DUARTE, Calif. — City of Hope researchers received approval from the U.S. Food and Drug Administration (FDA) to conduct the first-in-human study of a neural stem cell-based therapy targeting recurrent high-grade gliomas, the most aggressive type of brain tumor. Karen S. Aboody, M.D., associate professor in City of Hope’s Department of Neurosciences, leads the research team that developed this treatment strategy. Jana Portnow, M.D., assistant professor and assistant director of the Brain Tumor Program at City of Hope, is the principal investigator for the clinical trial.

An estimated 22,500 Americans are diagnosed with malignant primary brain tumors annually, and more than 12,900 die each year from the disease. While survival rates vary with the type of brain tumor, median survival for glioblastoma, the most common type of glioma in adults, is only about 15 months. These tumors are highly invasive and ultimately resistant to current methods of treatment such as surgery, radiation and chemotherapy. One significant obstacle to curing brain tumors is the presence of the blood-brain barrier which can prevent chemotherapy agents from entering into the brain and reaching effective concentrations at tumor sites.

“This first-in-human clinical trial of a neural stem cell-based therapy that we developed at City of Hope is an investigational, targeted treatment option for recurrent high-grade glioma patients,” said Aboody. “Furthermore, we envision the eventual development of neural stem cells as a platform technology for targeting multiple therapeutic agents to brain tumors, as well as other metastatic solid tumors inside and outside the brain.”

Aboody and her colleagues were the first to demonstrate in 2000 the inherent propensity of neural stem cells to home in on invasive tumor cells, also known as tropism, even migrating from the opposite side of the brain or across the blood-brain barrier. Aboody’s research team has since harnessed the tumor-tropism of neural stem cells to deliver therapeutic agents to invasive tumor sites, which they demonstrated in laboratory testing. The therapy uses a genetically modified human neural stem cell line, generated by Seung U. Kim, M.D., Ph.D., professor in the Division of Neurology at the University of British Columbia, to deliver a prodrug-activating enzyme (cytosine deaminase) to brain tumor sites. This enzyme converts a relatively nontoxic prodrug (5-Fluorocytosine, 5-FC), which is delivered systemically, into an active cancer-fighting chemotherapeutic (5-Fluorouracil, 5-FU). In effect, this stem cell-mediated strategy achieves production of the chemotherapeutic drug only in the area of the tumor. This investigational treatment concentrates anticancer compounds at tumor sites while minimizing exposure of surrounding healthy tissue.

“This novel tumor-selective treatment has the potential to overcome many obstacles that limit the success of currently available treatments for malignant brain tumors and other invasive cancers,” said Aboody. “Using neural stem cells as delivery vehicles for therapy may allow us to target concentrated therapeutics specifically to tumor sites while reducing the undesirable side effects of current chemotherapy regimens, including toxicity to normally dividing bone marrow, gastrointestinal tract, skin and hair cells.”

The clinical trial will begin accepting patients this summer, with the goal of enrolling 12 to 20 patients with recurrent high-grade gliomas. The modified neural stem cells will be injected during surgery into the wall of the cavity remaining after tumor tissue has been removed. Study patients then receive daily doses of the prodrug 5-FC for one week. Based on Aboody’s laboratory findings, once the 5-FC crosses the blood-brain barrier, the neural stem cells will convert the 5-FC to the active chemotherapy agent, 5-FU, at tumor sites in the brain. The phase I safety trial will assess the maximum tolerated dose of the therapy, and is supported by a grant from the National Cancer Institute, part of the National Institutes of Health.

Dr Denise Houston of Wake Forest University’s Sticht Center on Aging and her colleagues analyzed data from 2,788 healthy participants in the Health, Aging, and Body Composition (Health ABC) study, which was designed to evaluate associations between body composition, long-term health conditions and mobility in older individuals. The subjects, who resided in Memphis and Pittsburgh, had an average age of 74.7 years. Blood samples obtained upon enrollment were analyzed for serum 25-hydroxyvitamin D levels. Lower extremity function, as assessed by tests of walking, balance, endurance and strength, was evaluated at the beginning of the study and at two and four years.

Over 90 percent of the study population was found to consume less vitamin D than the current recommendation. Although physical function decreased on average among all participants over the follow-up period, those who had high vitamin D levels at 75 nanomoles per liter or more at the beginning of the study retained better function, with improved physical performance scores and gait speed across all three time points compared to those whose levels were lowest at less than 50 nanomoles per liter.

