Monday, December 11, 2017

Huntington’s breakthrough

I have mentioned in earlier articles that Huntington’s Disease share a common genetic defect. It was first reported several years ago a PubMed article links acommonality between HD, KD and SCA-1.

“…Three neurodegenerative diseases, Huntington's disease (HD), Kennedy's disease (hereditary spinobulbar muscular atrophy, SBMA), and type 1 spinocerebellar ataxia (SCA-1) have been found to share a common genetic defect: an unstable region of repeated CAG trinucleotides…”

This morning I read a BBC News report about a potential breakthrough in the treatment and possible cure of Huntington’s Disease. This appears to be another positive step forward in search of an eventual treatment or cure for Kennedy’s Disease.

Huntington’s breakthrough may stop disease

James Gallagher, Health and science correspondent, reports: “…The unstoppable death of brain cells in Huntington's leaves patients in permanent decline, affecting their movement, behaviour, memory and ability to think clearly.

  • Huntington's generally affects people in their prime - in their 30s and 40s
  • Patients die around 10 to 20 years after symptoms start
  • About 8,500 people in the UK have Huntington's and a further 25,000 will develop it when they are older Huntington's is caused by an error in a section of DNA called the huntingtin gene.
  • Normally this contains the instructions for making a protein, called huntingtin, which is vital for brain development. But a genetic error corrupts the protein and turns it into a killer of brain cells.


The treatment is designed to silence the gene…”


“…On the trial, 46 patients had the drug injected into the fluid that bathes the brain and spinal cord. The procedure was carried out at the Leonard Wolfson Experimental Neurology Centre at the National Hospital for Neurology and Neurosurgery in London. Doctors did not know what would happen. One fear was the injections could have caused fatal meningitis. But the first in-human trial showed the drug was safe, well tolerated by patients and crucially reduced the levels of huntingtin in the brain…”

Wednesday, December 6, 2017

Kennedy’s Disease and Botox - Possible Side Effects



A man with Kennedy’s Disease experienced increased phlegm in recent years causing coughing, gagging, and more difficulty talking. He saw a specialist to see if there was anything that could be done to help.

The gentleman contacted Dr. Christopher Grunseich at NIH to explain the situation and the procedure used to hopefully correct the issue.


“The last GI doctor recommended the possibility of reflux causing the problem and suggested an esophagus manometer test, followed by a pH sensor placed at the bottom of the esophagus to measure the pH for a 48 hour period. The results (attached) were negative as far as reflux but the lower esophagus sphincter muscle was too strong - indicating the possibility of saliva pooling at the lower esophagus and thus causing the problem. I was told that Botox placed around the lower esophagus muscle could cause it to relax and prevent the suspected pooling.”

He went on to explain the side effects of the injection. “…Within the last two weeks I have been noticing remarkable weakness in my upper body strength. My head drop has gotten worse and my left arm is twice as weak as it was before the procedure. Is there any way that the local injection could have spread throughout my entire body?”

Dr. Christopher Grunseich responded.


“Sorry to hear that you have been experiencing worsening weakness and head drop. It is possible that the botox has contributed to worsening some of your symptoms, although it is difficult to say this with certainty. There have been case reports of patients receiving botox who have had systemic side effects (weakness), and there are several individuals in the attached series who do not have an underlying neuromuscular condition with symptoms developing 6 weeks after injection. The chance of systemic side effects may be related to the total dose and frequency. Your dose was lower (100 Units) than others who have reported side effects (with doses usually closer to 700 Units), but the Kennedy’s Disease may also make your muscles more sensitive to a lower dose, if some of the botox did spread systemically.

The reasons why there may be systemic effects from Botox injection are not clear. I would recommend that you try some other intervention with the gastroenterologist regarding the lower esophageal sphincter muscle. Perhaps a pneumatic dilation would have the chance of fewer side effects. We would anticipate that the weakness symptoms would gradually improve if they are a side effect of the Botox. It would be good for the neurologist to also see you to evaluate the change in strength.”

Dr. Grunseich also a PDF report explaining the potential of increased weakness with the use of Botox. Click here to read that study. There is another also another study concerning endoscopic injections. Click here to read that study.

Tuesday, December 5, 2017

Advice from a 40-year veteran of Kennedy's Disease

Yes, sometimes I am amazed that it has been forty years in the making. I have learned a lot about living with Kennedy's Disease over these last four decades.



