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Long-term monkey tests back Oxford’s gene therapy

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Long-term monkey tests back Oxford’s gene therapy

Long-term tests on monkeys using Oxford BioMedica’s gene therapy ProSavin suggest it can treat Parkinson’s disease without causing the jerky, involuntary movements associated with current drugs, researchers said on Wednesday.

Parkinson’s is caused by lack of the brain chemical dopamine. Standard treatment involves oral drugs that briefly raise dopamine levels — but levels of the chemical still remain unstable, leading to a movement disorder called dyskinesias.

By contrast, tests on macaque monkeys found the gene therapy safely restored concentrations of dopamine in the brain, corrected motor deficits and prevented dyskinesias — with no severe adverse side effects.

French researchers observed the animals for up to three and a half years in the study, after first inducing Parkinsonian syndrome by giving a neurotoxin and then treating them with gene therapy injections.

“Gene therapy-mediated dopamine replacement may be able to correct Parkinsonism in patients without the complications of dyskinesias,” Bechir Jarraya and colleagues wrote in the journal Science Translational Medicine.

Oxford BioMedica is currently conducting Phase I/II clinical trials with ProSavin and in July announced encouraging initial results.

ProSavin, which is administered directly to the striatum in the brain, delivers three genes required to convert cells that normally do not produce dopamine into cells that do.

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Breast defence

storage.canoe.ca

Breast defence

Some women have specific genetic problems but those breast cancers number less than 10% of all. One expert recently told me that breast cancer causes are “multifactorial” and that the combination of lifestyle factors and genetic vulnerabilities that accounts for the abnormal growth of cells is still being figured out.

That means that most of the 22,700 Canadian women (and 180 men) expected to be diagnosed this year won’t even know what caused their illness. Neither will the 5,400 women who die from it. Sometimes we forget just how many different factors may contribute to breast cancer’s development. Here’s what’s known:

ESTROGEN

The more estrogen a woman makes over time or takes through post-menopausal combined hormone replacement therapy, the higher her risk for getting breast cancer. The more years a woman menstruates, the longer breast tissue is estrogen-exposed. Birth control pills only slightly increase risk.

AGE

The chance of getting breast cancer increases as a woman ages. According to Dr. Love, from 20 to 30 the risk is one in 2,000; from 40 to 49 the risk is one in 68; from 60 to 69 the risk is one in 26. After the age of 70, a woman has a one-in-eight chance of getting breast cancer.

ALCOHOL

The risk of breast cancer jumped by 30% in women who drank more than three drinks daily.

FAMILY HISTORY

Having a mother, sister or daughter with breast cancer almost doubles a woman’s risk, particularly if the relative was diagnosed before age 50. A family history of ovarian cancer also increases the risk of developing breast cancer.

RADIATION

Radiation therapy for a previous cancer heightens the risk of breast cancer. The risk is highest if there was chest radiation during puberty.

OBESITY

Post-menopausal women who are obese are more at risk; fat cells play a role in estrogen production so being overweight adds to risky estrogen exposure.

GENETIC MUTATIONS

Those who have inherited changes in the BRCA1 and BRCA2 genes have a higher risk (some up to 90%) of getting the disease, and possibly at a younger age. Many other genes are also associated with breast cancer, including the HER-2/neu oncogene.

ENVIRONMENT

We’re exposed to vast amounts of hormone-mimicking and cell-interrupting chemicals in products we use and through environmental pollutants, some of which increases the risk of breast cancer.

BREAST DENSITY

Dense breast tissue, as shown on a mammogram, increases your risk. One study published in the Journal of the National Cancer Institute found that the relative risk of developing breast cancer in post-menopausal women with dense breasts was 400% higher than in women with fatty non-dense breasts.

BREAST DISEASE

Some diseases, including hyperplasia, can increase breast cancer risk by up to four-fold.

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Ageing heart can be prevented, say scientists

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Ageing heart can be prevented, say scientists

Scientists in Japan said they have uncovered evidence that shows it may be possible to delay or prevent heart failure in humans.

In a paper published in the journal Circulation, Tetsuo Shioi, lead researcher and assistant professor of medicine at Kyoto University Graduate School of Medicine in Kyoto, and his team described how they managed to suppress a variety of the P13K gene in a group of elderly mice.

The gene regulates the lifespan of cells and plays a role in the aging of tissues. In previous studies, suppression of this gene extended the lifespan of the roundworm and kept the hearts of old fruit flies healthy.

Compared with another group of mice in which the gene was left intact, mice with the suppressed gene had improved cardiac function, less fibrosis (which makes the heart inflexible) and fewer biological markers of aging.

“This study showed that aging of the heart can be prevented by modifying the function of insulin and paves the way to preventing age-associated susceptibility to heart failure,” Shioi said.

Old age is a major risk factor for heart failure, a condition when the heart is unable to pump enough blood around to supply the oxygen the body needs, the World Health Organization says.

According to the American Heart Association, 5.7 million Americans have heart failure, and nearly 10 out of every 1,000 people over age 65 suffer heart failure every year.

Mariell Jessup, professor of medicine at the University of Pennsylvania School of Medicine in Philadelphia, said older people experience a slow but gradual loss of heart cells and a host of other cellular abnormalities which make the remaining cells contract less efficiently.

“This early work in a mouse model, clarifying the role of PI3K in cardiac aging, could ultimately allow scientists to understand if human hearts are similarly influenced,” he said.

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