2010

New research uncovers what may be a primary neuron-damaging insult that occurs in an inherited form of the devastating neurodegenerative disorder, amyotrophic lateral sclerosis (ALS).  The mutant superoxide dismutase (SOD1) protein is one cause of familial ALS.  Although mechanisms underlying mutant SOD1 neurotoxicity remain uncertain, this mutant protein is associated with the cell’s mitochondria, tiny intracellular energy-producing structures.  Investigators, lead by Professor Don W. Cleveland at the University of California San Diego, report in the current issue of the scientific journal Neuron that abnormally folded mutant SOD1 interacts with voltage-dependent anion channel (VDAC1), which is located in the outer membrane of the mitochondria.

This finding sheds light into possible molecular links between mutant SOD1 mitochondrial dysfunction and spinal motor neuron degeneration of inherited ALS.  This channel controls important metabolic and energetic functions between the mitochondria and the rest of the cell.  Interestingly, this same channel has been implicated in Parkinson’s disease where studies have shown that a protein linked to the disease called Parkin interacts with this channel.

“Our evidence demonstrates that reduced VDAC1 function and correspondingly reduced mitochondrial function are direct components of intracellular damage from mutant SOD1,” says Professor Cleveland.  “The finding that VDAC1 is a target for mutant SOD1 within the nervous system provides important insight into the mechanism underlying premature degeneration and death of motor neurons.”

These studies were performed in the mutant SOD1 rats using antibodies that specifically recognize the abnormally folded mutant form of SOD1.  Investigators were able to demonstrate a reduction in conductance through this channel.  The channel conductance was not affected in liver mitochondria, and previous studies have shown that abnormally folded mutant protein does not accumulate in liver mitochondria.  This suggests that this interaction only occurs with the abnormally folded mutant protein in the affected tissues in ALS.  Chronic mitochondrial dysfunction can lead to oxidative damage and neuronal degeneration.

“This study builds on earlier findings that mitochondria are critical players in the disease mechanism; however, the new findings highlight a novel mechanism and a potential new target for the development of therapies” commented ALS Association Chief Scientist Lucie Bruijn, Ph.D.

Sandra Lesher Stuban is an RN who was a 38-year old Lieutenant Colonel in the Army when she was diagnosed with ALS. She's the author of The Butcher's Daughter: The Story of an Army Nurse with ALS, in which she describes her journey openly and honestly.  Although she is completely paralyzed and uses a ventilator, she lives an active life as a writer, nursing leader and mother of a teenage son.

Q: I am having more difficulty swallowing. I think I will soon need a feeding tube. But I am nervous and feel like I am losing my fight against ALS.  Do you have any advice?

A: Sandra Lesher Stuban: A feeding tube, also known as a PEG (percutaneous endoscopic gastrostomy) or g-tube (gastric tube), is actually your way to win this one battle against ALS. ALS isn't defeating you, rather you are defying its paralyzing effects by using a simple comeback: the feeding tube. You can also look at a feeding tube as a pair of glasses. You could do without it but why make yourself miserable. Here are some general tips for living well with a feeding tube.

I am an advocate of keeping things simple. I know some people insist on pureeing the same food the family eats. However the same family mealtime dynamics can occur whatever the food choice. Therefore I recommend a liquid total nutrition meal such as Isocal, Nutren, Osmolite, and others. Plus, it's much easier for your loved one.

Caring for a feeding tube is very easy. Simply mix a few drops of liquid antibacterial soap with warm water then use a Q-tip to
clean the skin immediately beside the tube. Using tap water and Q-tips, remove the soapy fluid. And finally, dry the area with
 dry Q-tips. Do this every day. You can use apply gauze around the tube, but I suggest not using tape. The gauze will stay in
place if the split is on the bottom side of the tube.

If you have a length of tube lying on your abdomen, I find it convenient to loop the tube in a loose knot when not being used.
This keeps it from inadvertently being pulled during transfers.
     
As a precaution, it's best to take an acid reducer.  It's very easy for stomach acid to enter the tube tract. A feeding tube should be completely comfortable. If you feel burning or pain, this may be the cause.

Ask the Doc: Q & A with Edward Kasarskis, MD, PhD 

Dr. Kasarskis

Edward Kasarskis, MD, PhD is Director of the University of Kentucky ALS Multidisciplinary Clinic at Cardinal Hill Rehabilitation Hospital in Lexington, Kentucky, professor in the Department of Neurology at the University of Kentucky, and Chief of Neurology at the VA Medical Center in Lexington KY. 