A young man stumbled upon my blog the other day and wrote me. He is 34 years old and just diagnosed with Kennedy's Disease. He wrote, "I don’t really know what to expect or even how to deal with things. Can you recommend to me anything as far as exercising or vitamin/ supplements or really anything I can do to try to remain my best possible. My neurologist will only see me every 6 months and really hasn’t told me much other then I need to see a genetic counselor  Any recommendations you may have will be appreciated  "

I responded:.

  • Exercise is important. Don't overdue, however. There is something called the 70% rule. Exercise to 70% of your capability. This will keep your good muscles and motor neurons strong and active without doing damage.

  • What your weight. As the condition progresses, it becomes more difficult to stay mobile. Keeping your weight down makes it easier to walk and sustain a good level of activity. 

  • Exercise and a good diet will go a long way in staying healthy. Inactivity and certain foods contribute to certain health conditions. Since we are less active, we don't burn as many calories and are more susceptible to certain conditions.

  • Safety first. When you are young, it shouldn't be too much of an issue, but I did a lot of damage in the early years because I didn't know when to back off.

  • Keep a positive mental attitude. 

  • Life doesn't end with KD; it just changes. If there is something positive about KD, it is the slow progression of the condition. You shouldn't observe too many problems in the early years. 

  • Seek out support from those of us living with KD. The KDA, the KDA Forum, Facebook, etc. Always remember you are not alone.

  • Most importantly, KD does not define who you are and what you are capable of doing. Observe, adjust and stay active. You might not physically be able to accomplish something the way you used to do it, but it can still be done or you can ask someone to do it for you.

What I thought of later:

  • Dr. Grunseich at the NIH recommended the following. Those of us living with Kennedy’s Disease should avoid high doses of B-6 because it worsens the neuropathy systems. The normal dosage in a multi-vitamin should be fine.

  • He also said that we should consider taking additional supplements of B-12 because it is good for the nervous system.

  • Swallow your pride. It is okay to ask for help when you need it. Others will understand and look forward to helping. 

  • The MDA Clinics are beneficial for those of us living with progressive conditions. There are clinics in most major cities in the U.S. and Canada. I am certain there are similar organizations in other countries. Join one of these groups. They provide excellent support and give you access to certain mobility aids through their "Loan Locker."

  • At some point when mobility has become an issue, consider taking Dutasteride. I feel it has helped me maintain my strength.

Wednesday, November 29, 2017

KDA Awards Five Research Grants



Five research grants were awarded totaling $199,000. Award recipients and summaries are listed below.

Award $50,000
Targeting AR toxicity in SBMA by modulation of USP7 activity.
Anna Pluciennik, Ph.D.
Department of Biochemistry and Molecular Biology
Thomas Jefferson University

Summary: PolyQ-expanded androgen receptor-dependent cellular toxicity in the neuromuscular system is a characteristic feature of SBMA pathogenesis, although the molecular mechanisms for these effects are poorly understood. However, because cellular toxicity in SBMA is likely to arise, at least in part, from the polyQ-expanded-dependent dysregulation of protein-protein interactions that sustain normal cellular function, we reasoned that identification of such dysregulated interactions might help reveal potential therapeutic targets for disease modification. Therefore, as part of a KDA-funded project (2014), we used a quantitative proteomics approach and identified a deubiquitinating enzyme, USP7, that preferentially interacts with polyQ-expanded AR and contributes to toxicity. In fact, we have demonstrated that not only does partial knockdown of USP7 protein expression decrease mutant AR-dependent aggregation and dihydrotestosterone-dependent cytotoxicity, but also that overexpression of the protein aggravates these cellular effects. These results establish the need for further investigation into the role of the deubiquitinating function of USP7 in SBMA pathogenesis. The objective of this -research is to investigate the functional consequence of pharmacological inhibition of USP7 deubiquitinase activity in cellular and mouse models of SBMA. These studies will extend our previous KDA-funded proteomics work and, if successful, will establish the validity of inhibition of USP7 activity as a therapeutic approach for the treatment of SBMA.


