Stems of Hope for Treating Incurable Diseases
Stems of Hope for Treating Incurable Diseases
The Future of Things - USA
... as well as to researchers developing stem cells techniques for treatment of other diseases. Multiple Sclerosis (MS) and Amytrophic Lateral Sclerosis ...
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Stems of Hope for Treating Incurable DiseasesThursday, December 27, 2007 - Einat Rotman
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Two Professors at the Hadassah University Hospital in Jerusalem have succeeded in improving the condition of MS and ALS patients by using stem cells transplants. The researchers extracted stem cells from each patient's bone marrow, cultured them, and then injected them into the patients' spine. The encouraging results of this small clinical study may give hope to those who suffer from these incurable diseases, as well as to researchers developing stem cells techniques for treatment of other diseases.
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Multiple Sclerosis (MS) and Amytrophic Lateral Sclerosis (ALS) are diseases related to the nervous system that currently do not have a cure. MS is the most common neurodegenerative disease. It is a chronic autoimmune inflammatory disease in which an individual’s immune system attacks the central nervous system (CNS), gradually destroying the myelin layers that surround and electrically insulate specific parts of neurons (nerve cells). The myelin layers are important because they enable neural impulses to propagate along the neurons at a high speed. Although the CNS is able to recruit stem cells of remyelinating cells (named oligodendrocytes), these cells are somehow inhibited in repeatedly attacked areas. For this reason, repeated attacks of the immune system can lead to severe impairment of the neural signals and to scarring of the damaged portion of the neuron. MS symptoms depend on the location of the multiple lesions’ occurrence in the CNS. These neurological deficits are progressively accumulated, leading to functional sphincter, sensor, and motor deficiencies. The patient's vision and balance are also damaged.
Amyotrophic Lateral Sclerosis (ALS, or Lou Gehrig's Disease) is one of the most common neuromuscular diseases worldwide. It is a progressive, usually fatal, neurodegenerative disease caused by the degeneration of motor neurons, the nerve cells in the CNS that control voluntary muscle movement. As motor neurons degenerate and die, neural signaling to the muscles ceases, resulting in muscle weakness, atrophy, and twitches throughout the body. Patients may ultimately lose their ability to control all voluntary movements except of the eyes. The cause of ALS is not known, and no cure has been found for the disease.
Mesenchymal stem cells are found in the bone marrow and are multipotent - they can differentiate into a variety of cell types, including CNS cells (such as oligodendrocyte-like cells), if cultured in the right conditions. They have also been shown to be able to migrate into the brain. These features make autologous (self) bone marrow transplants, on which the treatment developed at Hadassah University Hospital was based, a possible method for treating various neural diseases.
Professor Dmitrius Karussis, a Senior Neurologist at Hadassah and the Director of the new Multiple Sclerosis Center, worked in collaboration with the University of Athens, and with Professor Shimon Slavin, the Former Director of the Department of Bone Marrow Transplantation (BMT) and the BMT Laboratory at Hadassah. The scientists successfully isolated mesenchymal stem cells from the patients' bone marrow, cultured them under special conditions, and generated over 50 million stem cells within two months. The mesenchymal cells were marked so that the scientists could track them and verify that they reach the intended destination in the patient's body. The cells were then transplanted by a lumbar injection into the patient's spinal cord (into the spinal fluid of the CNS). Each patient served as his/her own bone marrow donor.
According to Professor Karussis, the effectiveness of stem cells was initially studied in laboratory animals, where it was found that stem cells from bone marrow can reduce cerebral damage and improve the animal's functioning. During the past two years Professor Karussis has conducted clinical trials with 9 patients suffering from multiple sclerosis and with 16 patients suffering from ALS. "Most of the patients who underwent this process report an improvement in their condition," Professor Karussis said. The purpose of this initial trial was to identify undesired effects of the procedure. So far, no major safety issues have been encountered. However, a controlled larger scale clinical trial should be conducted in order to establish the safety and efficacy of the treatment.
Even more hope for MS - using
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Directed to differentiate into specific cell types, stem cells offer the possibility of a renewable source of replacement cells and tissues to treat a variety of diseases. A number of stem cell therapies already exist, particularly bone marrow transplants that are used to treat leukemia. Medical researchers expect stem cell technologies to treat a wider variety of diseases in the future, including cancer, Parkinson's and Alzheimer's diseases, spinal cord injuries, strokes, heart disease, diabetes and arthritis. The clinical trial in Hadassa is supporting this approach, giving patients suffering from various diseases a hope for effective treatments or even cures.