The study is one of only a few to examine the longitudinal relationship between vitamin D levels and physical function. “Current dietary recommendations are based primarily on vitamin D’s effects on bone health,” Dr Houston remarked. “It is possible that higher amounts of vitamin D are needed for the preservation of muscle strength and physical function as well as other health conditions. However, clinical trials are needed to definitively determine whether increasing 25-hydroxyvitamin D concentrations through diet or supplements has an effect on these non-traditional outcomes.”

The lead researcher, Simin Nikbin Meydani, is director of the Jean Mayer USDA Human Nutrition Research Center on Aging (HNRCA) at Tufts University in Boston, Mass., and also of the HNRCA’s Nutritional Immunology Laboratory.

The study is part of the “Comprehensive Assessment of Long-Term Effects of Reducing Intake of Energy” trial conducted at the HNRCA. As people age, their immune response generally declines. Calorie restriction has been shown to boost these immune responses in animal models.

In the study, 46 overweight (but not obese) men and women aged 20 to 40 years were required to consume either a 30-percent or 10-percent calorie-restricted diet for six months.

Prior to being randomly assigned to one of the two groups, each volunteer participated in an initial 6-week period during which measures of all baseline study outcomes were obtained. All food was provided to participants.

For the study, the researchers looked at specific biologic markers. A skin test used called DTH (delayed-type hypersensitivity) is a measure of immune response at the whole body level.

The researchers also examined effects of calorie restriction on function of T-cells–a major type of white blood cell–and other factors on the volunteer’s immune system.

DTH and T-cell response indicate the strength of cell-mediated immunity. One positive was that DTH and T-cell proliferative response were significantly increased in both calorie-restrained groups.

These results show for the first time that short-term calorie restriction for six months in humans improves the function of T-cells.

High-carbohydrate diets increase the levels of blood glucose and of harmful blood fats known as triglycerides while reducing levels of protective HDL or “good” cholesterol, thereby increasing heart disease risk, according to background information in the article. However, not all carbohydrates have the same effect on blood glucose levels. The glycemic index is a measure of how much a food raises blood glucose levels compared with the same amount of glucose or white bread. A related measure, the glycemic load, is calculated based on the glycemic index of a given food and also on the total amount of carbohydrates it contains.

Sabina Sieri, Ph.D., of Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy, and colleagues studied 47,749 Italian adults-15,171 men and 32,578 women-who completed dietary questionnaires. Based on their responses, the researchers calculated their overall carbohydrate intakes as well as the average glycemic index of the foods they consumed and the glycemic loads of their diets. During a median (midpoint) of 7.9 years of follow-up, 463 participants (158 women and 305 men) developed coronary heart disease.

The one-fourth of women who consumed the most carbohydrates overall had approximately twice the risk of heart disease as the one-fourth who consumed the least. When these carbohydrates were separated into high- and low-glycemic index categories, increased intake from high-glycemic index foods was significantly associated with greater risk of coronary heart disease, whereas low-glycemic index carbohydrates were not. “Thus, a high consumption of carbohydrates from high-glycemic index foods, rather than the overall quantity of carbohydrates consumed, appears to influence the risk of developing coronary heart disease,” the authors write.

The one-fourth of women whose diet had the highest glycemic load had 2.24 times the risk of heart disease compared with the one-fourth of women with the lowest glycemic load.

Overall carbohydrate intake, glycemic index and glycemic load were not associated with heart disease risk in men. This could be because the adverse changes associated with carbohydrate intake, including triglyceride levels, are stronger risk factors for heart disease in women than in men, the authors note.

“We tentatively suggest that the adverse effects of a high glycemic diet in women are mediated by sex-related differences in lipoprotein and glucose metabolism, but further prospective studies are required to verify a lack of association of a high dietary glycemic load with cardiovascular disease in men,” they conclude.

In fact, the research shows that seniors who intentionally exercised and/or modified their diets to lose weight were half as likely to die within eight years of follow-up as their peers who did not work toward weight loss, said M. Kyla Shea, Ph.D., first author on the study and a research associate in the Department of Internal Medicine, Section on Gerontology and Geriatric Medicine.

“It was an unusually strong and surprising finding,” Shea said. “Our data suggest that people should not be concerned about trying or recommending weight loss to address obesity-related health problems in older adults.”

