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