Stem Cell Research Targets Cerebral Palsy

ScienceDaily (Aug. 18, 2004) — Natural chemicals that assist healing may one day help transplanted adult stem cells integrate into an injured brain, helping children with cerebral palsy recover lost function, according to researchers at the Medical College of Georgia.
"We know that we can get stem cells into the brain and they will turn into brain cells but we really don't know how well they work," says Dr. James E. Carroll, chief of the MCG Section of Pediatric Neurology. "The cells probably do form synapses," he says of connections brain cells make so they can communicate. "But the question is: Will all this integrate into improved function?"

Dr. Carroll is principal investigator on a new grant from the American Heart Association and an existing grant from the National Institutes of Health that are using an animal model of cerebral palsy to identify the most effective way to transplant stem cells and possibly answer that question.

With this latest grant, Dr. Carroll, who also treats patients with cerebral palsy, wants to determine whether transplanted stem cells work best when the cells are injected directly into the brain along with these natural chemicals, called chemokines.

Chemokines are growth factors that attract white blood cells and are quickly summoned to the site of an injury, such as a brain injury that occurs in cerebral palsy. More recently, researchers have found that chemokines also seem to attract stem cells to an injury site. However, at least in an animal model of cerebral palsy, the healing chemicals are present for only a few days after injury, Dr. Carroll has shown.

"Chemokines are produced normally, naturally and briefly after a brain injury of some type as part of the healing process," Dr. Carroll says. "But probably there are not enough of them produced and they are not produced long enough to do what we want to do. So we are working on ways to get additional factor into the brain to promote the integration of new cells long after the injury has occurred."

When he began his studies several years ago, Dr. Carroll was putting stem cells from donor mice into the circulation of an animal model of cerebral palsy. Preliminary work had shown that stem cells migrated to the injury site, but his studies showed too few cells were making the journey. The two-year grant from the American Heart Association, will enable to him to explore whether a direct injection into the brain can help increase the number of cells where they are needed and if the extra chemokines help them become part of a better-functioning brain.

He'll try several direct approaches including injecting chemokines into the injury site first and stem cells second and taking the technically-easier route of injecting both at the same time. To enable this approach, Dr. Carroll will use a virus' ability to infect a cell to get chemokines inside stem cells before they are injected.

Although stem cells are immature cells coveted for their potential to become many different types of cells, donated stem cells may trigger an immune response, much like a transplanted organ. So Dr. Carroll also will compare the success of transplants that include the immunosuppressive agent, cyclosporine-A, to those that don't.

He'll also look at the bottom line: whether the motor skills of the animal model are improved following the transplant.

Since he began his studies of stem cell transplants, parents nationwide have asked when the technique will be available to help children. "I tell them we are working hard and making progress, but it is slow and there may be clinical trials in several years," Dr. Carroll says. Although he thinks there is potential for stem cell therapy to one day help restore function lost to the group of disorders known as cerebral palsy, many unanswered questions remain. One concern is whether these proliferating young cells might cause tumors. Also, cerebral palsy is not a single problem, but a complex disease in which virtually all brain cell types could need repair.

He noted that there is much parents and caregivers already do for children with cerebral palsy, including physical therapy along with botox injections and baclofen pumps to reduce debilitating spasticity that comes from confused communication to the muscles about whether they should relax or contract.

Cerebral palsy, which affects about 500,000 people in the United States, is defined as brain damage that occurs before or during birth. The number of people with the disorder has increased over the last 30 years as more premature babies survive. Its effects run the gamut, from barely detectable to devastating loss of motor control. The causes are diverse as well, including everything from oxygen deprivation during birth to prenatal infections.

Potential of Stem Cell Treatments for Autism

Autism is a complex brain developmental disorder that is characterised by impaired social interactions, communication difficulties, obsessive attachment to routines and repetition, and often an extreme dislike of certain sounds, textures and tastes. Autism usually surfaces in the first three years of life and may vary in severity from mild to disabling. Depending on degree of severity, some children with autism may develop into independent adults with full time employment and self-sufficiency; however this is seldom the case (2). There is no known single cause but abnormalities in brain function are generally attributed to environmental, immunological and neurological factors.


Social costs
It is reported as one of the fastest-growing developmental disabilities in the US, with diagnoses having increased by staggering proportions in the last decade (2). An estimated 1.5 million children and adults in the U.S. currently (as at 2007) have some form of autism (2). Presenting these statistics another way; autism spectrum disorders are believed to affect approximately 1 in 166 children (1).

