Ask the Doc:
Q & A with Edward Kasarskis, MD, PhD
Each issue we will feature a leading neurologist specializing in ALS responding to a question.
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: What should people with ALS know about fatigue? I seem to get much more tired lately.
Dr. Kasarskis: The term “fatigue” is broadly used to cover a wide range of situations, but for many people it means you just don’t have the energy level you once had. For some, it’s very specific: they realize they get especially tired walking into the grocery store, taking a shower or getting dressed in the morning.
Fatigue is a common concern among people with ALS. When muscles are working less efficiently and effectively, it can take additional energy to accomplish physical tasks of all kinds. You may be sleeping less efficiently, especially if you have muscle spasms or other issues during the night. If your breathing is somewhat compromised at night, that, too, can leave you feeling tired. Sometimes people with ALS find they are stressed and depressed, and those issues can also contribute to a sense of fatigue.
There are some things you can do to minimize the fatigue. First, pace yourself. Give yourself the extra time you need to accomplish things than you did before you developed ALS. Try not to get frustrated by the extra time it takes; keep reminding yourself that it is natural and expected.
Schedule a nap or two during the day to allow yourself to catch up and relax. You’re not being lazy; you’re re-charging your batteries. The relaxation will also help relieve stress and tension.
Consider using assistive devices to make things easier and help you exert less effort to complete a task. You may benefit by using a walker, a wrist brace, or other tools designed to help you save energy for the activities you most want to do. Sometimes it’s hard to make the decision to use an assistive device. You may feel you’re “giving in” to the disease or taking a step in the wrong direction, as some people say. But saving more energy and reducing fatigue will ultimately make life a lot easier for you.
And be sure to talk with your physician, and physical therapist, respiratory therapist and occupational therapist, if possible. Try to put into your own words what you see as causing your fatigue and describe what tasks are most exhausting. Don’t minimize your smaller problems, the little things that frustrate you or make life more difficult. Tell your doctor; he or she can then help find practical ways to manage those issues.
Each issue we feature a leading neurologist specializing in ALS responding to a question. If you would like to submit questions for a future Q & A, please send your questions to Amber Walters at awalters@alsa-national.org. Please understand that we won’t be able to address all questions and we won’t be able to respond to individuals personally. TOP
Dealing with Depression
Depression is common among people with ALS and their families. Estimates vary, but most experts estimate that more than a third of people with serious chronic illness experience symptoms of depression. It’s easy to understand. There’s so much to process, great adjustments in the way life is lived, frustrations and questions, and the necessity to rely more and more on others. Sometimes all of this is complicated by financial challenges and all the other issues with which everyone must grapple in everyday life.
The feelings are a very normal reaction to the stress of having ALS. Any loss of ability or function is experienced as a loss, and it all tends to add up.
The symptoms of depression are also often commonly seen with ALS itself: fatigue, poor appetite and insomnia. So it’s easy to be confused about whether the problem is largely ALS or is something more. Typically, people who are depressed experience:
- Fatigue or a decrease in energy
- Apathy (caring less about things in general)
- Difficulty concentrating
- Loss of interest in daily activities
- Sleep problems: restlessness, wakefulness, or sleeping more than usual
What should people with ALS who feel depressed do? It’s important to talk with your physician about your feelings. Sometimes issues directly related to ALS may be the cause, and solving those problems may improve your emotional state. Your care provider may be able to suggest modifications in your treatment or may refer you to physical, occupational or respiratory therapists who can make tangible improvements in your daily life. Your physician will also be able to help explore with you whether your depression should be treated more directly.
Antidepressants are frequently effective, especially when combined with “talk therapy” or counseling. Often the process of working through your thoughts and feelings with someone outside your network of family and friends can be helpful.
There are also some strategies that may be also help:
- Express your feelings, talk about your sense of frustration, grief, and loss.
- Set new, achievable goals. Plan for activities you can and will enjoy.
- Focus on your abilities, and use assistive devices to improve your quality of life and ability to do things by yourself.