Award $50,000
Identification of New Polyglutamine-Specific Mutant AR-Interacting Proteins in SBMA Motor Neurons
Xia Feng
Postdoctoral Fellow, Neurogenetics Branch
National Institute of Neurological Disorders and Stroke, National Institute of Health

Summary: Spinal and bulbar muscular atrophy (SBMA) is a slowly progressive neuromuscular disease. As the disease proceeds, nerve cells in the spinal cord (called motor neurons) start to die and muscle cells will waste away. The causative mutation of SBMA is the mutant androgen receptor (AR) with an abnormal expansion in the certain region. Such aberrant expansion in the mutant protein (called a polyglutamine tract) damages the normal function of the protein as well as obtains toxicity. Thus, it is important to understand how the mutant AR is regulated via other proteins in the disease. Here, I propose to use a human induced pluripotent stem cell model to generate disease-relevant motor neuron-like cells, and use these cells to identify specific interacting proteins of the mutant androgen receptor. I am hoping that my research will help provide a motor neuron-specific basis for designing and developing novel therapeutics for the treatment of SBMA.


Award $33,000
Transcellular regulation of the proteostasis network in Kennedy’s disease
Laura Bott, Ph.D.
Postdoctoral Fellow
Molecular Biosciences, Northwestern University

Summary: Misfolding and abnormal accumulation of the mutant androgen receptor in Kennedy’s disease indicates that the cellular machinery controlling protein abundance, folding, and transport (proteostasis) may be defective in the disease. We are planning to study molecular mechanisms of Kennedy’s disease in the worm Caenorhabditis elegans. For this, we will genetically engineer worms to express the mutant androgen receptor in the neuromuscular system and assess effects of the polyglutamine expansion on proteostasis regulation in this model organism. Insights into cell type-specific effects and regulation across tissues may lead to new therapeutic approaches for this disease.


Award $33,000
One gene, many proteins: investigating the role of AR isoform 2 as a therapeutic target for SBMA
Carlo Rinaldi, MD, PhD
Department of Physiology, Anatomy and Genetics
University of Oxford

Summary: The activity of steroid hormone receptors, such as progesterone and oestrogen receptors, is modulated by a number of isoforms and splice variants in a tissue-specific manner, in both health and disease. Androgen receptor may be no exception. AR isoform 2, or AR45 by the molecular weight of its encoded widely-expressed protein, is the only naturally occurring AR isoform, arising from use of an alternative transcriptional start site in intron 1 of the AR gene and containing a short, unique seven amino-acid-long N-terminal stretch instead of the long N-terminal domain found in the full length AR. Overarching aim of this proposal is to unravel the contribution of AR isoform 2 to SBMA pathogenesis and provide a novel therapeutic target for this disease, suitable for oligonucleotide antisense targeting without running the risks associated with silencing of the only available copy of the AR gene in males.

Award $33,000
The use of induced stem cells and microfluidics for developing new assays to identify new therapies for Kennedy’s disease
Thomas M Durcan, Ph.D., Assistant Professor,
Montreal Neurological Institute, McGill University

Summary: It is important to explore new avenues in the search for treatments for Kennedy’s disease (KD). Our overall goal is to develop disease-relevant assays that use human motor neurons made from stem cells of both men with Kennedy’s disease and healthy individuals. Using special silicone microfluidic devices to grow motor neurons, we will measure the function of neurons upon exposure to different compounds. First, we will develop assays to measure the survival and growth of the motor neurons. Next, we will look at the how well mitochondria work and move within the neurons. Finally, we aim to set up an assay to test the ability of the normal and KD motor neurons to form synapses (junctions). Taken together, these innovative assays will provide a foundation to build a KD drug discovery platform to screen for promising compounds and targets to treat KD.

Monday, November 27, 2017

Is ASO a potential treatment for Kennedy’s Disease?

This is a follow up to my November 15, 2017, article, “MDAAnnounces SBMA Research Grant.” The research paper was a little over my head (nothing new for me), so I asked the KDA’s resident biology professor, Ed Meyertholen, to explain what Dr. Lieberman’s research was about. Below is Ed’s summary of the grant. For a short primer, I have included the link to a video on DNA-RNA.


"The grant the Andy Lieberman received was to continue the research on the use of Anti-Sense Oligonucleotides (ASO) as a treatment for Kennedy’s Disease (KD). To best understand how it works, it is important to remember the following:

1. KD is believed to be the result of a misfolded protein, specifically, the protein known as the Androgen Receptor (AR).

2. Proteins are built of specific sequences of amino acids, thus to make a protein, one must have amino acids and the sequence of the amino acids of the protein of interest.

3. The sequence of amino acids for any protein are hard coded into our genes - our DNA.  Thus to make a particular protein, the cell must find the gene that codes for the sequence for that protein and read the code to get the sequence.  The structure of the cell that makes the protein is the ribosome.

