Embarrassing Moments – Part I

All of us with Kennedy's Disease have to learn to live with embarrassments. Some are major, while others are minor. And, even though they were embarrassing at the moment, they also leave us with fond memories and an occasional laugh for years afterwards.

This will be my first post on the subject of embarrassments in my life. This happened several years ago, but is still fresh in my mind. At the time, I had not told anyone at work that I had this health issue.

Background: Men with Kennedy's Disease learn early on that the motor neurons do not always function in synchrony. Sometimes muscles will receive signals hours or even days later. This is what causes the twitches and spasms in the muscle groups. Because of these delayed signals, you might receive a muscle response when you do not want it. My case in point …

Customer Appreciation Dinner – Our top customers were in town for a marketing seminar and dinner party. We were all standing around before dinner having cocktails. I was wandering between customers and carrying on polite conversations. At the time, I was talking with two of our customers while holding a Club Soda in my left hand so my right hand was free to shake hands (I am a non-drinker much to the disrespect of my older brother). While discussing the golf outing scheduled for the next day, my left wrist received a delayed signal. Without warning, the wrist just turned inwards as if I was taking a drink. My glass turned over dumping the contents on my shoes.

The two customers just stared at my shoes without saying anything. I was just as shocked as they were. Needless to say, I turned a little red. I then recovered, smiled, and as I bent down to wipe off my shoes, I commented, "I think it is time I switch to water for the rest of the evening." We all had a good laugh, but I never forgot the moment. Fortunately, the only thing hurt was my pride (and it bruises easy).

The Top Five Questions Asked

I am often asked questions about Spinal Bulbar Muscular Atrophy (better known as Kennedy's Disease). I would easily say that 90% of the questions asked could be summarized in the following Q&A.



Q: Who gets Kennedy's Disease?

A: Kennedy's Disease is a genetic disease, passed on from generation to generation in a family.  It is an X-linked recessive inherited gene.  Generally, males who inherit the gene exhibit symptoms, while females who inherit the gene are usually just carriers.  Females, in some instances, may also exhibit symptoms (especially in their later years).

Q: How is Spinal Bulbar Muscular Atrophy (Kennedy's Disease) diagnosed?

A: Up until the mid-1990s, Kennedy's Disease was often misdiagnosed. Fortunately, there is a blood test today that checks a person's DNA for the defective chromosome. Any doctor or nurse can draw the blood and send it off to a DNA laboratory for testing. Test results are normally returned within three-to-six weeks. The test determines the number of CAG repeats within the Androgen Receptor (AR) gene.

• If you have less than34 repeats, that is considered normal
  
• If you have 34-39 repeats, you are considered "borderline" and you could experience some minor symptoms
  
• Repeats that are 40 or greater reflect that you have the full gene mutation (abnormal expansion of the CAG tandem repeat)
  

Since females have two X-chromosomes, they can have either one, and in rare cases both, chromosomes defective.

Q: Can the disease be passed on to my children?

A: If the mother is the only carrier of the defective gene (in the X-chromosome), there is a 50 % chance of passing the affected gene on to male children (in which case, they would develop symptoms in adulthood). The chance of passing the defective gene on to female children is also 50% (in which case, they would be carriers of the gene, but probably never develop the actual symptoms). If the father is the only carrier of the defective gene, the chances of passing the defective gene to a male child are 0%. However, it is 100 % certain that the gene will be passed on to a female child, and she will be a carrier of the gene. This Genetic Chart shows the possible ways the gene can be passed. 

Q: One of my parents has the defective gene. I have or am considering having children. Should I be tested or should I have my children tested?

A: Some families have even considered prenatal testing. If you have this concern, you should consult with a genetic counselor. These professionals are best equipped to help answer these type questions.

Q: Why don't we hear much about Kennedy's Disease?

A: Kennedy's Disease is considered a rare medical disorder. It is estimated that only 1 in 40,000 individuals worldwide have Kennedy's Disease. However, since many go misdiagnosed or undiagnosed for years, it is difficult to quantify how many have this gene defect. Normally, when a person is diagnosed with the defective gene, they usually comment that they have a brother, uncle, or grandfather that had similar symptoms.

Glimmers of Hope – Part IV

Profiles of Young Researchers

In an earlier post called, "The Nine Stages," I mentioned "Hope" was the ninth stage. I ended the post by saying, "With acceptance, and armed with the additional knowledge that researchers were working diligently towards finding a treatment and potentially a cure, I discovered something that had been missing recently in my life – Hope."

In my post, "Another Ray of Hope on the Research Front," I commented, "how fortunate we are that another generation has picked up the baton and continues to move towards the finish line (finding a treatment or cure). As long as someone is carrying the baton, we have hope."

In this post, I wish to recognize another researcher who is carrying the baton:

Tobias Jochum, Post Grad Student, is a researcher at the Institute for Synchroton Radiation, Forgschungszentrum Karlsruhe, in Eggenstein-Leopoldshafen, Germany.

