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Living With ALS
Hello, my name is Buddy Sowell and I have ALS (Lou Gehrig’s Disease). In September 2007 I visited a Neurologist to get some answers as to why my muscles were persistently twitching. I had some muscle cramping & slight fatigue, but thought nothing of it. After some seemingly useless muscle strength testing, Dr Dooley looked at me with obvious concern on his face. I thought it was maybe the fact that he was in his upper 80s and he always looked that way…anyway, he suggested that I see a Neurology specialist named Dr. Robert Baloh at Washington University Medical Center. After some intense and painful testing and months of excruciating waiting… I was surprisingly diagnosed with ALS. “You’ve got to be kidding” I remember saying…
Never in a million years would I have guessed that something like this would have happened to me and to my family. My wife Lori and my daughters Carly and Casey are my entire world. I love them more than words can describe. They have all made me a better person. My prognosis is uncertain, but I will fight. My loving family doesn’t deserve this…so I fight for them.
Lori and I talked canididly about what we should do next. We decided to take advantage of what time we still have together and focus on having fun as a family. No more putting off travel plans. Let’s try to do as much as we can right now. I know people who have a “live for today” mentality, and I truly believe that we should all follow that philosophy. NEVER turn down a chance to have fun.
My dilemma: How do I tell my friends and family? Do I wait for the condition to worsen, or get the word out now and get the initial shock over with? I look normal, so maybe now would be a better choice before I’m in a wheel chair or look sickly. I don’t want anyone to look at me differently. I don’t want any special attention and I certainly don’t want anyone to feel sorry for me. (Thanks for those few who knew about me earlier and didn’t mention it.)
One of my fears is that someone will get the idea to offer up a special intention for me at church…and I’ll slowly sink into the pew. I appreciate the thoughts and prayers, but please don’t do that. I’ll find a way to get you back…
Seriously, my choice is to tell people as I see them or make contact by email. Since I don’t get out much, email seems the easiest way.
Now, on a more positive note, Dr. Baloh’s Lab has made progress in converting skin stem cells into nerve cells in mice. I know I’m not a mouse, but it’s a huge step. Once this science is further along, nerve cells (from stem cells) can be utilized to replace damaged nerve cells and hopefully find a cure for ALS and many other neurological diseases.
Just what is ALS? (Amyotrophic Lateral Sclerosis) is a motor neuron disease, first described in 1869 by the noted French neurologist Jean-Martin Charcot. Although the cause is not completely understood, the last decade has brought a wealth of new scientific understanding about the disease that provides hope for the future.
Lou Gehrig first brought national and international attention to the disease in 1939 when he abruptly retired from baseball after being diagnosed with ALS. Most commonly, the disease strikes people between the ages of 40 and 70, and as many as 30,000 Americans have the disease at any given time. This disease has cut short the lives of other such notable and courageous individuals as Hall of Fame pitcher Jim “Catfish” Hunter, Senator Jacob Javits, actors Michael Zaslow and David Niven, creator of Sesame Street Jon Stone, television producer Scott Brazil, boxing champion Ezzard Charles, NBA Hall of Fame basketball player George Yardley, pro football player Glenn Montgomery, golfer Jeff Julian, golf caddie Bruce Edwards, British soccer player Jimmy Johnstone, musician Lead Belly (Huddie Ledbetter), photographer Eddie Adams, entertainer Dennis Day, jazz musician Charles Mingus, composer Dimitri Shostakovich, former vice president of the United States Henry A. Wallace and U.S. Army General Maxwell Taylor.
ALS is a neurodegenerative disease that usually attacks both upper and lower motor neurons and causes degeneration throughout the brain and spinal cord. A common first symptom is a painless weakness in a hand, foot, arm or leg, which occurs in more than half of all cases. Other early symptoms include speech swallowing or walking difficulty. The biological mechanisms that cause ALS are only partially understood. The only known cause of ALS is a mutation of a specific gene: the SOD1 gene. This mutation is believed to make a defective protein that is toxic to motor nerve cells. The SOD1 mutation, however, accounts for only 1 or 2 percent of ALS cases, or 20 percent of the familial (inherited) cases. Familial ALS represents between five to 10 percent of all cases. The rest arise spontaneously and mysteriously, making seemingly random attacks on previously healthy adults. ALS can strike anyone, anytime.
