World's First Clinical Trial Of Pioneering Stem Cell Bandage To Treat Torn Meniscal Cartilage

Millions of people with knee injuries could benefit from a new type of stem cell bandage treatment if clinical trials are successful. The world's first clinical trial for the treatment of patients with torn meniscal cartilage has received approval from the UK regulatory agency, the MHRA1, to commence.

The current treatment for the majority of tears is the removal of the meniscus, a procedure that often results in the early onset of osteoarthritis. The Phase I trial, one of the first in the UK to be approved using stem cells, will treat meniscal tear patients with a cell bandage product, seeded with the patient's own, expanded, stem cells.

The cell bandage, produced by Azellon Ltd, a University of Bristol spin-out company, is focused on the research, development and commercialisation of an adult autologous (patient's own) stem cell technology which in vitro (tissue culture) has shown great promise for the healing of meniscal tears.

The trial is designed primarily to test the safety profile of Azellon's cell bandage in ten meniscal tear patients, but some information on whether or not it works will also be obtained. The bandage, containing the patient's own stem cells will be implanted in a simple surgical procedure using a specially designed instrument that helps to deliver the cells into the injured site as a first-line treatment in place of removal of the meniscus. Patients will be closely monitored for safety over a five-year follow-up period.

Professor Anthony Hollander, Chief Scientific Officer at Azellon Ltd and Head of the School of Cellular and Molecular Medicine at the University of Bristol, said: "The approval we have received from the MHRA is an important milestone in the development of stem cell therapies in the UK. These cells hold much scientific and medical promise but we can only know if they work or not by testing them out in clinical trials."

Professor Ashley Blom, Professor of Orthopaedic Surgery at the University of Bristol, added: "The effective repair of meniscal tears would represent a significant advance in treatment, particularly for younger patients and athletes by reducing the likelihood of early onset osteoarthritis, and would offer an exciting new treatment option for surgeons."

More than 900,000 patients have meniscal tears every year in Europe with perhaps 800,000 to one million meniscal repairs in US making the total market 1.7 million meniscal tears per year. Seven per cent of meniscal surgeries are repairs in the 'red' zone, the rest (1,581,000 tears) remain total or partial menisectomies. Meniscus tears normally occur in active and younger people (estimated 80 per cent of meniscal patients are younger than 50). Meniscus tear is a common sports injury and is especially prevalent amongst competitive athletes in football (including US and Australian rules), rugby and basketball. Patients who have partial or total menisectomy have an increased risk of developing osteoarthritis over the following 4.5 to eight years.

Azellon Ltd is funded by the Wellcome Trust, Technology Strategy Board and early stage investors IPGroup, Oxford Technology and Wyvern Seedcorn fund.

Source:
Caroline Clancy
University of Bristol

Parental Gender Affects Fetal Programming Of Disease Risk To Next Generation

Overexposure to stress hormones in the womb can program the potential for adverse health effects in those children and the next generation, but effects vary depending on whether the mother or father transmits them, a new animal study suggests. The results were presented Saturday at The Endocrine Society's 93rd Annual Meeting in Boston.

"This research sheds light on how babies who are exposed in the womb to excessive levels of stress hormones, known as glucocorticoids, can pass on the health effects to their own children, and how the effects vary between mothers and fathers," said the study's principal investigator, Amanda Drake, MD, PhD, a senior clinical fellow at the University of Edinburgh in Scotland.

Glucocorticoid levels may become raised during pregnancy if, for example, the mother experiences stress or illness or receives glucocorticoid drugs for treatment of illness or premature labor. Excess glucocorticoid exposure of the fetus can reduce birth weight and raise blood pressure later in life in animals and humans, and babies born with low birth weight are at increased risk of diabetes and heart disease in adulthood, Drake said.

"This has led to the concept of fetal programming, suggesting that the environment experienced in the womb can affect development, resulting in an increased risk of later disease. This increased disease risk can be passed to the next generation," Drake said.

