contact sports or riding a bike, and take steps to prevent falls. I’ll repeat this last one … take steps to prevent falls.
  6. Fuel up right. Eat a healthy and balanced diet that is lower in fat and higher in vegetables and fruit to help reduce the risk of cognitive decline. Although research on diet and cognitive function is limited, certain diets, including Mediterranean and Mediterranean-DASH (Dietary Approaches to Stop Hypertension), may contribute to risk reduction.
  7. Catch some Zzz's. Not getting enough sleep due to conditions like insomnia or sleep apnea may result in problems with memory and thinking.
  8. Buddy up. Staying socially engaged may support brain health. Pursue social activities that are meaningful to you. Find ways to be part of your local community — or, just share activities with friends and family.
  9. Stump yourself. Challenge and activate your mind. Build a piece of furniture. Complete a jigsaw puzzle. Do something artistic. Play games, such as bridge, that make you think strategically. Challenging your mind may have short and long-term benefits for your brain.
  10. Take care of your mental health. Some studies link a history of depression with increased risk of cognitive decline, so seek medical treatment if you have symptoms of depression, anxiety or other mental health concerns. Also, try to manage stress.