Q: How can I slow the progression of ALS? I hear there is one drug that can make some difference now and then others might be on the horizon?

Dr. Kasarskis:  

This is a question every person with ALS understandably asks. Today there is just one drug approved by the FDA to extend life for people with ALS, and that is riluzole (Rilutek®).  Here we are in the 21st century and it seems we have drugs for just about everything, so it is especially frustrating for patients and families to learn that we don’t have more pharmaceutical options when it comes to slowing the progression of ALS and extending survival.  There are many studies being conducted now and new drug approaches are being tested.

Riluzole was approved based on two survival studies from the 90’s which demonstrated that riluzole extended survival compared to placebo. Some people read or hear about the results described in riluzole’s package insert and get discouraged, asking "is that all there is?" After the initial results were submitted to the FDA for the approval of riluzole, further research showed a consistent survival benefit from taking riluzole.

In the future, we will probably be treating ALS with combination therapy in much the same way oncologists treat cancer, not relying on a single drug to cure the entire disease.  It is also important to realize that during the initial studies of riluzole, ALS physicians did not employ multi-disciplinary care as aggressively as we do now. Life can also be enhanced and even extended by getting multi-disciplinary care, which addresses the full range of issues facing a person with ALS. 

Many clinical drug trials are in the development phases or are underway.  For example, ceftriaxone, an antibiotic already approved by the FDA, is under study to determine if it (alone or in combination with riluzole) will slow the progression of the disease. (Ceftriaxone has other effects, in addition to being an antibiotic, but ALS is not infectious). This is a multicenter study at 60 sites in North America coordinated by Massachusetts General Hospital and supported by the National Institute of Neurological Disorders and Stroke (NINDS). For more information, visit http://clinicaltrials.gov/ct2/show/NCT00349622.

You should discuss participating in this or other clinical trials in your area.  As patients, we all stand on the shoulders of other patients before us who volunteered their time and their bodies to participate in a clinical drug study to prove that our blood pressure medication, or our antidepressant, or our drug for ALS is safe and effective. Clinical trials typically require regular testing and evaluation. They usually provide great psychological benefit, just from participating in something that can further our understanding of ALS and could directly help you and other ALS patients in the future.

Cortney Mansfield, Activities and Volunteer Director at Brighton Gardens Assisted Living (Raleigh, NC) organized an ALS  Fundraiser Talent Show for residents on May 20, 2010 in honor of Diane Hardison.  Cortney invited residents and members of Diane’s family to participate as talent. Diane was the red carpet guest of honor and looked beautiful with her escort, Frank Hielema, Brighton Gardens Physical Therapist. Brighton Gardens Director, Karen Sherman served as emcee. The audience included residents, employees, and visiting families.

The event started with Gretyl Kinsey’s video of Diane talking about living with ALS in her own words. Furniture was then moved aside and the floor opened up as a stage to accommodate 12 acts of live music, dance, and comedy routines. Diane’s mom , Hazel Sorrell ( age 94), did a comedy act; Diane’s  brother, Todd Sorrell joined Rocky Tutor as a vocal duo; her brother-in-law  and nephew , Tony McLamb and Zach McLamb played bluegrass music on bass and banjo;  her sister, Marilyn Kinsey  danced as Michael Jackson; and her niece, Gretyl Kinsey played the piano and sang. Other acts included residents and employees who line-danced, played the piano, and sang; a blind-folded chef act; and a resident’s granddaughter who played the piano. All performers received small trophies. Gretyl Kinsey won the grand prize for her very moving video. The talent show was enjoyed by all and raised over $500 for Diane’s Team in the 2010 Triangle Walk to Defeat ALS®.  
 

The ALS Association has led the fight to establish a National ALS Registry, partnering with Congress and the Centers for Disease Control and Prevention to secure funding and to build the registry.   We are excited to report that the National ALS Registry is operational and has begun to identify cases of ALS across the country, including those who have lost their lives to the disease.  In fact, thousands of cases already have been identified through existing national databases, such as those for Medicare, Medicaid and the Department of Veterans Affairs.  