The study, funded by the National Institute on Aging, is currently available online and is schedule to appear in a future print issue of the Journal of Gerontology: Medical Sciences.

Prior to this study, research that has looked at the association between mortality and weight loss has not factored in the many different potential causes of the weight loss. So, using a more rigorous randomized trial approach, Shea and colleagues sought to prove or disprove the idea that older individuals who actively tried to lose weight increased their risk of death.

The research team re-analyzed data from a study of 318 community-dwelling, older adults over age 60, all with knee arthritis, who were enrolled in a trial assessing the effects of weight loss and/or exercise on physical function in the late 1990s. The initial weight-loss intervention took place over a period of 18 months from 1996 through 1998, during which time the 159 individuals in the intervention groups actively lost an average of 10.5 pounds. The non-intervention group lost an average of 3.1 pounds naturally.

The researchers then checked to see if the study participants were still living eight years later.

“Overall, we found that there were far fewer deaths – half the number – in the group of participants that lost weight compared to the group that did not,” Shea said.

The finding was unexpected to seasoned gerontologists.

“For years, the medical community has relied on multiple epidemiological studies that suggested that older people who lost weight were more likely to die,” said Stephen B. Kritchevsky, Ph.D., director of the J. Paul Sticht Center on Aging at the Medical Center. “Weight loss in old folks is just understood to be a bad prognostic sign. The data that people have been using has been unable to separate the cause and effect of the weight loss, however, and our study suggests that the weight loss they’ve been studying may be the result of other health problems and not of intentional weight loss.”

The participants in this study had a constellation of common health problems occurring in aging adults, Kritchevsky added.

“These were the seniors living out in the community, getting around and doing their daily tasks just like your neighbor,” he said. “All were overweight and dealing with the signs of aging when the study started.”

When the researchers evaluated the effect of weight loss in the oldest of the participants – 75 and older – they found the same reduction in mortality as they saw in the younger group – those 60 and older – who lost weight.

Weight loss in older adults has been shown to help several medical problems, Kritchevsky said, such as high blood pressure, high cholesterol and high fasting glucose levels. However, physicians have been hesitant to recommend weight loss in older adults because of a concern for mortality based on previous research.

“This study puts to rest a lot of unfounded concerns about how to address the epidemic of obesity among our older adults,” Kritchevsky said.

He cautioned that the study was relatively small and the results should be confirmed in other trials, but that the data gathered from this analysis are sufficient enough to rule out any significant excess risk due to intentional weight loss and to suggest that there may be a mortality benefit to losing the weight, as well.

Adding experimental telaprevir, an infection-treating protease inhibitor co-developed by Vertex Pharmaceuticals and Johnson & Johnson, to established anti-viral treatments peginterferon and ribavirin, can cure 93 percent to 100 percent of patients infected with hepatitis C genotype 1, one of the hardest types to cure, said researchers at the International Liver Congress 2010, the annual meeting of the European Association for the Study of the Liver.

Patients taking standard peginterferon and ribavirin alone have an average 51 percent cure rate, statistics indicate.

Hepatitis C is an infectious disease chronically infecting 170 million people worldwide. It is one of the top three causes of cancer death in men and a major cause of cancer death in women.

Spread by blood-to-blood contact, the disease can lead to advanced liver scarring, known as cirrhosis, as well as liver failure or liver cancer.

Even after a liver transplant, the virus almost always recurs, statistics indicate.

The study presented Friday involved 161 European and U.S. patients who enrolled in a phase II trial, designed to see how well the new drug worked in various doses after its initial safety was confirmed.

“This trial is really helpful as it shows that patients with a good early virological response only need 24 weeks of treatment and that a twice-daily dose of telaprevir is just as effective as three times a day,” hepatology Professor Mark Thursz of London’s Imperial College of Science, Technology and Medicine said.

“Although the number of patients in this study was relatively small and should therefore be treated with caution, I expect such findings will make an important contribution in terms of patients’ adherence to their therapy and overall treatment outcomes,” he said. “This will ultimately impact on their overall quality of life.”

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. 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. An estimated 1.5 million children and adults in the U.S. currently (as at 2007) have some form of autism. Presenting these statistics another way; autism spectrum disorders are believed to affect approximately 1 in 166 children.

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.