TFOT recently published a comprehensive article about stem cells, covering their biological origin, applications and ethical issues. We also covered another stem cell therapy research that demonstrated the differentiation of human stem cells into heart muscle cells, and a different approach for the creation of tissues, which was demonstrated by an artificial vascular system developed in Cornell University.
Hadassah’s press release of the experimental stem cell treatment is available here.
Professor Dimitrios Karussis
Professor Dimitrios Karussis
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Snorting a Brain Chemical Could Replace SleepBy Alexis Madrigal 12.28.07 | 12:00 AM
In what sounds like a dream for millions of tired coffee drinkers, Darpa-funded scientists might have found a drug that will eliminate sleepiness.
A nasal spray containing a naturally occurring brain hormone called orexin A reversed the effects of sleep deprivation in monkeys, allowing them to perform like well-rested monkeys on cognitive tests. The discovery's first application will probably be in treatment of the severe sleep disorder narcolepsy.
The treatment is "a totally new route for increasing arousal, and the new study shows it to be relatively benign," said Jerome Siegel, a professor of psychiatry at UCLA and a co-author of the paper. "It reduces sleepiness without causing edginess."
Orexin A is a promising candidate to become a "sleep replacement" drug. For decades, stimulants have been used to combat sleepiness, but they can be addictive and often have side effects, including raising blood pressure or causing mood swings. The military, for example, administers amphetamines to pilots flying long distances, and has funded research into new drugs like the stimulant modafinil (.pdf) and orexin A in an effort to help troops stay awake with the fewest side effects.
The monkeys were deprived of sleep for 30 to 36 hours and then given either orexin A or a saline placebo before taking standard cognitive tests. The monkeys given orexin A in a nasal spray scored about the same as alert monkeys, while the saline-control group was severely impaired.
The study, published in the Dec. 26 edition of The Journal of Neuroscience, found orexin A not only restored monkeys' cognitive abilities but made their brains look "awake" in PET scans.
Siegel said that orexin A is unique in that it only had an impact on sleepy monkeys, not alert ones, and that it is "specific in reversing the effects of sleepiness" without other impacts on the brain.
Such a product could be widely desired by the more than 70 percent of Americans who the National Sleep Foundation estimates get less than the generally recommended eight hours of sleep per night (.pdf).
The research follows the discovery by Siegel that the absence of orexin A appears to cause narcolepsy. That finding pointed to a major role for the peptide's absence in causing sleepiness. It stood to reason that if the deficit of orexin A makes people sleepy, adding it back into the brain would reduce the effects, said Siegel.
"What we've been doing so far is increasing arousal without dealing with the underlying problem," he said. "If the underlying deficit is a loss of orexin, and it clearly is, then the best treatment would be orexin."
Dr. Michael Twery, director of the National Center on Sleep Disorders Research, said that while research into drugs for sleepiness is "very interesting," he cautioned that the long-term consequences of not sleeping were not well-known.
Both Twery and Siegel noted that it is unclear whether or not treating the brain chemistry behind sleepiness would alleviate the other problems associated with sleep deprivation.
"New research indicates that not getting enough sleep is associated with increased risk of cardiovascular disease and metabolic disorders," said Twery.
Still, Siegel said that Americans already recognize that sleepiness is a problem and have long treated it with a variety of stimulants.
"We have to realize that we are already living in a society where we are already self-medicating with caffeine," he said.
He also said that modafinil, which is marketed as Provigil by Cephalon and Alertec in Canada, has become widely used by healthy individuals for managing sleepiness.
"We have these other precedents, and it's not clear that you can't use orexin A temporarily to reduce sleep," said Siegel. "On the other hand, you'd have to be a fool to advocate taking this and reducing sleep as much as possible."
Sleep advocates probably won't have to worry about orexin A reaching drugstore shelves for many years. Any commercial treatment using the substance would need approval from the Food and Drug Administration, which can take more than a decade.
A nasal spray of a key brain hormone cures sleepiness in sleep-deprived monkeys. With no apparent side effects, the hormone might be a promising sleep-replacement drug.