4. In KD, the misfolded protein is known as the Androgen Receptor (AR) and it misfolds because our DNA has an error in the sequence.  So, when our cells want to synthesize the AR, our instructions are faulty and when we make the resulting protein, it somehow causes cells to die albeit, slowly.

5. Protein synthesis requires two major steps, the first is the synthesis of an RNA copy (RNA is like DNA) of the gene (DNA) which codes for the protein of interest (this occurs in the nucleus).  The RNA synthesis is known as transcription.

6. The RNA copy (which contains the code for the protein) leaves the nucleus and goes to the ribosome.  Here the code is read and the protein is synthesized.  This actual making of the protein is known as translation.

7.  An ASO is a specially designed fragment of RNA that binds only to a specific RNA.  An ASO can be designed to bind specifically to any given RNA.  In this case, the ASO binds only to the RNA that is used to make the AR.  When the ASO binds to the RNA, the cell responds by destroying the RNA (that is what it does) - thus the RNA to make the AR is destroyed before the protein is made and thus no AR is synthesized and thus, it is hoped, no KD.

8.  Andy's grant is, as I understand it, will try to test this procedure on mice models of KD and involve investigating the best ways to deliver the ASO.  Let me also add, there have been several published studies that have shown that ASO's are effective in preventing KD in mice.  Other ASO's have been developed to treat other diseases and just recently, one was approved for use in a disease called Spinal Muscular Atrophy (this is not KD)."  

Friday, November 17, 2017

Nonalcoholic fatty liver disease in spinal and bulbar muscular atrophy


Nonalcoholic fatty liver disease in spinal and bulbar muscular atrophy


Robert D. Guber, BS*, Varun Takyar, MD*, Angela Kokkinis, BSN, RN, Derrick A. Fox, MD, Hawwa Alao, MD, Ilona Kats, BA, Dara Bakar, BA, Alan T. Remaley, MD, PhD, Stephen M. Hewitt, MD, PhD, David E. Kleiner, MD, PhD, Chia-Ying Liu, PhD, Colleen Hadigan, MD, Kenneth H. Fischbeck, MD, Yaron Rotman, MD and Christopher Grunseich, MD
Correspondence to Dr. Grunseich: christopher.grunseich{at}nih.gov

ABSTRACT

Objective: To determine the prevalence and features of fatty liver disease in spinal and bulbar muscular atrophy (SBMA).

Methods: Two groups of participants with SBMA were evaluated. In the first group, 22 participants with SBMA underwent laboratory analysis and liver imaging. In the second group, 14 participants with SBMA were compared to 13 female carriers and 23 controls. Liver biopsies were done in 4 participants with SBMA.

Results: Evidence of fatty liver disease was detected by magnetic resonance spectroscopy in all participants with SBMA in the first group, with an average dome intrahepatic triacylglycerol of 27% (range 6%–66%, ref ≤5.5%). Liver dome magnetic resonance spectroscopy measurements were significantly increased in participants with SBMA in the second group relative to age- and sex-matched controls, with average disease and male control measurements of 17% and 3%, respectively. Liver biopsies were consistent with simple steatosis in 2 participants and nonalcoholic steatohepatitis in 2 others.

Conclusions: We observed evidence of nonalcoholic liver disease in nearly all of the participants with SBMA evaluated. These observations expand the phenotypic spectrum of the disease and provide a potential biomarker that can be monitored in future studies.

Photo:  https://www.quora.com/What-is-liver-failure

Thursday, November 16, 2017

US scientists try 1st gene editing in the body

In recent years I have reported several times about CRISPR and gene editing. I am not a scientist, but, to a layman, this sounds like the best possibility for curing Kennedy's Disease. In the article referenced below, it discusses the potential benefits and possible dangers of gene editing.

There is much more research that needs to be done, but the possibility of a cure is now closer than ever before.

US scientists try 1st gene editing in the body


"...This time, the gene tinkering is happening in a precise way inside the body. It’s like sending a mini surgeon along to place the new gene in exactly the right location.

“We cut your DNA, open it up, insert a gene, stitch it back up. Invisible mending,” said Dr. Sandy Macrae, president of Sangamo Therapeutics, the California company testing this for two metabolic diseases and hemophilia. “It becomes part of your DNA and is there for the rest of your life.”

