Hi, my name is Buddy Sowell, and I have ALS (Lou Gehrig's disease). In September 2007, I visited a neurologist to get answers to the question of why my muscles are pushing hard. I had some muscle cramps and slight fatigue, but we didn't think about that. After some seemingly useless testing of muscle strength, Dr. Dooley looked at me with obvious concern on his face. I thought that perhaps it was a fact that he was in the older 80s, and he always looked that way ... anyway, he invited me to see a neurology specialist named Dr. Robert Baloh at the University of Washington Medical Center. After some intense and painful trials and months of agonizing expectations ... I was surprised by the diagnosis of ALS. "You must be joking," I remember saying ...
Never in a million years I would have guessed that something like that would happen to me and my family. My wife Laurie and my daughters Carly and Casey are my whole world. I love them more than words can describe. They all made me better. My prediction is unclear, but I will fight. My loving family does not deserve this ... so I fight for them.
Laurie and I talked about what we should do next. We decided to take advantage of the fact that we still have time, and focus on having fun in the family. No need to postpone travel plans. May we try to do as much as we can right now. I know people who have a mentality “alive for today”, and I sincerely believe that we all should follow this philosophy. NEVER refuse to have fun.
My dilemma: How do I tell friends and family? Am I waiting for my condition to worsen, or learn the word now and get an initial shock? I look okay, so maybe now it will be the best choice before I sit in a wheelchair or look painful. I do not want anyone to look at me differently. I do not want much attention, and I certainly do not want someone to feel sorry for me. (Thanks to those who knew about me before and did not mention it.)
One of my fears is that someone will get the idea to offer me a special intention in the church ... and I will slowly sink into the dock. I appreciate thoughts and prayers, but please do not do this. I will find a way to get you back ...
Seriously, my choice is to tell people how I see them, or contact them by email. Since I don't get much, email seems to be the easiest way.
Now, more positively, Dr. Baloh’s laboratory has made progress in transforming skin stem cells into nerve cells in mice. I know that I am not a mouse, but it is a huge step. As soon as this science is continued, nerve cells (from stem cells) can be used to replace damaged nerve cells and, hopefully, find a cure for ALS and many other neurological diseases.
What is ALS? (Amyotrophic lateral sclerosis) is a motor neuron disease, first described in 1869 by the famous French neurologist Jean-Martin Charcot. Although the reason is not yet fully understood, the last decade has brought a lot of new scientific knowledge about the disease, which gives hope for the future.
Lou Gehrig first brought national and international attention to the disease in 1939, when he suddenly emerged from baseball after being diagnosed with ALS. Most often, the disease affects people between the ages of 40 and 70, and up to 30,000 Americans fall ill at any point in time. This disease has reduced the lives of other capable and courageous people such as Hall of Fame pitcher Jim "Som" Hunter, Senator Jacob Javits, actors Michael Zaslow and David Niven, creator of Sesame Street John Stone, television producer Scott Brazil, boxing champion Ezzard Charles, basketball player NBA Hall of Fame basketball player George Yardley, professional footballer Glen Montgomery, golfer Jeff Julian, golfer Bruce Edwards, British footballer Jimmy Johnstone, musician Lead Belly (Huddie Ledbetter), photographer Eddie Adams, Dennis Day actor, jazz musician Charles Mingus, composer Dmitry Shostakovich, former US Vice President Henry A. Wallace, and US Army General Maxwell Taylor.
ALS is a neurodegenerative disease that usually attacks the upper and lower motor neurons and causes degeneration throughout the brain and spinal cord. A common first symptom is a painless weakness in an arm, leg, arm, or leg, which occurs in more than half of the cases. Other early symptoms include speech swallowing or difficulty walking. The biological mechanisms that cause UAS are only partially understood. The only known cause of ALS is the mutation of a specific gene: the SOD1 gene. It is believed that this mutation transforms a defective protein that is toxic to motor nerve cells. However, SOD1 mutation accounts for only 1 or 2 percent of ALS cases, or 20 percent of familial (inherited) cases. Family ALS accounts for between 5 and 10 percent of all cases. The rest arise spontaneously and mysteriously, making seemingly random attacks on previously healthy adults. ALS can hit anyone, anytime.