However, this is just the initial phase of the Registry.  The Centers for Disease Control and Prevention/Agency for Toxic Substances and Disease Registry (ATSDR) is now preparing to launch the National ALS Registry’s on-line web portal, which will enable all people with ALS across the country to self-enroll in the Registry.  The web portal is expected to “go live” later this year and will be available on the CDC’s ALS Registry website.  

The launch of the portal is the next phase in implementing the Registry.  Once fully implemented, the Registry will identify cases of ALS from across the country and collect data that is urgently needed to advance research into the causes of the disease and how it can be effectively treated.   Ultimately, the ALS Registry may become the single largest ALS research program ever created.  And it will mark the first time that data about ALS cases will be collected in such a comprehensive manner and on a nationwide scale.  

PALS Test ALS Registry Web Portal
At The ALS Association’s National ALS Advocacy Day and Public Policy Conference held in May, the ATSDR provided an update on the latest progress in implementing the Registry (Click here for the latest Registry Update).   The Agency also enlisted the help of several PALS attending the conference who tested a draft version of the online web portal.  PALS from Alabama, Maine, Mississippi, Nevada, and New Jersey provided feedback to the Agency on the ease of use of the portal, readability, layout and a number of other factors that will help to ensure that PALS and families can easily enroll in the Registry and that the Registry collects the vital information that will make it such a powerful research engine.

How Can PALS Enroll in the Registry?
To find out the latest information about the ALS Registry, including when PALS can begin to self-enroll, please sign-up to be an ALS Advocate via The Association’s website, here.   As an ALS Advocate, you will receive the most recent news about the ALS Registry.  And as the launch of the web portal approaches, The ALS Association also will provide detailed information about the Registry on our website, including answers to frequently asked questions, instructions on how PALS can enroll in the registry, flyers that can be shared at support groups, and other helpful information.     

We Still Need Your Help!
Although the Registry is almost fully operational, we still need your help!   That’s because Congressional funding is needed to continue enrollment in the Registry and to ensure the Registry provides vital information to researchers.   Thanks to your efforts, Congress already has provided $16 million over the past five years to design and launch the Registry.  But additional funding is needed and you can help by signing up to become an ALS Advocate.  By doing so, you will learn when your outreach to Congress can make the most difference.  And with your continued efforts, we can ensure that the Registry will fulfill the promise of helping to find the cause, treatment and cure for ALS.

The ALS Association directs the most comprehensive, global ALS research program ever organized with 80 scientific studies being funded right now. Here are a few recent achievements that are only possible because of the generosity of friends like you:

·         Conducting the first FDA-approved U.S. trial to treat ALS with spinal cord stem cells. This is a significant step toward delivering regenerative medicine directly to damaged neural cells in humans, and offers great promise for treating ALS.

·         Scientists organized and funded by The Association discovered a new gene, ALS6 (Fused in Sarcoma), responsible for about 5 percent of the cases of inherited ALS. The discovery will provide important clues to the causes of ALS.

·         The first ALS patient received a new therapy, Isis-SOD1RX Antisense Treatment, in a clinical trial. This is the first therapy that is specifically aimed at the SOD1 gene, known to cause an  aggressive, inherited form of ALS.

To learn more about the latest research and findings, visit www.alsa.org/research.

Ask the Doc: Q & A with Edward Kasarskis, MD, PhD 

Dr. Kasarskis

Edward Kasarskis, MD, PhD is Director of the University of Kentucky ALS Multidisciplinary Clinic at Cardinal Hill Rehabilitation Hospital in Lexington, Kentucky, professor in the Department of Neurology at the University of Kentucky, and Chief of Neurology at the VA Medical Center in Lexington KY. 

Q: My husband has difficulty accepting the need to adapt to ALS as it progresses. When the doctor or team members suggest he consider getting some additional help like a cane, or a wheelchair he bristles, and puts off the decision. What can I do?

Dr. Kasarskis: This is a common frustration. And it’s actually tough, since we all want to respect the person’s autonomy and their desire to make their own decisions. Typically, the family tries to let the person with ALS call the shots, but then finds they are getting increasingly anxious as they worry their loved one will fall, or choke on food, or have some other kind of difficulty.

Some people with ALS view recommendations to get a new assistive device, a PEG tube for feeding, or BiPap for breathing as a sign that they’re losing the battle with ALS. So they fight on without these aids. Their approach to the disease may reflect their decision-making style before being diagnosed with ALS. Sometimes someone’s coping style was extremely effective when they didn’t have the disease, but it doesn’t work well now.