Over the last months, thanks to the traffic growth of SharpBrains.com (over 100,000 unique visitors per month these days, THANK YOU for visiting today and please come back!), a number of proactive book agents, publishers and authors have contacted us to inform us of their latest brain-related books. We have taken a look at many books, wrote reviews of The Dana Guide to Brain Health book review and Best of the Brain from Scientific American, and interviewed scientists such as Judith Beck, Robert Emmons and James Zull.
Now we are launching a new Author Speaks Series to provide a platform for leading scientists and experts writing high-quality brain-related books to reach a wide audience. We are honored to start the series with an article by Larry McCleary, M.D, former acting Chief of Pediatric Neurosurgery at Denver Children's Hospital, and author of The Brain Trust Program: A Scientifically Based Three-Part Plan to Improve Memory, Elevate Mood, Enhance Attention, Alleviate Migraine and Menopausal Symptoms, and Boost Mental Energy (Perigee Trade, 2007).
Without further ado, let's enjoy Dr. McCleary's article:
Brain Evolution and Why it is Meaningful Today to Improve Our Brain Health
You may feel overwhelmed by the stream of seemingly contradictory suggestions regarding the best way to maintain mental clarity as you age. Based on an analysis of seminal factors in the development of modern brain anatomy, I believe it is possible to make some very compelling recommendations for growing big brains, enhancing their function, and making them resistant to the aging process. These may be loosely categorized as factors pertaining to the mental or physical attributes of the brain. Although they are not truly independent entities, such a conceptualization provides a basis for the generation of brain healthy prescriptions. Diet, physical exercise, and stress reduction enhance neuronal resilience. Sleep and mental stimulation are vital for cognitive ability, learning, and memory.
Diet: Follow a modern shore-based/marine diet including seafood in its most general sense, non-starchy vegetables of all colors, berries, and eggs. Other sources of lean protein containing long-chain omega 3 fatty acids such as free range beef, chicken, bison, or elk are nutritious alternatives.
Physical exercise (Think ‘fight or flight’ activity.): Include all types. Aerobic activities such as swimming, bicycling, walking, or hiking for promotion of vascular health and weight control; resistance training for promotion of neurotrophic factors, naturally occurring compounds that make brain cells more resistant to aging, such as IGF-1 (Insulin-like growth factor-1) and BDNF (Brain-derived neurotrophic factor); and balance, coordination, and agility training such as ping-pong, balance beam, trampoline, and jumping rope to enhance cognitive speed and motor skills.
Stress Control: From an evolutionary perspective, stressors (such as meeting a cave bear) and intense physical activity (running or fighting) were brief in duration and usually occurred together. Modern stressors (psychological or emotional stress) tend to be unremitting and are generally uncoupled from the physical (fight or flight) component, meaning stress develops without any associated physical activity. Such intense physical pursuits are now called exercise. Not surprisingly, exercise is a perfect physiologic antidote for stress due to its beneficial impact on cortisol (the ‘stress’ hormone) and blood pressure and should be incorporated into any program of stress reduction.
Adequate sleep: The body needs rest, but the brain requires sleep. Acute or chronic sleep deprivation causes devastating short and long-term consequences to brain anatomy (synaptic loss) and function (memory and learning difficulties). Off-line information processing and memory consolidation are additional sleep-related benefits.
Mental stimulation: Brain-training, a cognitively challenging lifestyle, novelty, and socialization are vital for the promotion of neuronal plasticity and neurogenesis (the formation of new nerve cells and neuronal connections), the enhancement of specific brain functions such as memory, and the development of cognitive reserve –additional mental processing potential that may be brought online when needed.
The combination of these recommendations, each of which was instrumental in the transformation from primitive to modern nervous systems, provides a template for the most logical approach for enhancing mental function and resisting neurodegeneration as we travel through life.