Bruce: Why did you decide to focus your research on Kennedy's Disease?

Tobias: After my diploma thesis, which was more related to different biophysical techniques, I decided to move on with a more biological topic for my PhD. However, I wanted to use the knowledge that I had acquired during my studies for the prospective PhD project. Together with my diploma supervisor Dr. David Moss and Prof. Andrew C. Cato we discussed in a few meetings how research on SBMA (Kennedy's Disease) and modern biophysical methods could be combined in order to contribute to this research field. I decided then to study the current literature and found out that SBMA (Kennedy's Disease) and the related polyQ diseases are open research areas- this made me curious.

Bruce: Briefly summarize what you are currently working on and why you feel it is important in KD research.

Tobias: My research on SBMA has the objective to use recent technological advancements in biophysical methods to characterize the protein aggregation process in (Kennedy's Disease) which is caused by the polyglutamine-extended sequences in the androgen receptor. This, we believe, will provide a deeper understanding of the molecular processes associated with SBMA (Kennedy's Disease). It will also provide a robust assay that could be used to predict the efficacy of future chemical compounds for the treatment of SBMA (Kennedy's Disease).

Bruce: What are your aspirations (career goals)?

Tobias: First of all, I want to finish my PhD. Afterwards I will try to find a post-doc position that should definitely be related to neurodegeneration and studies using biophysical methods.

Why did I name this blog “Living with Kennedy’s Disease?”

Recently I was asked why I chose "Living with Kennedy's Disease" as the title for my blog. After responding to the inquiry, I thought others might want to know also.

I feel the process of 'accepting' (living with and not fighting) Kennedy's Disease is not just something that happens. It is a learning process. Acceptance does not bring happiness or comfort. Instead, 'acceptance' means you are now able to acknowledge, understand, and deal with the reality of the situation. Life can once again begin to move forward.

The person with the defective gene is not the only one that has to learn to accept this health condition. The rest of the family is also intimately involved in this same learning process. Everyone in the family at some points needs to be able to say, "It's okay, I can live with this." Children will quickly sense your stress, fears and discomfort. They need to be able to discuss this health issue openly with you and understand how it might affect their lives. Often, especially when children are involved, a genetic counselor is helpful in explaining the symptoms and answering questions.

I believe that knowledge is power. Armed with the facts, it becomes easier to deflect initial concerns as well as logically assess current and future issues. Sharing that knowledge with the entire family (keeping topics relevant to the age of the children) is important especially as the disease progresses. By openly sharing this information, it helps release some of the fears and questions that the rest of the family might be harboring, but is afraid to voice.

Each person has to go through his or her own specific acceptance process (see The Nine Stages article). And, I do not believe that any two people go through the same exact process. Often, the most difficult part of this process is finding the information necessary (including finding a support group) to deal with all the questions that plaque each family member. Fear of the unknown is the most difficult situation to deal with.

The purpose of many of the posts in this blog is to provide you with information related to Kennedy's Disease to help you better understand and live with the disease. Other posts are my perceptions and life experiences that I hope you will find interesting, educational, and perhaps entertaining at times.

The above explanation is a roundabout way of telling you 'why'. If I shortened this post to one sentence, it would be, "I believe that part of my process of learning to live with (accept) Kennedy's Disease is to help others going down the same path."

The Never-Ending Learning Process

Feeling overwhelmed is something most of us with Kennedy's Disease have experienced. I have often said that the mental and emotional aspects of the disease are as difficult to handle as the physical ones. Frustration over not being able to perform a simple task is something that I still have not learned to live with. There is another aspect of living with the disease, however, and that is "the never-ending learning process."

What many of us have experienced through the years is that there are certain times that we can see a drastic reduction in strength for several weeks. I call it "the slide." Then, we hit a plateau where our strength just seems to level out for a period of time ... occasionally you might even feel slightly stronger. I always look forward to the plateaus because it allows me to stabilize my life around my new capabilities (if that makes sense).

Looking back upon some of my experiences, I, at one time, exercised to excess. I thought that if I felt weaker, than all I need to do was exercise more often and push myself harder. By doing this, I just knew I would somehow regain my strength. It did not work. I found that pushing myself beyond my capabilities caused more harm than good. The muscles need to rest after exercise.

As I matured (my acceptance and knowledge of the disease), my exercise program changed. The one I use today was developed by a physical therapist that is familiar with these type diseases. My program today is called "smart exercising." I still exercise every day (15-to-60 minutes depending upon the routine), but I alternate exercises to keep fresh and not over-tax any one muscle group. I have found the key to "smart exercising" is consistency and to listen to my body. I focus on muscle groups today and not individual muscles. Lightweight repetitions and stretching exercises are far better for me than weight building. I do not exercise until I am fatigued or hurting. If that happens, I have gone too far. And yes, most neurologists familiar with KD agree that exercise is good for you. It stimulates the motor neurons and keeps them firing. Healthy muscles remain strong and healthier longer.