Children with autism suffer from two major conditions: Hypoperfusion and Immune Dysregulation

Hypoperfusion of the brain in autism

Children with autism have shown impaired blood flow (hypoperfusion) to the brain. Hypoperfusion may contribute to functional defects not only by inducing hypoxia (an oxygen deficit that prevents normal brain function) but also by allowing for abnormal metabolite or neurotransmitter accumulation. Hypothetically, if perfusion can be improved through the revitalisation of blood vessels (angiogenesis), then this should also allow for metabolite clearance and restoration of functionality.

Immune dysregulation in autism
Successful neurodevelopment is contingent upon a normal balanced immune response. Children with autism have immune systems that do not function normally; instead an autoimmune response of the nervous system appears to prevail (3). Astrocytes (supportive brain cells) that normally play a critical role in regulating perfusion [reviewed in 1] and protection against central nervous system infection, have the potential to cause damage to the host when functioning in an aberrant (i.e. auto-immune) manner. Autistic children often have continually suppressed immune systems and chronic inflammation. Immune dysregulation is very apparent in gastrointestinal health - most autistics experience symptoms ranging from diarrhea, gas, and bloating to intestinal lesions and inflammation of their gastrointestinal system (3,4).

Autism treatments
At this time there is no universally-accepted therapy or cure for autism. Current approaches are either behavioural, medical (treatment of anxiety and depression), nutritional (restriction of allergy-associated dietary components/ supplementation of minerals and vitamins/antioxidant therapy) or a combination of these. Research has increasingly focused on the connections between the immune system and the nervous system (4) yet to date no approach has been successful in correcting immune dysregulation/chronic inflammation in autism.

Rationale for using Stem Cells to treat autism
The administration of CD34+ umbilical cord cells and mesenchymal cells are proposed as novel treatments for the two pathologies associated with autism – hypoperfusion to the brain and immune dysregulation (1). Using these two kinds of stem cells together may potentially heal both the brain and the gut (3,4).

Treatment of hypoperfusion defect with umbilical cord blood CD34+ stem cells
Angiogenesis - the formation of collateral blood vessels - is believed to be fundamental in neurological recovery. A promising method of increasing angiogenesis into damaged areas is by administration of CD34+ stem cells [reviewed in 1]. Umbilical cord blood has highly active CD34+ cells that, following injection into a patient, should induce angiogenesis in areas of cerebral hypoperfusion. Consequently improved blood flow and oxygen to the brain should also improve nervous system functioning.
Safety: Allogeneic cord blood CD34+ cells are needed if this therapy is to be made available for widespread use because few, if any, patients will have access to autologous cord blood. Safety concerns regarding allogeneic CD34+ cells centre on fears of graft / host reactions. It is believed that allogeneic cord blood cells can not be used without immune suppression however Riordan et al (6) have recently published an account of the feasibility of cord blood cells administration in absence of immune suppression. Also, there are reports of stem cell treatments where no immune suppression was used in over 500 patients without a single one suffering graft vs. host disease [reviewed in 1].

Immune modulation by mesenchymal stem cells
The treatment of immune dysregulation in autism is expected to profoundly influence neurological function. The ability of mesenchymal stem cells to suppress pathological immune responses (e.g. inflammation) and to stimulate haematopoiesis (blood cell regeneration) leads to the possibility that these cells may also be useful for treatment of the defect in T cell numbers associated with autism(3).
Safety: The review by Ichim et al (1) suggests that allogeneic mesenchymal stem cells administered to suppress inflammation may be used without fear of immune-mediated rejection.

Practical clinical entry
The following passage is quoted directly from the authors’ proposal in ‘Stem Cell Therapy for Autism’(1) and outlines their suggestions for clinical trials : “We propose a Phase I/II study investigating a combination of cord blood expanded CD34+ cells together with mesenchymal stem cells for the treatment of autism and clinical manifestations of inflammatory intestinal disease. One of the authors (*Fabio Solano) has utilized both CD34+ and mesenchymal stem cells clinically for treatment of various diseases. In some case reports, the combination of CD34+ and mesenchymal stem cells was noted to induce synergistic effects in neurological diseases, although the numbers of patients are far too low to draw any conclusions. We propose to conduct this study based on the previous experiences of our group in this field, as well as numerous other groups that have generated anecdotal evidence of stem cell therapy for autism but have not published in conventional journals. We believe that through development of a potent clinical study with appropriate endpoints, much will be learned about the pathophysiology of autism regardless of trial outcome.”