It’s important to make sure your husband isn’t depressed, and your physician may want to prescribe an anti-depressive medication. It may also be valuable to have a formal battery of neuro-psychological tests done which may help you (and him) better understand any issues your husband may be dealing with. It is also possible that he may have developed a cognitive inability to make these kinds of decisions or to deal with his emotions effectively, a situation that can occur in people with ALS.

Too, you may both benefit from meeting with a counselor who can help you discuss the challenges you face together and assist you in effectively expressing your concerns about your husband’s tendency to delay getting the assistance he needs to effectively cope with his diminishing neuromuscular strength.

We do know that people with ALS must be good at solving problems because they face a variety of significant serial challenges. As Gilda Radner was fond of saying, “It’s always something.” The trick is to deal with issues as they arise by actively making decisions. Ignoring problems will not make them go away.

Ask the Doc: Q & A with Edward Kasarskis, MD, PhD 

Dr. Kasarskis

Edward Kasarskis, MD, PhD is Director of the University of Kentucky ALS Multidisciplinary Clinic at Cardinal Hill Rehabilitation Hospital in Lexington, Kentucky, professor in the Department of Neurology at the University of Kentucky, and Chief of Neurology at the VA Medical Center in Lexington KY. 

Q: I hear about so many claims on the internet for megavitamins, herbal remedies and supplements to slow ALS. They all look so promising. Do they help?

Dr. Kasarskis:  It’s not ridiculous to think that plants and natural products might have benefit in ALS. After all, many drugs used in medicine were originally derived from plants; For example, colchicine for gout comes from the autumn crocus (Colchicum autumnale, growing in my back yard), and digoxin comes from the foxglove plant (Digitalis lanata). But when we’re talking about using herbal remedies and supplements to slow the progression of ALS, we have to be careful. Virtually none of these products has been tested in persons with ALS.

Here is what we do know:

• Creatine has been tested in North American and Europe and no benefit was found in slowing the progression of ALS, although one study suggested it might increase muscle strength temporarily.
   
• Vitamin E, in very high doses, was studied in Europe, and showed a modest, but insignificant, benefit in slowing the progression of ALS. There may be, however, negative effects from such doses. An analysis of a wide range of Vitamin E treatment trials for a variety of conditions showed an increase in the risk of bleeding and stroke, raising safety questions.
   
• Co-enzyme Q10, at 2700 mg a day, was studied to see if it would slow ALS by 20% (using the ALS Functioning Rating Scale, revised, or ALSFRSr). That high degree of impact was not found, but a smaller benefit may have gone undetected since the study was designed only to determine if there was a very large benefit. Importantly, no adverse consequences were discovered. Although there may be some value in taking Co-enzyme Q10, it is expensive.

I know all of this is frustrating for ALS patients, their families, and their well-intentioned friends who want to be pro-active in managing the disease. This is very understandable. I just did a Google search on “ALS” which returned 6.8 million hits! The only way we will make real progress in this disease is through well-designed, controlled clinical trials. I strongly encourage your participation at an ALS Center near you —for yourself and for the future.

One of the challenges of ensuring mobility and access to what you most need is that the modern American home is often a bit cluttered. Tables, lamps, piles of books and magazines, and even decorations can all make it more difficult for people with impaired movement and mobility to have what they need at hand.

Here are some tips from organizing and design experts to help you simplify your home environment:

Remember, simplification means saving time and energy for  everyone.

• Create a place you love to be. It might be a sunny room with your bird in a cage, or perhaps a spot with a lovely view of the yard, a restful, cozy corner, or the best seat in the house, right in front of the big screen TV. Make it convenient, have the things you like to use right there next to you, and enjoy it!

• Make an organized effort to declutter. Ensure there’s room to get around your furniture and try to convert your home’s obstacle course into more of an open road.

• Put the things you need for certain activities all together, in a plastic carryall or a basket. That will make it easier for you and will also assist those who are helping you to have what you want when you want it. For example, you could have a plastic carryall with everything you need for a shave, or all your post-shower accessories, or even the items you need to send a bill or a note (right down to the pen and stamps).
 

For more ideas, refer to the following resources.
• Simplify Your Space by Marchia Ramsland
• Organizing Your Home by Emily Wilska