While chewing and swallowing is second nature to most people, it is something else that requires my total focus. As my bulbar muscles continue to weaker, it becomes more difficult to chew and swallow without choking. Choking almost always occurs when I am multi-tasking while eating.

I have also learned to live on the heels of my feet. The toes, for most people, provide balance when standing or walking. Since my toes can no longer hold my weight, I live a life trying to maintain my balance with most of my weight on my heels. Standing with my weight on my heels is often dangerous because it is easier to lose your balance. I have to focus on keeping the knees locked, weight on heels, weight on both legs, while being aware of my surroundings. When focused, I can feel almost every muscle in my legs and feet working (the motor neurons are firing). Another rule is that I cannot twist or turn while trying to walk. Today, one of the most frightening half-seconds in my life is when a knee buckles and I wonder if I am going straight down (the most dangerous fall), or fall forwards or backwards.

Perhaps you noticed that the word "focus' was used several time in this article. Focusing does not come naturally in a multi-tasking world. For someone with Kennedy's Disease, the adage about "not being able to walk and chew gum at the same time" takes on a completely new meaning. I would venture a guess that most falls occur when the mind is not focused on standing or walking.

You learn to live with these concerns and issues when you have Kennedy's Disease. You also find yourself constantly re-evaluating your capabilities as your strength wanes. While still being aware of these things, you try not to give them too much importance. You want life to be as normal as possible. I hope you understand that I am not complaining. I am just trying to remain focused.

Glimmers of Hope - Part III

Profiles of Kennedy's Disease Researchers

In this post, I wish to recognize another researcher who is carrying the baton:

Parsa Kazemi-Esfarjani, B.Sc., Ph.D., is a researcher for the Department of Pediatrics, Division of Genetics, Institute for Genomic Medicine at the School of Medicine, University of California, San Diego.

Author's Note: This post is a little longer than normal, but I did not want to edit it to a point that Parsa's enthusiasm on the topic was lost.

Bruce: Why did you decide to focus your research on Kennedy's Disease?

Parsa: My entry into the Kennedy's Disease community was a great coincidence. In 1990, as a master's degree candidate, I was looking for a lab and a research program where I could learn the cutting edge techniques in molecular biology and genetics, and a program with a direct relevance to human disease.  I found all of that in Leonard Pinsky's lab at Lady Davis Institute, McGill University, in Montreal.

In Kennedy's disease, the repeat stretch consists of the amino acid glutamine, also called a polyglutamine).  As I was planning and designing experiments such as deleting the various repeat tracts, including the polyglutamine tract, and studying how they affected the function of the androgen receptor in cell cultures, I came across the report in the journal 'Nature' by Al La Spada and Kurt Fischbeck and their colleagues. Al's publication was a great impetus for me to ramp up my work and focus it on the notorious polyglutamines. Len Pinsky did warn me that the new discovery would generate a great deal of interest among scientists and a high level of competition, but I was young and daring and plunged right into the fray.

Even though I am presently not as youthful as I was then, I believe I am still daring! That is why over the past three years, I have concluded that the next frontier for Kennedy's Disease and other neurodegenerative disorders is the exploration for a safe and effective gene therapy system. We have plenty of therapeutic candidate genes, genetic drug targets, and other nucleic acid and protein derivatives, such as RNAi systems and neuroprotective peptides. It is time to put all of them to good use by properly delivering them to their intended targets.

Bruce: Briefly summarize what you are currently working on and why you feel it is important in KD research.

Parsa: As I mentioned above, my ultimate, long-term goal for the foreseeable future is to develop an effective and safe gene therapy so we could take advantage of the hundreds of candidate therapeutic genes that we have discovered over the past decade. These genes have been discovered through a remarkable international effort and at a high cost: 1) employing genetic screens in cell and animal disease models, such as yeast, worms, fruit flies; 2) using the new bioinformatic tools to compare the expression of thousands of genes at once in the disease and healthy tissues; and 3) adopting the candidate gene approaches in cell culture and animal models, examining the genes with suspected disease application based on prior knowledge.  However, the research grant proposal that I submitted to Kennedy's Disease Association also addresses a crucial aspect of gene and cell therapy: which cell populations or tissues contribute to the toxicity by the expanded-polyglutamine androgen receptor, and ultimately to Kennedy's disease? And, to what extent they do it?

Once we know the answer to these questions, we can redeploy our resources to develop the therapeutic agents and vectors for the appropriate cell and tissue targets.  In that way, we shall increase the probability of a positive clinical outcome in patients and simultaneously reduce the odds of seeing negative side effects.

 Bruce: What are your aspirations (career goals)?