Doctors have a limited choice for the treatment of ALS, and the options that exist have taken effect in the last 10 years. Studies show that patients have increased survival time and quality of life by breathing at night at an early stage of the disease and aggressively using alternative nutritional options to ensure good nutrition when swallowing becomes difficult. At this time, riluzole is the only drug that has been approved by the FDA for treating ALS. In clinical trials, Riluzole showed little benefit in a moderate increase in survival time.
Stem cells and gene therapy are promising areas of research. In various studies, mouse ALS models are used to develop treatments that may someday lead to similar human clinical trials. Gene therapy is one of the areas of research in which the ALS Association concentrates support for more study. If you want to send a donation, click here.
More significant advances in the UAS study have occurred in the last decade than the entire time that has passed since the discovery of Charcot. Advances in technology and the genetic revolution help researchers unlock the secret of the ALS. As more and more scientists are focusing on this confusing disease, the perspectives of a new understanding are highlighted every day.
What are stem cells?
Stem cells, also known as progenitor cells, are cells that do not have intravenous differentiation to obtain a specific structure or role; they have the potential for self-renewal, division and differentiation into specialized cell types. They are also sometimes called “pluripotential” or “undifferentiated” cells, because they can differentiate and develop into different cell lines. Differentiation of stem cells into mature cells is tightly regulated; otherwise complex plants and animals with their numerous interconnected tissues, organs and systems could not exist.
In contrast, mature or differentiated cells have acquired certain structures and roles and in many cases have lost the ability to divide and replicate. In addition, unlike stem cells, malignant cells, or “dedifferentiated” cells that divide in an uncontrolled manner, and instead of resulting in useful, differentiated or specialized cells, these cell types threaten to kill the body.
Differentiation of stem cells must be turned on, set in the direction of and turned off as needed in order to properly supply the basic building blocks of tissues with various organ systems. This requirement for precise regulation applies even more to the differentiation of neural progenitor cells, since the effective neural function depends on the establishment of precise connections and interactions between individual neurons and classes of neurons.
By definition, stem cells, including progenitor neuron cells, are present in embryos. Stem cells can be found in cord blood. In adults, these cells are present in the bone marrow and other organs that require controlled self-renewal. It has been shown that neural progenitor cells are preserved in adulthood in certain parts of the brain near the ventricles, where they support continuous learning and create new memories through their separation, differentiation, migration, and introduction to new patterns.
Is there a role in stem cell therapy? Stem cells can help patients with ALS in several ways. Ideally, they could be differentiated into lower motor neurons to replace those neurons that die because of ALS. Perhaps stem cells can save dying motor neurons by reconnecting these neurons to a partially denervated muscle before it is completely dead. However, they can be made to differentiate into the 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 is an obstacle that is currently insurmountable. A more realistic expectation of stem cells is that they play a supporting role in maintaining responsibility or expanding the function of surviving motor neurons. Stem cells can be induced to differentiate into supporting cells, glia or interneurons, which can lead to factors that will support motor neurons, or perhaps the stem cells themselves can lead to such factors.
What do existing data offer?
Recent data from Clement and collections show that in chimeric, genetically modified mouse models, motor neurons transfer mutated SOD1 genes, and glial cells transfer healthy genes. Survival survived in these chimeric mice compared to nonchimeric mice, in which all motor neurons and all glial cells carry mutated SOD1 genes. This conclusion shows that if healthy stem cells can enter the spinal cells of patients with ALS, their survival can also be extended. It remains to be determined whether the mechanism that compensates for a specific genetic error will be applied to sporadic patients without this error. However, even if this form of therapy was effective only for patients with family diseases, this would be a big leap forward.