The Evolutionary Rationale
The human brain clearly has the genetic potential for dramatic expansion. This was illustrated about 1,500,000 years ago. Enlargement from 900 grams to almost 1300 grams required less than a million years to complete – a mere speck on the evolutionary timeline. Why and how it happened are open questions. What remains undisputed are the magnitude of the change and the impact it had on human capabilities. The rapid volumetric explosion primarily involved the frontal lobe region, a portion of the brain that, until recently, was referred to as the ‘silent’ brain because of its relative lack of any discernable functionality. The frontal lobes are now viewed as the ‘conductor of the orchestra’ because they have been recognized as being responsible for articulating the ‘big picture’ and coordinating other brain regions, as needed, to execute the ‘game plan.’ The Prefrontal cortex (PFC), the most anterior portion of the frontal cortex, has dense connections with all the other regions it oversees. It is generally considered the most plastic cortical region because its synapses are continually being torn down and reconfigured in response to real-time experiences. Plasticity allows the brain to ‘think on its feet.’ Expansion of PFC enabled the cognitive preeminence of modern day humans over all non-human primates. The plasticity of the PFC and its massive connectivity with other brain regions rely entirely on the production and maintenance of point-to-point nerve cell connections, or synapses.
In addition to being a thinking machine, the brain is also a flesh and blood organ that must comply with the laws of metabolism and physiology. Insight into both its ‘mental’ and ‘physical’ properties is vital for comprehending key aspects of brain health and function. Much has been written about the facilitation of brain growth by cognitively demanding tasks such as tool use and hunting. However, there is a component of circular reasoning in this argument. For it to participate in such mentally demanding endeavors, the brain would have relied on the prior existence of sophisticated neuronal circuitry. I suggest a nutritional basis for the dramatic cerebral expansion, with enhanced functionality (such as development of tool use and hunting strategy) being the natural responses of a larger, more plastic organ to novelty and environmental challenges. The common link between the evolutionary cerebral expansion and modern brain health/function resides in the massive wiring demands inherent in both processes. This marked amplification in neuronal connectivity is made possible by the enhanced production of synaptic membranes (nerve cell membranes in the regions of points of nerve cell contact).
How was it possible to fuel the production of major increases in neuronal number and synaptic density? This required the concordant expression of genetic potential (likely driven, in part, by the provision of an uninterrupted energy supply) and proper nutritional content - meaning high, sustained caloric and nutrient density. Just as a certain level of fat mass is a prerequisite for expansion of the female body to support a successful pregnancy, a persistent supply of nutrient dense calories is essential for brain expansion. In times of frequent starvation, this was a substantial nutritional demand. To fully appreciate how energetically expensive brains are, consider that modern brains comprise about 2.3% of the body mass, yet consume almost one quarter of the available energy. Newborn brains utilize fully 75% of the body’s energy!
What type of brain-building diet might have been accessible 1.5 million years ago that didn’t require the cognitive demands inherent in hunting? One solution would be a ‘shore-based’ diet. This means foraging for life forms such as mollusks, crustaceans, eggs, spawning fish, frogs, and contiguous plant life readily available along lake shores or river banks. In a warm clime it would have provided a year-round, high quality diet abundant in calories, fat and protein. It also supplied long-chain omega 3 fatty acids (including DHA), the building blocks of electrically active membranes in neurons and photoreceptor cells.
Big brains must also synthesize abundant cholesterol and other components of nerve cell membranes. This requires a water-soluble source of appropriate building blocks. Ketone bodies (acetoacetate and β-hydroxybutyrate) generated naturally from partially burned fat were, and continue to be, an ideal energy source for the brain while simultaneously providing key precursors for synthesis of nerve cell membranes and synapses. These facilitated the anatomic expansion of the brain, which provided the additional neuronal circuitry that made the learning of hunting skills a possibility.
Hence, what was compulsory for explosive brain expansion of the species is as vital today for optimal brain function and plasticity. It is the ongoing ability to produce high levels of the most functional sites of nerve cells – the synaptic membranes. Appropriate assemblies of nerve cells, as determined by their connections (synapses), provide the basis for the functional attributes we enjoy today. Stress reduction, mental stimulation and proper sleep enhance their resistance to the aging process.
---This article was written by Larry McCleary, M.D, for SharpBrains.com's Author Speaks Series. Dr. McCleary (blog) is a former acting Chief of Pediatric Neurosurgery at Denver Children's Hospital. He is trained and has practiced as a pediatric neurosurgeon and has completed post-graduate training in theoretical physics. His scientific publications span the fields of metabolic medicine, tumor immunology, biotechnology and neurological disease. He is the author of The Brain Trust Program: A Scientifically Based Three-Part Plan to Improve Memory, Elevate Mood, Enhance Attention, Alleviate Migraine and Menopausal Symptoms, and Boost Mental Energy (Perigee Trade, 2007).