- Don’t be a loner. See friends and family.
- Maintain your decision-making role. That alone reduces frustration and the sense of helplessness.
- Take care of yourself. It may take a lot of time and effort, but look your best. You’re likely to feel more social and more self-confident and upbeat if you do.
- Seek spiritual support. Prayer and meditation can be extremely helpful.
- Try not to isolate yourself. Involve your caregiver and family members in the effort to deal with depression together.
Remember that depression can be contagious. If family members are also depressed, they, too, should talk with their physicians and get help finding appropriate and necessary ways to deal with it.
People with ALS who have overcome depression say that the trick is to find a way to avoid focusing on the loss and to concentrate on the present, and the things you can and do enjoy. That may take time. But by talking with your physician and getting the help you may need, you may find yourself in the sunshine sooner.
Resources
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TREAT ALS® Program Supports New Clinical Trial
for ALS Patients Open for Enrollment
A clinical trial for patients with rapidly progressive forms of familial ALS has begun enrollment at Emory University. The study, using the drug arimoclomol, will specifically target ALS caused by mutations in the superoxide dismutase (SOD1) gene.
 This trial is being supported by The ALS Association as part of the Translational Research Advancing Therapies for ALS (TREAT ALS®) program.
Previous research has shown arimoclomol is effective in the SOD1 mouse model of ALS even when initiated after the onset of symptoms, and was found to be safe and well tolerated in a previous phase II clinical trial that included patients with sporadic ALS.
“We are very pleased to be able to test arimoclomol in patients with mutations in the SOD1 gene,” said Michael Benatar M.B.Ch.B., M.S., D.Phil., associate professor of neurology and epidemiology, Emory University School of Medicine.
“With this mutation, the diagnosis of ALS can be made with confidence based on less prominent clinical features, allowing initiation of treatment at an earlier stage in the disease process,” added Benatar, principal investigator for the study.
Lucie Bruijn, Ph.D., senior vice president of research and development for The Association, said the TREAT ALS initiative is designed to accelerate the clinical trial process with the objective of rapidly bringing new therapies to people with the disease.
“This is an exciting opportunity to learn more about the potential benefits that arimoclomol may have for treating people who have the familial form of this disease,” Bruijn said.
Previously, medications that have been found to be effective in the mouse model of ALS have not shown benefit when brought to human clinical trials. Benatar and dual-principal investigator, Merit Cudkowicz, M.D., Harvard Medical School, believe that the SOD1 mouse model of ALS most closely resembles SOD1-positive familial ALS in humans and hence this is the population most likely to benefit from arimoclomol.
According to Benatar, more than 90 percent of ALS cases are considered sporadic with a minority having a clear genetic cause. SOD1 mutations represent roughly 20 percent of familial forms of ALS.
The target population for this double-blind, placebo-controlled, phase II/III clinical trial is patients with rapidly progressive ALS due to select mutations in the SOD1 gene. The trial aims initially to recruit 30 ALS patients in order to evaluate drug safety and tolerability. Thereafter, approximately 50 more patients will be recruited. All study participants will be treated for a total of 12 months.
The ALS Association’s TREAT ALS initiative is a multi-faceted program that supports the development of compounds for FDA-approved clinical trial. It was the first program of its kind in ALS to help bridge the gap between laboratory research discoveries and treatment for ALS.
For more information about the ALS clinical trial at Emory, please send an email to fals@emory.edu. Additional information is also available at the clinicaltrials.gov website. http://clinicaltrials.gov/ct2/show/NCT00706147?term=Benatar&rank=1.
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New Gene Mutation Discovery by ALS Association
Consortium is Major Research Breakthrough
In one of the most significant breakthroughs in the recent history of ALS research, a consortium of scientists organized and funded by The ALS Association has 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 inherited ALS, which accounts for 10 percent of all cases, and sporadic ALS, which occurs in individuals with no family history of the disease and accounts for the other 90 percent of cases diagnosed.