That also means there’s no going back, no way to erase any mistakes the editing might cause.

“You’re really toying with Mother Nature” and the risks can’t be fully known, but the studies should move forward because these are incurable diseases, said one independent expert, Dr. Eric Topol of the Scripps Translational Science Institute in San Diego.

Protections are in place to help ensure safety, and animal tests were very encouraging, said Dr. Howard Kaufman, a Boston scientist on the National Institutes of Health panel that approved the studies.

He said gene editing’s promise is too great to ignore. “So far there’s been no evidence that this is going to be dangerous,” he said. “Now is not the time to get scared.”..."

A short APNews animation video does a good job of explaining the process. 

(AP Animation/Marshall Ritzel)

Wednesday, November 15, 2017

MDA Announces SBMA Research Grant

This week the MDA announced the awarding of more research grants. Of particular interest to those of us living with Kennedy’s Disease (SBMA) is the following grant.

Testing a potential therapy for spinal-bulbarmuscular atrophy (SBMA)

“Scientists at the University of Michigan Medical School in Ann Arbor are completing preclinical studies in a mouse model to establish the safety and efficacy of a new type of therapy to silence activity of the gene that is mutated in SBMA.”

Below is the abstract of the research noted in the above announcement. It should be noted that Dr. Lieberman serves on the Kennedy’s Disease Association’s Scientific Review Board.

Rescue of MetabolicAlterations in AR113Q Skeletal Muscle by Peripheral Androgen Receptor GeneSilencing

Giorgetti E1, Yu Z1, Chua JP1, Shimamura R1, Zhao L2, Zhu F3, Venneti S1, Pennuto M4, Guan Y3, Hung G5, Lieberman AP6.
Abstract

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

Friday, November 10, 2017

Life Doesn’t End With The Diagnosis


I remember when I was diagnosed with ALS. I could not have been more devastated. Then, a few years later, when my diagnosis was corrected to Spinal Bulbar Muscular Atrophy, it was initially a relief. It did not take long, however, for reality to settle in. I had Kennedy’s Disease!

My symptoms appeared in the late 20s. I am now 70. When I look back at those first days after finding out I had KD, I have to laugh. Life did not end with the diagnosis. It began.

After the initial shock, I realized I had control of my thoughts and feelings. The diagnosis was also a wake-up call. I climbed mountains in my 40s, sailed the San Juan Islands, explored the reefs in Hawaii, hiked hundreds of miles of trails in the mountains and lowlands, and became a licensed pilot. I could go on, but all this happened after the symptoms appeared.

The redeeming feature of Kennedy’s Disease is it progresses slowly. I still have good days and bad days, just as I did before KD. I still become frustrated and resentful at times. I still lash out at others when it is meant for me. And, what is interesting about this is that these events would also happen if I did not have KD. It is called ‘LIFE’. I experience, adjust and adapt. But, I continue to live the best life possible.

Life is a journey of discovery. And, as with any person’s life, there are hills and valleys, as well as rivers and deserts, that have to be traversed. There will be good times and not so good times, but each will be its own learning experience. That is why this blog is called, “Living with Kennedy’s Disease… until there is a cure.


Photo: https://weheartit.com/entry/42876870

Monday, November 6, 2017

Mouth and tongue fasciculations in Kennedy’s disease



SpringLink has a video of fasciculations of the tongue and mouth.

“…Abstract - We report the case of a 54-year-old right-handed man who presented with a 2-year history of progressive upper-limb weakness with mild dysarthria and prominent involuntary perioral abnormal movements that were characterized as fasciculations…”


For those who have never experienced fasciculations, it is the strangest sensation and it is uncontrollable. The ones running up and down my back, for example, feel like I have an alien in my body trying to escape. They use to bother me. Since I have lived with them for over half of my life, I now consider them a part of the family. J

Friday, November 3, 2017

Gene Replacement Therapy for Spinal Muscular Atrophy Type 1

Even though this is not Kennedy’s Disease (SBMA) related, the gene replacement therapy mentioned in the two articles shows another major step forward in this type of treatment. If they can accomplish these type results for SMA1, the potential treatment for Spinal Bulbar Muscular Atrophy is a little closer.

The Gene Therapy Animation is short, but nicely explained in this YouTube video


Note: Information for parents of children with SMA1 who want to learn more about study participation can visit: studysmanow.com.