Parsa: Based on the guerrilla tactics that are required to make leaps, as oppose to small incremental advances, in a complex field such as gene therapy for neurodegenerative disorders, I could not have asked for a more nurturing and positive environment than Al La Spada's lab and UCSD. As a research faculty, I would be able to devote my full attention to validating genetic and cellular therapeutic targets and collaborate with our colleagues to develop the long-sought systemic gene delivery for neurodegenerative disorders such as Kennedy's Disease.  Establishing effective gene therapy tools and strategies would open the doors to future combinatorial gene therapy to improve efficacy and safety by delivering multiple therapeutic genes at once, with each gene expressed at a much lower, less toxic, level, hence less side effects in patients. To continue my career in this line of effort, in time, I shall seek a well-funded position in an institute with a superb research infrastructure and outstanding colleagues and trainees with whom I can intellectually engage and collaborate.

 Bruce: You are a strong advocate of Gene Therapy. Would you care to comment on where we are at with this opportunity?

Parsa: With respect to the current state of gene delivery to the central nervous system, we are still fighting The Great War, flying biplanes and dropping 20-pound bombs on the enemy (i.e., poylgutamines, Abetas, prions, etc.).

With Al La Spada's support, one of my missions in our new theatre of research at UCSD is to mobilize a collaborative research project among the topnotch faculty at UCSD and its affiliates to develop a more advanced gene therapy system. The new vectors, a combination of viral and non-viral vector technology, could be administered intravenously (by injecting into veins as opposed to intracranially (through the skull) or intrathecally (through the spinal canal)) and the vector carrying the therapeutic genetic cargo would be distributed through the CNS via its microcapillaries and across the blood-brain barrier.

A tremendous amount of groundwork has already been done by diverse groups of researchers with the same enthusiasm about the prospects of gene therapy: geneticists, biochemists, chemists, molecular biologists, virologists, engineers, pathologists, etc. It is only a matter time and our determination to put all the available technology together to create clinically applicable gene delivery systems. In fact, there are several publications in the recent years that show success in systemic gene delivery in preclinical research.  (If you care to learn more about this, comment below and I will post the publications referenced)

 Bruce: Is there anything else you would like to mention?

Parsa: For most scientists, the human face of the medical research is the ultimate motivating factor. When experiments fail, funding is not granted, a manuscript is not accepted, or one simply yearns to leave the office or lab in the evening and join the family; thoughts of other families who depend on this research and its outcome, provides the mental fuel for those tougher extra miles.

Education and Awareness

Many inquiries that I receive are from spouses or caregivers needing additional information to help their loved one that has Spinal Bulbar Muscular Atrophy (aka Kennedy's Disease). Occasionally, I receive an email from a facility that is caring for a person with Kennedy's Disease. I am most appreciative of these caregivers because they are taking the time to research and understand what a person is going through that has the defective gene.

This summer I received such an email. A caregiver in a nursing home asked a series of questions about how Kennedy's Disease affects a person. We exchanged several emails. Her final email was interesting because she commented that many of the staff felt the person with Kennedy's Disease was 'faking it' (my term) and they were frustrated with the patient. After reading my responses and looking through the Kennedy's Disease Association web site, she now better understood the physical and emotional issues a person with Kennedy's Disease goes through. Two specific areas that frustrated many of the caregivers were: (1) the almost daily comments from the patient concerning muscle pain (constant aching), and (2) the frustration the patient exhibited with not being able to perform simple tasks. The caregivers could not understand why the patient would continually try to do something that he just could not do. One example was walking … and as a result occasionally falling.

As I mentioned, fortunately she took the time to do some research including contacting the Kennedy's Disease Association to help her understand more about the disease. In her last email, she commented she now was taking on the task of educating the rest of the staff about Kennedy's Disease.

This incident makes me wonder about others with Kennedy's Disease that might be in a nursing home or facility where the staff is unaware of the effects of the disease on the patient. It amplified the need to constantly educate others concerning Kennedy's Disease ... especially those in charge of your care (in a hospital, nursing home, and even your doctor's staff).

From personal experience, I know that we have to be the caretakers of the disease. When I broke my tibia and fibula in a fall a few years ago, the doctors were ready to wheel me into the operating room to repair the leg. I told my doctor that the anesthesiologist needed to be aware of my condition and only use anesthesia that was known to be safe for someone with my condition. I also instructed the doctor about keeping me warm because hypothermia is another concern for those of us with the disease. I had my wife bring a file on the surgical concerns of operating on someone with the disease to inform the doctors of known issues. If I had not said, "Time Out," the surgery might have caused me more harm than good.

I now carry a medical card in my car and wallet. It explains that I have Kennedy's Disease as well as concerns that need to be addressed before administering anesthesia and operating on me. I highly recommend that anyone with this condition print the information found on the Kennedy's Disease Association website regarding anesthesia and give a copy to your doctor.

The Boy Scout's motto is "Be Prepared." Are you?

Trust

The dictionary defines 'trust':

• Noun – Certainty based on past experience, complete confidence in someone or something
  
• Verb – Having confidence or faith, being confident about something, to allow without fear
  
  

Once you have been betrayed trust is not so easily given again. If you have been burnt four, five, six times or more, it is almost impossible to ever trust again. Nevertheless, that is what I am trying to do. And, so far, everything is just fine. Will I be betrayed again? Probably. Yet, every day that goes by without an incident or betrayal sure feels good.