"This is a momentous discovery in furthering our understanding of ALS,” said Lucie Bruijn, Ph.D., senior vice president of research and development for The ALS Association. “A new gene provides a new piece of the puzzle we can use to shed light on why ALS develops, and where to focus our efforts on creating new treatments and finding a cure.”
The results of this groundbreaking research were published in the Friday, February 27 issue of the prestigious journal Science. The project was led by Tom Kwiatkowski M.D., Ph.D., at Massachusetts General Hospital, and Robert Brown, M.D., of the University of Massachusetts School of Medicine, and ALS Association-funded researchers Caroline Vance, Ph.D., and Christopher Shaw, M.D., of Kings College in London. The project was supported by a consortium of leading ALS researchers from around the world, formed as part of The Association’s Gene Identification Project. Their success reflects an unprecedented effort to accelerate the search for genetic mutations linked to all forms of ALS.
Dr. Brown noted, “We are particularly delighted because our trans-Atlantic consortium has pursued the chromosome 16 gene for more than six years. The ALS Association has been an all-important partner in this search. This discovery should lead to new cell and animal models of ALS, which will accelerate drug development.”
“Global partnerships between investigators and funding agencies, such as the Motor Neuron Disease Association in the United Kingdom, are crucial to making these kinds of breakthroughs,” Dr. Bruijn commented. “This finding has opened up a whole new avenue of research and has the potential to uncover a common mechanism for most forms of ALS.”
The gene mutations were first identified by Dr. Kwiatkowski and were immediately confirmed by Dr. Vance, who also demonstrated abnormal accumulations of the mutant protein in cells cultured in the laboratory and the motor neurons of people carrying FUS mutations.
The gene, called FUS (“fused in sarcoma”), normally carries out multiple functions within motor neurons. These include regulating how gene messages (called messenger RNAs) are created, modified, and transported in order to build proteins. Some of these same functions also are performed by another gene called TARDPB encoding the protein TDP43, and mutations in the TDP-43 gene were recently linked to ALS as well.
“The fact that these two genes help perform the same function suggests that problems in this function may be critical in the development of ALS,” Dr. Bruijn said. “More research into exactly how these two genes work could ultimately lead to new treatments that are effective in slowing or stopping the progression of ALS and extending the lives of people with the disease.”
The mutations in the ALS6 gene were identified by detailed genetic sequencing in several families with an inherited form of ALS (familial ALS). Normally, the ALS6 protein works in the cell’s nucleus, but the mutations caused it to instead cluster outside the nucleus. Further work will be needed to determine precisely how this leads to ALS. With the gene in hand, scientists will be able to create cell and animal models containing the mutated gene, to examine in detail how the mutation operates and how it causes ALS.
“This suggests there may be a common mechanism underlying motor neuron degeneration,” according to Dr. Shaw. Motor neurons are nerve cells in the brain and spinal cord that control muscles. Motor neurons degenerate in ALS.
This is the second ALS-causing gene to be discovered in the past 12 months. SOD1, discovered in 1993, accounts for 20 percent of inherited cases of the disease. Mutations in the TARDP gene account for another four to five percent. The only well-defined causes of ALS are genetic. In both inherited and sporadic ALS, the disease symptoms and pathology are the same.
The possibility that ALS may be caused by several factors is the rationale for The Association’s policy of funding multiple genetic projects around the world and encouraging these leading geneticists to work together and share information to help locate disease-linked genes for faster, more accurate scientific results. By funding research on a global level, The Association helps put together “genetic pieces” of the ALS puzzle.
“Through our support of research such as this study, The ALS Association is committed to finding the causes of ALS, and using that knowledge to develop a cure as rapidly as possible,” Dr. Bruijn said. “We will build on the discovery of this new gene to carry that effort forward.”
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The ALS Association's mission is to lead the fight to cure and treat ALS through global, cutting-edge research, and to empower people with Lou Gehrig’s Disease and their families to live fuller lives by providing them with compassionate care and support. Click here to contact your local chapter, certified center or clinic.
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