The well-written article explaining Dr. Mendell’s research in Nationwide Children’s does a good job of explaining the treatment and where they are in the process.

Phase 1 Replacement Therapy Article


“…SMA1 is a progressive, childhood, neuromuscular disease caused by a mutation in a single gene. Children with SMA1 fail to meet motor milestones and typically die or require permanent mechanical ventilation by 2 years of age. The phase 1 clinical trial is the first to test the functional replacement of the mutated gene responsible for SMA1.

A one-time intravenous injection of modified adeno-associated virus serotype 9 (AAV9) delivered the SMN gene to 15 patients. Three patients received a low dose, while 12 patients received a high dose. In the Phase 1 trial, patients in the high dose group demonstrated improvement in motor function and they had a decreased need for supportive care compared to the natural history of the disease.

Specifically, at the end of the study period, all 15 patients appeared to have a favorable safety profile and to be generally well tolerated. Of the 12 patients treated with the high dose, 92 percent of patients have achieved head control, 75 percent of patients can roll over and 92 percent of patients can sit with assistance. Seventy-five percent of these patients are now sitting for 30 seconds or longer. Two patients can crawl, pull to stand and stand and walk independently.


According to natural history of the disease, patients require nutritional and respiratory support by 12 months of age, and are not able to swallow or speak effectively. Of the patients who received the high dose in study, 11 patients are able to speak, 11 patients are fed orally and seven do not require bi-level positive airway pressure as of the data cut-off (August 7, 2017)…”

Thursday, October 26, 2017

When Should I Tell My Employer About My Condition?


One of the most difficult decisions I ever made was to advise my boss that I had Kennedy’s Disease. Pride, fear and the other unknowns kept me from disclosing my condition for far too long. Yet, after I told him, I discovered he was understanding and supportive of my condition and situation. Several accommodations were made that allowed me to work safely productively for several more years.

I don’t believe there is ever the “right time” to have the discussion because there are too many unknowns. But, when you begin to see possible job performance or safety issues involved, it is probably time to step up. As the article states, disclosing your condition is a matter of personal choice.

The MDA’s QuestMagazine has an article written by Karen Henry about disclosing your disability to your employer. A portion of the article is shown below. To read the entire article, click on the MDA Quest link above.

“…Talking with employers about neuromuscular disease can be challenging. Given the broad spectrum of neuromuscular diseases and their often unpredictable nature, some may find it difficult to navigate exactly when and how much to disclose. 

“The very first thing a person needs to consider is why you want to disclose,” says Sharon Rennert, senior attorney advisor at the U.S. Equal Employment Opportunity Commission (EEOC). Doing so for the right reason at the right time keeps the focus on your performance as an employee, rather than on your disability…”

“…Ultimately, disclosing information about your disability to your employer is a personal choice. Choosing not to disclose your disability might be the most appropriate choice if you are able to perform all your essential job functions without extra assistance. However, if your disability begins to impact your job performance, you could be held accountable for performance issues if you have not disclosed your disability and asked for reasonable accommodations.

“Even if you’re not quite sure what accommodations might help you, it is better to get the ball rolling,” Rennert says. “The last thing anybody wants is for there to be disciplinary action based on poor performance.”

Miller agrees. “It’s OK to let people around you know what you’re going through. It’s OK to take accommodations that are necessary for your disability…”

“…Title I of the Americans with Disabilities Act (ADA) of 1990 prohibits private employers, state and local governments, employment agencies and labor unions from discriminating against qualified employees with disabilities. They also must make reasonable accommodations employees with disabilities need to perform their jobs.


According to the U.S. Equal Employment Opportunity Commission (EEOC), a reasonable accommodation is any change in the workplace or the way things are customarily done that provides an equal employment opportunity to an individual with a disability. “The types of accommodations an employer could provide are quite broad,” says Sharon Rennert, senior attorney advisor at the EEOC…”

Sunday, October 22, 2017

Caregivers are People Too

The role of caregiver is often a thankless and often never-ending job. Fear, frustration, guilt, exhaustion, and burnout are often associated with long-term caregivers. Besides providing care, the caregiver is always thinking of ways to help make life easier for those in their care.

Caregivers also have another responsibility that is often lost in their daily duties. They also need to take care of his or herself including finding some “alone time” to recharge the batteries.