For a person that has fallen close to fifty times in ten years, it is not easy to trust that my legs will hold me up. The hardest part of trusting those muscles again was overcoming the fear that the next fall could mean another serious injury. That fear still lingers in the back of my mind, but every day I am on my feet provides a little more confidence.

The last time I fell, I broke my tibia and fibula. The fall occurred two weeks after I just had my last cast removed (for a broken fibula and anklebone). I had just begun walking again when the quads gave out and I went down. The recovery this time (90 days without being able to put any weight on the leg) was very difficult for me and even more difficult for my wife. Ever since that fall, I have been extremely cautious to the point of not taking more than a few steps without some mobility aid.

But, trust is what my physical therapist wanted me to do last November when he asked me to walk around the house again with a walker and then with a cane. I remember that first day very well because I was nervous. I just did not have any confidence in my leg strength and the fear of another long rehab lingered with every step I took.

Ten months later, I am more confident in my leg strength than I have been in years. The exercise program the physical therapist provided, and I practice daily, is a success. Remarkably, I feel stronger today than two years ago. Daily, however, I still need to remind myself to trust that my quads will not let me down.

Confidence is one thing. Over-confidence, however, is dangerous for those of us with Kennedy's Disease. Perhaps "cautiously optimistic" would be a better way to say how I feel today. And, every day that passes without an incident, "sure feels good."

The Future (Robotics) Is Nearer Than You Think

Two new devices that could eventually help those of us that are physically handicapped will soon be available. Two of the devices that are revolutionary in concept use robotics to assist a person in their normal daily functions. The prototypes were designed for other uses, but eventually both of the units discussed below could be used for rehabilitation, the elderly, or those of us with a neuromuscular disease.

Honda Robo-Leg - http://corporate.honda.com/press/article.aspx?id=4987. Honda just updated their videos to show both of their products in action. Check it out: http://corporate.honda.com/innovation/walk-assist/ Information from the web site follows:

• The robotic geeks at Honda have developed an exoskeleton that is worn like shoes to support the body and protect the joints; something the automaker says could reduce injuries on assembly lines but also might help the elderly get around more easily.  The device resembles a bicycle seat joined to a pair of shoes and fits suggestively between the legs to help the user walk, crouch and stand without excessive stress on the hips, knees and ankles. Honda is testing the "walking assist device" at a vehicle assembly line in Sayama, Japan, and says robo-legs could help anyone who spends a lot of time on their feet. More than that, it could help the elderly and infirm by making it easier to get around.
  
• "This should be as easy to use as a bicycle," engineer Jun Ashihara said during a demonstration at Honda's headquarters in Tokyo. "It reduces stress, and you should feel less tired." And, it might be the only mobile technology that is geekier looking than a Segway.
  
• Beyond serving as an ergonomic support for factory workers, Honda's third leg could have practical applications as potential replacement canes and walkers. Medical researchers have been working on walking-assistance technologies for decades.
  
  

HAL (Hybrid Assistance Limb) Exoskeleton -
http://www.cyberdyne.jp/englis...otsuithal/index.html This device can only be leased today, but there are rumors that it will be going on the market for $4,200 (US). Information from the web site follows:

• "Robot Suit HAL" is a cyborg-type robot that can expand and improve physical capability.
  
• When a person attempts to move, nerve signals are sent from the brain to the muscles via motor neurons, moving the musculoskeletal system. At this moment, very weak bio-signals can be detected on the surface of the skin. "HAL" catches these signals through a sensor attached on the skin of the wearer. Based on the signals obtained, the power unit is controlled to move the joint with the wearer's muscle movement, enabling to support the wearer's daily activities. This is what we call a 'voluntary control system' that provides movement interpreting the wearer's intention from the bio-signals in advance of the actual movement. Not only a 'voluntary control system', but also a 'robotic autonomous control system' that provides human-like movement based on a robotic system that integrally works together with the 'autonomous control system'. "HAL" is the world's first cyborg-type robot controlled by this unique Hybrid System.
  
• "HAL" is expected to be applied in various fields such as rehabilitation support and physical training support in medical field, ADL … support for disabled people.
  
  

Both units have a battery life of about two hours, but that should improve over time. Having to stop every couple of hours to replace your battery would not be very convenient. The other concern I have is balance. Since we have balance issues (toe and ankle strength), would devices like this help? Yet, these type devices are exciting because it opens the door to other potential innovations.

Can you imagine the look you would get walking into a Wal-Mart wearing either one of these gadgets?