Cautionary arguments
While the rationale for using stem cells to treat autism is indeed sound, many proponents of stem cell treatment for autism (6,7,8,9) are in agreement that clinical trials with sufficient patient numbers are needed to assess treatment efficacy. When patients and their families consider new treatments, the proposals need to be interpreted in a discerning manner that can be balanced with scientific evidence.

REFERENCES
1. Review: Stem Cell Therapy for Autism Thomas Ichim, Fabio Solano, Eduardo Glenn, Frank Morales, Leonard Smith, George Zabrecky, Neil H Riordan Journal of Translational Medicine June 2007, 5:30 http://www.translational-medicine.com/content/5/1/30
2. Alliance for stem cell research www.curesforcalifornia.com
3. The immune response in autism: a new frontier for autism research Paul Ashwood, Sharifia Wills, Judy vd Water Journal of Leukocyte Biology. 80:1–15; 2006
4. The Stem Cell and Autism Connection www.bodyecology.com
5. Autism www.stemcelltherapies.org
6. Cord blood in regenerative medicine: do we need immune suppression? Riordan N, Chan K, Marleau A, Ichim T. Journal of Translational Medicine. Jan 2007 5:8
7. www.autismvox.com/another-autism-treatment-stem-cell-therapy Kristina Chew, July 2007
8. www.cellmedicine.com (publication is equivalent to Review: Stem Cell Therapy for Autism Ichim et al.)
9. Osiris www.osiris.com

Hospitals are More Hazardous in July

July 1 marks the beginning of the academic year for medical students, when the annual influx of new interns begins at hospitals. Many experts believe that July is therefore the riskiest time of the year for hospital patients, who are susceptible to the mistakes of new medical staff.

A study of this trend concluded that “the July medical-training period is associated with between 1,500 and 2,750 accelerated deaths every year.”

Medical students must deal with their new responsibility of working with patients, and acclimate to the nuances of their assigned hospital and a demanding work schedule. Overworked interns’ long hours and extended shifts may also be responsible for the high rate of accidents that occur when they join a medical staff.

Sources:

* Finding Dulcinea July 2, 2008

Resveratrol, Found In Red Wine, Wards Off Effects Of Age On Heart, Bones, Eyes And Muscle

Scientists have found that the compound resveratrol -- found in red wine and grape skin -- slows age-related deterioration and functional decline of mice on a standard diet, but does not increase longevity when started at middle age.

This study, conducted and supported in part by the National Institute on Aging (NIA), part of the National Institutes of Health, is a follow-up to 2006 findings that resveratrol improves health and longevity of overweight, aged mice. The report confirms previous results suggesting the compound, found naturally in foods like grapes and nuts, may mimic, in mice, some of the effects of dietary or calorie restriction, the most effective and reproducible way found to date to alleviate age-associated disease in mammals.

The findings, published July 3, 2008, in Cell Metabolism, may increase interest in resveratrol as a possible intervention for age-related declines, said NIA scientists. The authors emphasized, however, that their findings are based on research in mice, not in humans, and have no immediate and direct application to people, whose health is influenced by a variety of factors beyond those which may be represented in the animal models.

The study is a collaborative effort between the laboratories of Rafael de Cabo, Ph.D., of the Laboratory of Experimental Gerontology at the NIA; David A. Sinclair, Ph.D., of the Glenn Laboratories for Molecular Biology of Aging at Harvard Medical School; and an international group of researchers. The investigators compared mice fed a standard diet, a high-calorie diet, or an every-other-day feeding regimen with or without high- or low-dose resveratrol to study the impact of resveratrol on aging and health. In previous studies, different forms of dietary restriction, including every-other-day feeding, have been shown to improve markers of health.

"Research is attempting to understand the process of aging and to determine how interventions can influence this process. Dietary restriction has well-documented health benefits in mammals, and the study of possible mimetics of it, such as resveratrol, are of great interest," said NIA Director Richard J. Hodes, M.D. "Resveratrol has produced significant effects in animal models, now including mice, where it mimics some, but not all, consequences of caloric restriction. Its effects in humans remain to be studied."

A major finding of the study reported today is that resveratrol prevented age-related and obesity-related cardiovascular functional decline in the mice as determined by several parameters. Total cholesterol was significantly reduced in 22-month-old non-obese mice after 10 months of resveratrol treatment, although triglyceride levels had only a slight, non-significant trend toward a decrease. Further, the aortas of 18-month-old obese and non-obese mice treated with resveratrol functioned significantly better than untreated mice. Resveratrol also moderated inflammation in the heart.