In previous experiments, it was shown that transplantation of intraspinal neurons derived from human teratoma cell lines improves dysfunction and prolongs the survival of G93A SOD1 transgenic mice. In addition, the life span of G93A SOD1 mice was extended by intravenous administration of human cord blood. Cells were shown to migrate to the spinal cord and brain parenchyma and survive 10-12 weeks after infusion. They showed a beneficial effect, although only a small number of transplanted cells expressed neural antigens. In another study, Sertoli cells that are not neural stem cells were implanted in the spinal cells of SOD1 transgenic mice and, as has been shown, provide temporary protection for motor neurons in their vicinity. However, viable Sertoli cells were not present at the time when the animals died.
Preliminary tests with autologous hematopoietic stem cells have been reported in humans. In one of the peripheral blood-purified CD34 + cells, 3 patients with ALS were injected intrathecally. No adverse events were reported after 6–12 months, but clinical efficacy was not reported. In another case, 7 patients received transplantation of transplantation of autologous stem cells derived from bone marrow. Minor postoperative side effects were temporary, but muscle strength continued to decline. However, after 3 months, researchers reported a tendency to slow the decline in the proximal muscle groups of the lower limb in 4 patients and a moderate increase in strength in 2 patients. A lack of placebo control and longer follow-up exclude the possibility of evaluating the effectiveness of this study, and none of them was made by the researchers.
Stem cell research: ethics, economics, politics and public health
The ethics of conducting research at an early stage of stem cell research has been questioned, stressing the risk of premature human trials. Reports on stem cell transplants conducted in China without expert assessment of objective data for each patient before, immediately after and at specific long-term points after transplantation do not provide sufficient scientific data to demonstrate that treatment is safe and effective.
“It is imperative that scientists and clinicians be careful, plan hard research and, most importantly, focus on key laboratory experiments that will provide answers to many of the problems that still face this therapeutic approach,” writes Lucy Broin, candidate Science, Director of Science and Vice President of the Association of ALS. "In order for this therapy to be safe and have potential in the clinic, it is important that the relevant studies are linked in order to learn more about the properties and complexities of various stem cells."
In response to restrictions on the type of stem cell research that can be performed using federal funds, the American Academy of Neurology and the American Neurological Association — 2 leading professional neurological organizations in the United States — also went on record, expressing the belief that both embryonic and adult stem cell research should be carried out strictly and under scrutiny, respecting the interests of its members and the public regarding important ethical principles and prices awns related to research with human embryonic stem cells.
Scientific problems 2 times. First, since the realistic likelihood of success for any particular research effort is low, parallel research in different directions is necessary to accelerate the development of the field. The essence of the study - trial and error, which act by identifying inefficient areas and thereby focusing on those that promise. As a rule, a long time between the initiation of research and successful treatment in clinical applications. Therefore, any delay in identifying potentially effective therapeutic interventions leads to a delay in the treatment of patients with such diseases. Secondly, the exclusion of specific types of research from federal funding may lead to the exclusion of this study from federal supervision and protection, which may lead to its migration abroad. This can be detrimental to individual patients and the wider community of patients, clinicians and scientists.
In November 2004, Californian citizens approved a referendum measure to issue bonds to finance stem cell research, including embryonic stem cell research of $ 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 funding initiatives for state stem cell research to fill the federal funding gap. This is partly due to the desire to remain at the forefront of medical research and to prevent brain drain in the direction of states that provide an economic environment that is more conducive to advanced research. The California Pulsation Initiative is expected to accelerate stem cell research throughout the country.
Conclusion
Stem cell research promises patients with ALS and may lead to the development of new treatments to slow the progression of the disease. This hope must be mitigated with caution due to the early stages of stem cell research in general and, in particular, in ALS and due to the record limitations of the effectiveness of all pharmacological interventions in transgenic mouse and sporadic human ALS. Careful attention to the ethics and scientific rigor of future stem cell research should be supported by clinicians, scientists, and participating patients.