Glimmers of Hope - Part II

Profiles of Young Researchers

In an earlier post called, "The Nine Stages," I mentioned "Hope" was the ninth stage. I ended the post by saying, "With acceptance, and armed with the additional knowledge that researchers were working diligently towards finding a treatment and potentially a cure, I discovered something that had been missing recently in my life – Hope." In another post, "Another Ray of Hope on the Research Front," I commented, "how fortunate we are that another generation has picked up the baton and continues to move towards the finish line (finding a treatment or cure). As long as someone is carrying the baton, we have hope."

In this post, I wish to recognize another researcher who is carrying the baton:

Isabella Palazzolo, Ph.D., is a researcher for the Massachusetts General Institute for Neurodegenerative Diseases (MIND), at the Massachusetts General Hospital, Harvard Medical School, in Charlestown, MA.

Bruce: Why did you decide to focus your research on Kennedy's Disease?

Isabella: My first interest, when I was still in undergraduate school, has always been the neurons. When I met my first mentor, Angelo Poletti, I discovered the motor neurons, and I found it extremely interesting how those tiny cells in our spinal cord can modulate the movements of all our body for our entire life. I think the equilibrium inside those cells is amazing and I am really curious to understand it better, to find what goes wrong in disease and how to fix it.

Bruce: Do you personally know anyone with Kennedy's Disease?

Isabella: I feel lucky, because three years ago I had the occasion to join the KDA meeting. That event gave me a bunch of new reasons to study and work on Kennedy's disease. Everyone that I met, patients and patients' families, was and is a real example of dedicated, lovely, brave people. I believe the meeting with you guys (the KDA Conference) in Atlanta 2006 was really the changing point for my scientific life.

Bruce: Briefly summarize what you are currently working on and why you feel it is important in KD research.

Isabella: I've been working for the past three years in Dr. Fischbeck's lab, under the supervision of Maria Pennuto. Both these people should be acknowledged for what I have done so far. As I said before, my starting point is the equilibrium in the motor neuron. I believe it is extremely important to imagine being in the motor neurons: there, the AR is in solution, and in contact with other proteins around it. It is charged, positively and negatively, and the charge on the surface regulates the way it communicates and interacts with other proteins. When polyQ is expanded, interactions between proteins change and the AR becomes toxic. So, I decided to study how I can change them again, in order to reverse/counteract the toxicity of the polyQ. I think that attaching a phosphate group [phosphorylation] or a molecule of ubiquitin [ubiquitination] is a good tool to change protein-protein interactions. Thus, I studied the consequences of AR phosphorylation by Akt, a kinase that was protective in Huntington's Disease also. We found that this phosphorylation is indeed protective, in cells, in flies and in a mouse model with SBMA (Kennedy's Disease). My interest now is to understand why, what happens to the phosphorylated-AR in the motor neurons. I think this study is important because it highlighted a potential therapy for SBMA (Kennedy's Disease). Akt activity can be stimulated by Insulin-like growth factor I (IGF-1), and we demonstrated that IGF-1 is protective in cells and mice. I also think it is important to identify what happen to the phosphorylated AR as this might identify new targets for therapies, and will hopefully help to understand the mechanisms of the disease.

Bruce: What are your aspirations (career goals)?

Isabella: I really like translational research. Now, I have just started my PhD and I did bring some SBMA in my new lab. I would love to keep working on neurodegenerative diseases and SBMA in particular. My long-term question is once again how can I use post-translational modifications [=phosphorylation/ ubiquitination/ ecc] to target mutant proteins and reduce their toxicity, and what is the mechanisms behind.

Bruce: Is there anything else interesting you would like to mention?

Isabella: I would like to thank once again all my previous and current mentors: Angelo Poletti, for teaching me all that I know about the AR, Maria Pennuto and Kurt Fischbeck, for being such great examples of successful and determined scientists, and Dimitri Krainc, for is open-minded approach to science and for giving me the possibility to keep working on SBMA in his lab. Last, but not least, thanks again to the KDA association meeting. It is really motivating.

Self Confidence

When I was in my early thirties, I did not lack in self-confidence. In fact, when it came to playing racquetball, tennis, and my work, I was at the top of my game. From being a pilot to climbing mountains, there were few limitations. I was in control of my life and life was pretty darn good.

Today, if I can open a jar of pickles without my wife's help, I am ready to do a victory dance around the kitchen (that is if I could still dance). A great accomplishment these days is to replace a handle on the lawnmower or perform a minor repair on my wheelchair.

I have said it before, but I believe the mental and emotional aspects of living with Kennedy's Disease are as difficult as the physical issues. As I lose confidence in my abilities to perform simple physical requirements (e.g., safely walk from the car to a building or even stand up from a chair), I begin to question everything about my life. For years, I tried to compensate for my weakening state, but after many falls and several serious injuries, I realized that some so-called 'normal' activities just could not be performed without some assistance.