Far too often, the caregiver’s needs are forgotten. With the advent of cell phones and alert bracelets, being on-duty 24-7 doesn’t have to mean giving up their personal lives. And, even though we might say “Thanks” and “Provide Encouragement”, it is not enough. We need to find ways to be a caregiver to our caregiver. It can mean something as simple as giving the caregiver some “guilt free” time away from their duties. Or, it can mean encouraging the caregiver to go to a spa or the gym for a few hours—or, maybe taking in a movie or dinner with friends. Hobbies are also a wonderful distraction. 

The following are some tips from an article from the Family Caregivers Alliance. To read the entire article, click on this link.

TakingCare of YOU: Self-Care for Family Caregivers.


Summing Up

Remember, it is not selfish to focus on your own needs and desires when you are a caregiver—itʼs an important part of the job. You are responsible for your own self-care.


Reducing Personal Stress

How we perceive and respond to an event is a significant factor in how we adjust and cope with it. The stress you feel is not only the result of your caregiving situation but also the result of your perception of it—whether you see the glass as half-full or half-empty. It is important to remember that you are not alone in your experiences.


Setting Goals

Setting goals or deciding what you would like to accomplish in the next three to six months is an important tool for taking care of yourself.


Seeking Solutions

Seeking solutions to difficult situations is, of course, one of the most important tools in caregiving. Once youʼve identified a problem, taking action to solve it can change the situation and also change your attitude to a more positive one, giving you more confidence in your abilities.


Communicating Constructively

Being able to communicate constructively is one of a caregiverʼs most important tools. When you communicate in ways that are clear, assertive, and constructive, you will be heard and get the help and support you need.


Asking for and Accepting Help

When people have asked if they can be of help to you, how often have you replied, “Thank you, but I'm fine.” Many caregivers donʼt know how to marshal the goodwill of others and are reluctant to ask for help. You may not wish to “burden” others or admit that you can't handle everything yourself.

Be prepared with a mental list of ways that others could help you. For example, someone could take the person you care for on a 15-minute walk a couple of times a week. Your neighbor could pick up a few things for you at the grocery store. A relative could fill out some insurance papers. When you break down the jobs into very simple tasks, it is easier for people to help. And they do want to help. It is up to you to tell them how.

Help can come from community resources, family, friends, and professionals. Ask them. Donʼt wait until you are overwhelmed and exhausted or your health fails. Reaching out for help when you need it is a sign of personal strength.


Talking to the Physician

In addition to taking on the household chores, shopping, transportation, and personal care, 37 percent of caregivers also administer medications, injections, and medical treatment to the person for whom they care. Some 77 percent of those caregivers report the need to ask for advice about the medications and medical treatments. The person they usually turn to is their physician.

But while caregivers will discuss their loved oneʼs care with the physician, caregivers seldom talk about their own health, which is equally important. Building a partnership with a physician that addresses the health needs of the care recipient and the caregiver is crucial. The responsibility of this partnership ideally is shared between you, the caregiver, the physician, and other healthcare staff. However, it will often fall to you to be assertive, using good communication skills, to ensure that everyoneʼs needs are met—including your own.


Starting to Exercise

You may be reluctant to start exercising, even though youʼve heard itʼs one of the healthiest things you can do. Perhaps you think that physical exercise might harm you, or that it is only for people who are young and able to do things like jogging. Fortunately, research suggests that you can maintain or at least partly restore endurance, balance, strength, and flexibility through everyday physical activities like walking and gardening. Even household chores can improve your health. The key is to increase your physical activity by exercising and using your own muscle power.

Exercise promotes better sleep, reduces tension and depression, and increases energy and alertness. If finding time for exercise is a problem, incorporate it into your daily activity. Perhaps the care recipient can walk or do stretching exercise with you. If necessary, do frequent short exercises instead of those that require large blocks of time. Find activities you enjoy.

Walking, one of the best and easiest exercises, is a great way to get started. Besides its physical benefits, walking helps to reduce psychological tension. Walking 20 minutes a day, three times a week, is very beneficial. If you canʼt get away for that long, try to walk for as long as you can on however many days you can. Work walking into your life. Walk around the mall, to the store, or a nearby park. Walk around the block with a friend.


Learning from Our Emotions


It is a strength to recognize when your emotions are controlling you (instead of you controlling your emotions). Our emotions are messages to which we need to listen. They exist for a reason. However negative or painful, our feelings are useful tools for understanding what is happening to us. Even feelings such as guilt, anger, and resentment contain important messages. Learn from them, then take appropriate action.

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).