See http://www.stemcells21.com

Weight reduction aids in lowering high blood pressure, elevated cholesterol and high fasting glucose levels, all of which can increase with aging, yet some health care practitioners have hesitated recommending weight loss to older individuals due to findings that associated weight reduction with increased mortality. However, the studies upon which these conclusions were based did not address whether weight loss was intentional or due to underlying disease.

M. Kyla Shea, PhD and her associates at Wake Forest University Baptist Medical Center analyzed data from 318 arthritic men and women over the age of 60 who participated in a randomized trial that evaluated the effects of dieting and/or exercise on physical function. Known cardiovascular disease, severe hypertension, chronic obstructive pulmonary disease, and other conditions that could limit participation in regular exercise were criteria for exclusion. The 159 subjects in the weight loss diet and diet plus exercise intervention groups lost an average of 10.5 pounds over an 18.5 month period, while the exercise only group and the healthy lifestyle control participants lost an average of 3.1 pounds.

The current study analyzed deaths that occurred up to 8 years after the trial’s conclusion. Dr Shea and colleagues discovered a correlation between weight loss and increased survival. Fifteen deaths occurred among those assigned to weight loss diet interventions, compared with 30 in the remainder of the participants. “It was an unusually strong and surprising finding,” stated Dr Shea, who is a research associate in Wake Forest’s Department of Internal Medicine, Section on Gerontology and Geriatric Medicine. “Overall, we found that there were far fewer deaths – half the number – in the group of participants that lost weight compared to the group that did not.”

“These were the seniors living out in the community, getting around and doing their daily tasks just like your neighbor,” noted coauthor Stephen B. Kritchevsky, PhD, who is the director of the J. Paul Sticht Center on Aging. “All were overweight and dealing with the signs of aging when the study started.”

“For years, the medical community has relied on multiple epidemiological studies that suggested that older people who lost weight were more likely to die,” he remarked. “Weight loss in old folks is just understood to be a bad prognostic sign. The data that people have been using has been unable to separate the cause and effect of the weight loss, however, and our study suggests that the weight loss they’ve been studying may be the result of other health problems and not of intentional weight loss.”

“This study puts to rest a lot of unfounded concerns about how to address the epidemic of obesity among our older adults,” he concluded.
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Health Concern Life Extension Highlight
Obesity

The risk of death from all causes, including cardiovascular disease and cancer, increases with rising obesity in both men and women in all age groups, and the risk associated with a high BMI is greater for whites than for blacks (Calle et al 1999).

Obesity increases the risk of developing metabolic syndrome and coronary heart disease (Shirai 2004); type 2 diabetes (Mensah et al 2004); osteoarthritis of major load-bearing joints, such as the knee (Felson et al 1997); hypertension (high blood pressure); sleep apnea (periods of suspended breathing during sleep) (Wolk et al 2003); and gall bladder disease (Petroni 2000).

The International Agency for Research on Cancer has classified obesity as a critical causal risk factor for cancers of the colon, breast (postmenopausal women), endometrium, kidney (renal cell), and esophagus (adenocarcinoma) (Calle et al 2004).

A study reported in the Journal of the American Medical Association suggests that obesity causes 111,909 deaths annually (Flegal et al 2005), while epidemiological evidence shows that a lower body weight is associated with lower mortality risk (Stevens 2000). In the well-known Framingham Heart Study, risk of death increased by 1 percent for each extra pound (0.45 kg) of weight between age 30 and 42 and increased by 2 percent between age 50 and 62 (Solomon et al 1997; Kopelman 2000).

In order to prevail against your body’s innate propensity to store fat, you must restore fat-reducing hormones such as DHEA and testosterone lost to aging, and suppress hormones such as insulin and estrogen, which promote body fat. You’ll want to enhance insulin sensitivity and maintain a youthful metabolic rate so that your cells are able to release stored fat.

Such stem cell replacement therapy rely on the transplantation of healthy and vibrant cells that have been isolated and multiplied in an environment outside the body. These stem cells, utilizing adult stem cells, autologous (self) stem cells or umbilical cord stem cells are then injected into the body or skin, depending on need, to supply a healthy source of new cellular growth.

Pre-engineered adult stem cells are often utilized in such research. Adult stem cell therapy or autologous stem cells utilizes a patient’s own stem cells harvested through a typical blood draw. Patients receive injections of the new cell growth about a week later. The injected adult stem cells then stimulate the regrowth of tissues and cellular structures throughout the body or in specific areas where they are injected.

Advanced, integrative treatment is available in Bangkok, Thailand.