In addition to cardiovascular function, the scientists found resveratrol to have a variety of positive effects on other age-related problems in mice:

* Treated mice tended to have better bone health, as measured by thickness, volume, mineral content and density, and bending stiffness compared to the non-treated control group.
* At 30 months of age, resveratrol-treated mice were found to have reduced cataract formation, a condition found to increase with age in control-group mice.
* Resveratrol enhanced balance and motor coordination in aged animals. Scientists found significant improvement in performance at 21 and 24 months versus 15 months in the resveratrol-treated mice but not in the untreated mice.
* Resveratrol partially mimicked the effects of dietary restriction on the gene expression profiles of liver, skeletal muscle and adipose (fatty) tissue in mice.
* Along with determining the effect of resveratrol on the health of mice, scientists also studied the effect of resveratrol on longevity.

"We found that while quality of life improved with resveratrol, the compound did not significantly affect overall survival or maximum lifespan for mice on a standard diet, compared to mice on the same diet without resveratrol," said de Cabo.

Resveratrol did not have a significant effect on lifespan in animals fed standard chow, suggesting that the intervention did not affect all aspects of the basic aging process. Mice on a high-calorie diet without resveratrol lived the shortest length of time and mice on an every-other-day regimen lived the longest, regardless of resveratrol treatment. However, for mice on a high-calorie diet, mean and maximum lifespan increased for mice on resveratrol when compared with the control mice.

Researchers found that resveratrol's effects on longevity could be completely uncoupled from changes in body weight, meaning that mice on a high-calorie diet with resveratrol did not necessarily lose weight but did experience a longer (and healthier) life than mice on the same high-calorie diet not taking resveratrol. They speculate that improved cardiovascular health and reduced fatty changes in the liver may have contributed to the increased lifespan of resveratrol-treated mice.

Researchers still have much to learn before resveratrol can be recommended for human use. Basic questions of safety and biological effect in humans remain to be studied experimentally.

"We are learning a great deal about how resveratrol affects the health and survival of mammals," said Sinclair. "Continued study of calorie restriction mimetics such as resveratrol may eventually point the way to new medicines to treat diseases of aging."

In addition to scientists from the NIA and Harvard Medical School, researchers from the following institutions collaborated in this study: New York Medical College, Valhalla, N.Y.; University of Michigan, Ann Arbor; University of Sydney in Australia; Thomas Jefferson University, Philadelphia; University of California, San Diego, La Jolla; Hospital for Special Surgery, New York, N.Y.; University of Cincinnati, Ohio; University of Texas Health Science Center at San Antonio and Audie Murphy VA Hospital, San Antonio, Texas; Universidad Pablo de Olavide, Sevilla, Spain; Pennington Biomedical Research Center, Baton Rouge, La.; University of Washington, Seattle; and Sirtris Pharmaceuticals of Cambridge, Mass., a company founded by Harvard University co-lead author Sinclair.

De Cabo is a scientist in the NIA's Intramural Research Program. In addition, the research was funded by grants from the NIA, the primary supporter of the work, as well as grants from the National Institute of General Medical Sciences; the National Heart, Lung, and Blood Institute; the National Institute of Child Health and Human Development; the National Eye Institute; and the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the NIH. The Ellison Medical Research Foundation, the American Heart Association, the Australian and Spanish governments and Paul F. Glenn and The Paul F. Glenn Laboratories for the Biological Mechanisms of Aging also provided support to members of the research team.
Adapted from materials provided by NIH/National Institute on Aging, via EurekAlert!, a service of AAAS.

Toxic Metals: The Reason You Still Feel Sick

Dr, Kaayla Daniel and Dr. Galen Knight have observed that even when people follow healthy dietary guidelines, they can still have serious health problems. They may digest their food poorly, experience digestive distress, or be generally sickly.

One reason may be toxic metals. Mercury, aluminum, cadmium, arsenic, lead, nickel, and other metal poisons flood the environment and invade your body. Toxic metals can cause or contribute to a long list of diseases including Alzheimer’s disease, Parkinson’s disease, and other brain and neurological disorders. While the medical establishment recognizes the acute toxicity that comes from high levels of metals in your body, far more people suffer the adverse effects of low-level, chronic exposure.

But you can reduce your exposure to dangerous environmental metals by:

* Using glass, cast iron, carbon steel, titanium, and enamel cookware; aluminum and teflon are well known for their toxic dangers, and stainless steel can expose you to carcinogenic nickel

* Minimizing consumption of restaurant food; restaurants are required to use stainless steel pots and vats

* Avoiding stainless steel thermoses; the glass lined kind are best

* Not using cosmetics with aluminum bases, mineral powders that contain bismuth, and aluminum-laden antiperspirants

* Staying away from vaccinations that inject mercury or aluminum directly into your bloodstream

* Avoiding dental amalgam fillings

Other ways to protect yourself include a healthy diet, and the use of food grade diatomaceous earth. More information about this subject will be discussed in my Inner Circle interview with Dr. Kaayla Daniel, coming soon to Mercola.com.