For example, in my final few years of working, any stairs, whether three or thirty, were out of the question. Walking long distances wiped me out. Those short little 'wheeled' meeting room chairs would force me to stand through a meeting because I knew I could not get up afterwards without help. As I became a little smarter, I found myself scoping out all the walkways and looking for alternative entrances and elevators within a building. I found a chair with a pneumatic lift and wheeled it into all meetings. I paid a terrible price for not being willing to say, "I can't." My life was one little 'white lie' after another until I finally decided to express my limitations. And, after I finally did, the world did not end. Actually, I found everyone was very kind, understanding, and accommodating. If only I had been more open and honest about my situation earlier in life, it might have been a lot easier.

Living with Kennedy's Disease is a never-ending learning process. You learn not to take anything for granted. Losing one's confidence is not so bad either. By questioning your abilities to perform a specific task, it forces you to evaluate the safety of the attempt.

Glimmers of Hope - Part I

Profiles of Young Researchers

In an earlier post called, "The Nine Stages," I mentioned "Hope" was the ninth stage. I ended the post by saying, "With acceptance, and armed with the additional knowledge that researchers were working diligently towards finding a treatment and potentially a cure, I discovered something that had been missing recently in my life – Hope." In another post, "Another Ray of Hope on the Research Front," I commented, "… how fortunate we are that another generation has picked up the baton and continues to move towards the finish line (finding a treatment or cure). As long as someone is carrying the baton, we have hope."

Over the next month or so, I plan to post profiles of some of the younger researchers who are dedicated to finding a treatment for Kennedy's Disease. Most of these profiles are in the researcher's own words except for some editorial license that I take. I do not imply that I know all of the younger researchers and have not selected any specific researchers over others. I just contacted a few that I am aware of and asked if I could profile them in my blog.

I decided to profile these researchers for two reasons. The first is to recognize this next generation of researchers who continue to provide us with hope. And, second, to let others that live with Kennedy's Disease know that there are people out there that are being passed the baton and readily accept the responsibility.

In this post, I wish to recognize:

Udai Bhan Pandey, Ph.D., who is an Assistant Professor at the Department of Genetics at Louisiana State University Health Sciences Center, in New Orleans, LA. Udai has been awarded two research grants from the Kennedy's Disease Association (KDA). Udai trained under J. Paul Taylor, MD, Ph.D., at the University of Pennsylvania and then St. Jude Children's Research Hospital. Note: Dr. Taylor is a member of the KDA's Scientific Review Board.

Bruce: Why did you decide to focus your research on Kennedy's Disease?

Udai: As a graduate student, I worked on another triplet repeat expansion disease "Fragile X Mental Retardation" that led me to think how expansion of triplet repeats in different proteins causes so many different human diseases. Soon after my graduation, I came to Dr. J Paul Taylor's lab for postdoctoral training. Dr. Taylor was planning to make a drosophila model of Kennedy's Disease. I was excited with the idea of using fruit flies as a model for studying Kennedy's Disease and decided to focus my research on Kennedy's Disease. The drosophila model of SBMA was made with the generous support of the KDA. KDA fellowship allowed me to initiate a genetic screen that led to the discovery of a novel gene HDAC6.

Bruce: Briefly summarize what you are currently working on and why you feel it is important in Kennedy's Disease research.

Udai: My lab is studying pathways responsible for degradation of Kennedy's Disease causing protein. We recently identified a novel gene HDAC6 that links two important pathways (ubiquitin proteasome system and autophagy) responsible for degradation of toxic and misfolded proteins. We are trying to identify genes that are involved in mediating HDAC6 function. In addition to this, we are also going to perform a large drug screen using Kennedy's Disease flies to identify compounds (drugs) that can protect against Kennedy's Disease.

Bruce: What are your aspirations (career goals)?

Udai: My lab at LSU is dedicated to research on Kennedy's Disease. My long-term goal is to develop a therapeutic intervention for Kennedy's disease. I am also planning to involve new people who are interested in working on Kennedy's Disease. Recently, Nicholas Lanson, Jr., Ph.D. joined my lab. Nick is a highly experienced scientist and he is very interested in doing research on neurodegenerative diseases, particularly on Kennedy's disease.

The Social Security – Disability Application Process – Part II

In my last post, I discussed how to make the Social Security – Disability process work for you. In today's post, I want to provide a few more tips to help speed up the qualification process.

Preparation is the key - As mentioned yesterday, 'preparation' is half the battle. Below are several comments on how to help ease the reviewer (and others) through your disability application process. The easier it is for them, the easier it will be for you.

• Discuss your intentions with your manager or supervisor and the need for their support. You do not want anyone to be surprised.
  
• Advise your doctor(s) and his/her staff that you are applying for Social Security-Disability benefits. Ask the doctor(s) for his/her support. Review (preferably in written form) your current symptoms and any health-related issues that affect your ability to perform your current duties.
  
• In the initial submission, provide the reviewer with as much information as possible – the more the better in this case. The more information the reviewer has to work with initially, the less information he/she has to write off for – meaning a delay in the process. The more information requested by the reviewer, the greater the chance the doctor's office will not be able to find it and/or it will be delayed.
  