Physicians have limited choices for treating ALS, and the options that do exist have come into use within the last 10 years. Studies suggest that patients’ length of survival and quality of life are enhanced by night-time breathing assistance early in the course of the disease and by aggressive application of alternate feeding options to assure good nutrition once swallowing becomes difficult. At this time, riluzole is the only drug that has been approved by the FDA for treatment of ALS. In clinical trials, riluzole has shown a slight benefit in modestly increasing survival time.
Stem cell and gene therapy are promising areas of research. In a variety of studies, ALS mouse models are being used to develop treatments that may someday lead to similar human clinical trials. Gene therapy is one field of research where The ALS Association is concentrating support for more study. If you would like to send a donation click here.
More significant advances of research into ALS has occurred in the last decade than all of the time since Charcot identified the disease. Advances in technology and the genetic revolution are aiding researchers in unlocking the ALS mystery. As more scientists focus on this perplexing disease, the outlook for new understanding brightens each day.
What Are Stem Cells?
Stem cells, also known as progenitor cells, are cells that have not undergone differentiation to acquire a specific structure or role; they have the potential to self-renew, divide, and differentiate into specialized cell types. They are also sometimes termed “pluripotential” or “undifferentiated” cells because they can differentiate and develop into various cell lines. The differentiation of stem cells into mature cells is tightly regulated; otherwise, intricate plants and animals, with their many interrelated tissues, organs, and systems, could not exist.
By contrast, mature or differentiated cells have acquired specific structures and roles, and in many cases have lost the ability to divide and replicate. Also in contrast to stem cells, malignant cells or “dedifferentiated” cells divide in an uncontrolled fashion, and rather than resulting in useful, differentiated, or specialized cells, these types of cells threaten to kill the organism.
Stem cell differentiation must be turned on, given direction, and turned off as needed in order to properly supply the basic building blocks of tissues in different organ systems. This requirement for precise regulation applies to an even greater degree to the differentiation of neuronal progenitor cells, because effective neural function depends on establishing precise linkages and interactions between different individual neurons and classes of neurons.
By definition, stem cells, including neuronal progenitor cells, are present in embryos. Stem cells may be found in umbilical cord blood. In adults, these cells are present in bone marrow and in other organs in which controlled self-renewal is needed. Neuronal progenitor cells have also been shown to persist into adulthood in specific brain locations near the ventricles where they support ongoing learning and the establishment of new memories through their division, differentiation, migration, and insertion into new circuitry.
Is There a Role for Stem Cell Therapy? Stem cells could help patients with ALS in several ways. Ideally, they could be induced to differentiate into lower motor neurons in order to replace those neurons that die because of ALS. Perhaps stem cells could rescue dying motor neurons by reconnecting these neurons to partly denervated muscle before it has died completely. Better yet, they could be induced to differentiate into upper motor neurons in the cortex and connect to the lower motor neurons.
Unfortunately, the expectation that stem cells will play such a regenerative role in patients with Lou Gehrig’s disease is unrealistic because of the complexity of the task, which presents obstacles that currently are insurmountable. A more realistic expectation for stem cells is that they play a supportive role in maintaining the viability of or extending the function of surviving motor neurons. The stem cells could be induced to differentiate into supporting cells, glia, or interneurons that might produce factors that would support motor neurons, or perhaps the stem cells themselves might produce such factors.
What Do Existing Data Suggest?
Recent data from Clement and colleagues show that in chimeric, genetically engineered mouse models, motor neurons carry mutated SOD1 genes and glial cells carry healthy genes. Survival is extended in these chimeric mice, as compared with nonchimeric mice in which all motor neurons and all glial cells carry mutated SOD1 genes. This finding suggests that if healthy stem cells could get to the spinal cords of patients with ALS, their survival might also be extended. It remains to be determined whether a mechanism that compensates for a particular genetic error would apply to sporadic patients without that error. Nevertheless, even if this form of therapy were effective only for patients with familial disease, it would be a great leap forward.