Using a rodent model of early life programming, Drake and colleagues studied the effects of glucocorticoid overexposure, with the drug dexamethasone, during the last week of gestation. They studied the effects on the directly exposed offspring and on their offspring. Their prior research showed that the low birth weight induced by prenatal exposure to dexamethasone transmits to a second generation through both male and female rats, according to Drake.

This new research showed that although birth weight is reduced in the offspring of male or female rats that were exposed to dexamethasone during fetal development, this effect was more pronounced in the offspring of male rats exposed to excess glucocorticoids during development in the womb.

Additionally, although birth weight was reduced in the second generation of rats, the genes that were affected differed from those seen in their parents, Drake said. In the first generation, glucocorticoid overexposure in the womb affected genes in the liver of the fetus and in the placenta. This increased the likelihood of the baby rats having a low birth weight and increased their risk of developing diabetes and heart disease in later life, she said.

However, the genes affected in the second generation depended on whether the mother or the father had been exposed to glucocorticoids while developing in the womb, the authors reported. These affected genes that could produce adverse health effects included genes important in growth and the transport of nutrients across the placenta.

Regarding the study, which was funded by the U.K. Medical Research Council, Drake said, "It could help inform future research to find interventions that could prevent diseases such as diabetes and high blood pressure," Drake said.

Source:
Aaron Lohr
The Endocrine Society

Increased Rate Of Mortality In Obese Breast Cancer Survivors

Women with a healthy body weight before and after diagnosis of breast cancer are more likely to survive the disease long term, a new study finds. The results were presented Saturday at The Endocrine Society's 93rd Annual Meeting in Boston.

The study, conducted in nearly 4,000 breast cancer survivors, found that obesity is strongly linked to death due to breast cancer. In particular, overweight or obese women with a history of estrogen receptor-positive breast cancer, but not those with estrogen receptor-negative cancer, had a higher risk of dying of their disease, said the study's lead author, Christina Dieli-Conwright, PhD.

"This relationship between dying and being obese or overweight may depend on whether the type of breast cancer is hormonally dependent," said Dieli-Conwright, assistant research professor at City of Hope National Medical Center in Duarte, Calif.

The research involved participants of the large California Teachers Study who, between 1995 and 2006, received a diagnosis of invasive breast cancer - cancer that has spread beyond the breast ducts. Of the 3,995 women studied, 262 died of breast cancer through 2007, the authors reported in their abstract.

They defined obesity as a body mass index (BMI, in kg/m2) of 30 or higher. The authors obtained BMI, a measure of height and weight, from questionnaires showing each participant's self-reported height and weight at baseline and at age 18. Baseline was the beginning of the study and was near, but necessarily at, diagnosis, according to Dieli-Conwright.

Women who were obese at baseline had a 69 percent higher risk of dying of their breast cancer than did nonobese women, Dieli-Conwright said. This same increased mortality, or death, risk was present in women who were overweight (BMI of 25 to 29) at age 18.

The researchers also analyzed the mortality risk by estrogen receptor status (whether the hormone estrogen fuels the breast cancer). They found that the higher the BMI, the greater the risk of dying of breast cancer for women with estrogen-dependent cancer. They saw no such link in women with estrogen-negative breast cancer. Women who are obese or overweight tend to have higher levels of circulating estrogen, which likely explains this difference, Dieli-Conwright said.

Their findings add to the growing scientific evidence that obesity raises the risk of both developing breast cancer and dying of it.

"What we know now is that there is a strong link between dying from breast cancer and being obese," Dieli-Conwright said. "And it's not just your BMI near the time you're diagnosed that's important."

She continued, "With the obesity epidemic on the rise, weight management programs using exercise and diet are vital in cancer prevention and survivorship." The National Cancer Institute and the California Breast Cancer Research Fund supported this study.

Source:
Aaron Lohr
The Endocrine Society