Sources:

* Mad as a Hatter -- How to Avoid Toxic Metals and Clear Them From the Body (PDF)

Swimming the Amazon: 3,274 Miles on the World's Deadliest River

Last year on April 8th, Slovenian marathon swimmer Martin Strel became the first man to swim the entire length of the Amazon River. He swam 3,274 miles from the headwaters in Peru to the Brazilian port city of Belém.

The task took him 66 days with a support crew of near twenty people following him in a boat for protection.

Strel had already swum the Danube, the Mississippi, and the Yangtze. In 1997, he became the first to swim non-stop from Africa to Europe, which he did in 29 hours, 36 minutes, and 57 seconds. Seven previous swimmers had attempted -- and failed -- that swim before Strel.

When Strel reached the finish line at Belém, he had to be helped to his feet and ushered into a wheelchair. His blood pressure was at heart-attack levels and his entire body was full of subcutaneous larvae.

You can click the link below the read a fascinating interview with Strel.


Sources:

* Four Hour Work Week July 1, 2008

How Broccoli Fights Cancer

Just a few additional portions of broccoli each week could protect men from prostate cancer. Researchers believe a substance called isothiocyanate in the broccoli sparks hundreds of genetic changes, activating some genes that fight cancer and switching off others that fuel tumors.

Prostate cancer kills more men than any other kind except for lung cancer. Each year, 680,000 men worldwide are diagnosed with the disease and about 220,000 will die from it.

The benefit derived from broccoli would likely also be available from other cruciferous vegetables that contain isothiocyanate, including Brussels sprouts, cauliflower, cabbage, arugula, watercress and horseradish.


Sources:

* Reuters July 1, 2008

How to Shop for Organic Foods Without Breaking Your Budget

Pesticide and hormone-free products often have a premium price tag, meaning that organic food can seem like a luxury for anyone on a tight budget. But there are ways to buy good food without draining your bank account.

Craig Minowa, environmental scientist with the Organic Consumers Association, offers these tips:

* Learn to buy big -- Many health-food stores have bulk sections, and if you fill a bag with organic cereal, you may end up paying less for it than you would for the nonorganic variety
* Form a buying club -- If a bunch of people pool their grocery lists, they can often special-order directly with the store

Sarah Bratnober, communications director at the Organic Valley Family of Farms, advises:

* Follow the 80/20 rule -- 80 percent of the benefits come from 20 percent of the purchases; think about what your family eats the most of, and make sure that those products are organic

Barbara Houmann, spokeswoman for the Organic Trade Association, says:

* Buy fruits and vegetables in season -- you’ll save money by focusing on what's easily available

If you do manage to get more organic into your diet, you won't regret it. Organic produce isn't just healthy and better for the environment, it tastes better, too.


Sources:

* Newsweek June 14, 2007

Vaccinations at Some Clinics Suspended Following Child's Death

All Genesis Medical Center Pediatric Clinics have suspended their use of childhood vaccines after a baby received routine vaccinations, then died several hours later at home. Genesis Health Group says that it is suspending pediatric vaccinations merely as a precaution until the cause of the baby's death can be determined.

The seemingly healthy baby boy was brought in for a "well baby" visit that includes routine vaccinations for pneumonia, diphtheria, pertussis (whooping cough) and tetanus. Later that night, his parents found him dead with no obvious cause for his death.

Genesis sent the batch of vaccines the boy received to the FDA and to the makers of the vaccines for testing. This is the first time Genesis has ever suspended pediatric vaccinations at its clinics.


Sources:

* WQAD July 2, 2008

Bird Flu Vaccine Kills the Homeless

Three Polish doctors and six nurses face criminal prosecution after a number of homeless people died following medical trials for a vaccine to the H5N1 bird-flu virus.

The medical staff are being investigated over medical trials conducted on as many as 350 homeless and poor people last year. Authorities claim that the alleged victims received money to be tested with what they thought was a conventional flu vaccine, but was actually an anti bird-flu drug.

The director of the homeless center in the area said that 21 people from his center died this year, a figure well above the average of about eight.

The suspects said that the all those involved knew that the trial involved an anti-H5N1 drug and willingly participated.


Sources:

* The Telegraph July 3, 2008