In previous experiments, intraspinal transplantation of neurons derived from a human teratoma cell line was shown to ameliorate dysfunction and extend survival in G93A SOD1 transgenic mice. Furthermore, the life span of G93A SOD1 mice was extended by intravenous administration of human umbilical cord blood. The cells were shown to have migrated into the spinal cord and brain parenchyma and survived 10-12 weeks after infusion. They exerted their beneficial effect even though only a low number of transplanted cells expressed neural antigens. In another study, Sertoli cells, which are not neuronal stem cells, were implanted in the spinal cords of SOD1 transgenic mice and were shown to provide temporary protection to motor neurons in their proximity. However, viable Sertoli cells were not present at the time when the animals died.
Preliminary trials with autologous hematopoietic stem cells have been reported in humans. In one, peripheral blood-purified CD34+ cells were injected intrathecally into 3 patients with ALS. None reported side effects after 6-12 months, but no clinical efficacy was reported. In another, 7 patients received intraspinal transplantation of autologous bone marrow-derived stem cells. Minor postoperative adverse events were transient, but muscle strength continued to decline. After 3 months, however, the investigators reported a trend toward slowing of the decline in the proximal muscle groups of the lower limb in 4 patients and a mild increase in strength in 2 patients. Lack of placebo controls and longer follow-up preclude any inferences of efficacy from this study and none were made by the investigators.
Stem Cell Research: Ethics, Economics, Policy, and Public Health
The ethics of performing human studies at this early stage of stem cell research have been questioned, emphasizing the risks of premature human trials. Reports of stem cell transplantation performed in China without peer review of objective data on each patient before, immediately after, and at specific long-term points following the transplantation do not provide sufficient scientific evidence to demonstrate that the treatment is safe and effective.
“It is critical that scientists and clinicians are cautious, plan rigorous studies, and most importantly focus on key laboratory experiments that will provide answers to the many challenges that still face this therapeutic approach,” wrote Lucie Bruijn, PhD, the Science Director and Vice President of the ALS Association. “For this therapy to be safe and have potential in the clinic, it is critical that the appropriate studies are conducted to learn more about the properties and complexities of the various stem cells.”
In response to limitations on the type of stem cell research that may be performed with federal funds, the American Academy of Neurology and the American Neurological Association — the 2 leading professional neurology organizations in the United States — have both gone on record expressing the belief that both embryonic and adult stem cell research should be pursued rigorously and under close scrutiny, while respecting the concerns of their members and the public, regarding important ethical principles and values pertaining to research with human embryonic stem cells.
The scientific concerns are 2-fold. First, because the realistic likelihood for success of any individual research effort is low, parallel research in multiple directions is imperative for the field to advance rapidly. The essence of research is trial and error, which operates by identifying ineffective directions and thereby focusing on those that hold promise. It is usually a long time between initiating research and realizing a successful treatment with clinical applications. Therefore, any delay in identification of a potentially effective therapeutic intervention translates into delaying treatments for patients with the diseases in question. Second, excluding particular types of research from federal funding may translate into an exclusion of this research from federal oversight and protections, which might lead to its migration overseas. This may be detrimental to individual patients and to the broader community of patients, clinicians, and scientists.
In November 2004, California citizens approved a referendum measure to issue bonds to fund stem cell research, including embryonic stem cell research at $300 million a year for 10 years. Since then, several other states (Illinois, New Jersey, Maryland, New York, Delaware, and Wisconsin) are considering, or being asked to consider, initiatives for state-funded stem cell research to fill the federal funding gap. This is motivated, in part, by the desire to remain on the forefront of medical research and avert a brain drain toward states that provide an economic environment more conducive to cutting-edge research. The ripple effect of the California initiative is expected to result in acceleration of stem cell research nationwide.
Stem cell research carries promise for patients with ALS and may result in the development of new treatments to slow the progression of the disease. This hope needs to be tempered with caution because of the early stages of stem cell research in general, and in ALS in particular, and because of the track record of the limited efficacy of all pharmacologic interventions in transgenic murine and sporadic human ALS. Meticulous attention to the ethics and scientific rigor of future stem cell research should be supported by clinicians, scientists, and participating patients alike.
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