• If you control the information flow, you can make certain the most important information is in the front and that the important sections (information) are highlighted so the reviewer can easily find the critical information he/she needs to make a decision. Make certain the information submitted is readable and prioritized – in the order you want it presented. Be sure to sign and date all the forms.
  
• Use the 'Supplemental Section' to educate the reviewer on what Kennedy's Disease (SBMA) is, its symptoms, its treatment, etc.
  
• Provide the information in a 'report' format – tabbed, with page numbers and a table of contents, etc. - so the reviewer can easily locate the information he/she is looking for. Prepare a three-ring binder with the major sections tabbed. This will keep all of your information in one place and easy to find. The information should be in the same order and page numbers as submitted with the disability application. Keep a copy of everything submitted – just in case.
  
• If called, refer to the information by section and page number so the reviewer can easily find the information he/she is looking for.
  
• Take the binder with you to any reviews or hearings.
  
• Be patient and responsive to follow-up inquiries by the reviewer.
  
• If needed, follow-up with your doctor(s) and supervisor to insure they have provided the requested information.
  

How long does the process take? It generally takes longer to process claims for disability benefits than other types of Social Security claims - plan on 60 to 90 days. You can help shorten the process by bringing certain documents with you when you apply and helping the SSA to get any other medical evidence you need to show you are disabled. These include:

• Your Social Security number and proof of age
  
• Names, addresses and phone numbers of doctors, hospitals, clinics and institutions that treated you and dates of treatment
  
• Names of all medications you are taking
  
• Medical records from your doctors, therapists, hospitals, clinics and caseworkers
  
• Laboratory and test results
  
• A summary of where you worked and the kind of work you did
  
• A copy of your W-2 Form (Wage and Tax Statement), or, if you are self-employed, your federal tax return for the past year
  
• Dates of prior marriages and births of your children
  

Do not become frustrated. It is not uncommon to initially be denied. If that happens, schedule a meeting with your local Social Security Representative to review your application and ask for their opinion why the application was denied. Try to remove your emotions from this discussion. It is easy to become frustrated and start blaming the system or others, but try not to do it. Work with your representative to resolve any known issues with the application or concerns with your claim. The representative can be a great advocate. Then, file an appeal.

I hope this brief post helps to explain the process and some key 'learnings' based upon my experience. To learn more about the application process, contact your local Social Security Administration office, by going online to (http://www.ssa.gov/disability/) or, by calling 1-800-772-1213. The PDF guide I wrote can be found here: http://www.kennedysdisease.org/images/stories/PDFs/Social_Security-Disability.pdf.

The Social Security – Disability Application Process – Part I

Social Security – Disability (SS-D) is important to many of us who have to retire early because of health related issues (i.e., Kennedy's Disease). A few years ago, I wrote a 'guide' for applying for SS-D based upon my experience. Since the guide is twenty pages long, in this post I will try to focus on a few key 'learnings' that might make the process easier for you if you ever need to apply. At the end of Part II, I will provide a link to the actual PDF guide.


First, it is important that you understand how Social Security defines 'disability'. That is because other programs have different definitions for disability. Some programs pay for partial disability or for short-term disability. Social Security does not. Disability under Social Security is based on your inability to work. You will be considered disabled if you cannot do work you did before and they decide that you cannot adjust to other work because of your medical condition(s). Your disability also must last or be expected to last for at least a year or will result in death. [Note: Progressive disorders are different and this is why you need to work with your doctor and your Social Security representative in order to explain the gradual and continual loss of certain functions]


Here is how to make the process work for you:

A doctor who reviewed disability claims for a Fortune 100 company gave me the following advice on the disability application process.

• Apply immediately – do not wait until you are totally disabled before beginning the process.
  
• Be patient. The process takes time. It is not uncommon to wait 90-120 days before hearing the results of the application.
  
• Take the time to fill out the forms completely. The disability process is no different from any other application process (e.g., home loan, employment, etc.). Leave little to interpretation.
  
• Remove your emotions from the application process. Think of it as a business deal – your business. Learn the rules of the game and make the rules work for you. The 'red-tape' and follow-up letters asking for additional information are all part of the game.
  
• Understand how the forms are written. The disability process is written for people with a sudden illness or disability – not for people with progressive illnesses where there is no treatment or cure.
  
• Understand the process. Remember that the Social Security Administration is a government agency. Many applications are denied the first time.
  
  

I will add three more comments based upon my experiences with the Social Security Administration.

• Document everything. The more information you can provide up front, the smoother the process will go.
  
• Take the time to educate the reviewer. Do not expect the reviewer to understand Kennedy's Disease or your specific situation. The reviewer can be an excellent advocate if she understands Kennedy's Disease and your disability.
  
• Be prepared. The more prepared and organized you are, the better the chance for approval. (My award was approved in six weeks)
  
  

In my next post, I will discuss:

• How to be better prepared
  
• How long the process should take
  
• Other tips to help speed up the process