Thursday, February 08, 2001

NEW YORK (Reuters Health) - Genetically altered mice were able to bulk up their muscles and in the process have shed light on possible therapies for those with muscle-wasting disorders, such as muscular dystrophy, researchers report.

In the study, investigators altered the DNA of genetically normal, healthy mice while they were still embryos. By inserting a gene into the mouse DNA, the researchers created mice that overproduce a substance called muscle insulin-like growth factor-1 (mIgf-1), according to Sharon Hesterlee, director of research development for the Muscular Dystrophy Association (MDA) in Tucson, Arizona.

The MDA partially funded the research that was led by Dr. Nadia Rosenthal of Massachusetts General Hospital-East in Charlestown. Rosenthal's team reports the findings in the February issue of the journal Nature Genetics.

The naturally-occurring growth factor mIgf-1 is essential in mice, and helps muscle cells grow and divide. Humans also have similar growth factors that are essential to the healthy production and regeneration of muscle. As mice--and people--age, the muscles naturally lose their ability to regenerate.

After 20 months--well into middle age for a mouse--the mice producing more mIgf-1 maintained muscle mass much like that of a younger mouse, compared to litter mates that did not receive the treatment, Hesterlee explained.

These findings could eventually lead to treatments for age-related frailty, and possibly for muscle-wasting disorders such as muscular dystrophy, she said.

Most mammals--mice and men alike--lose up to one third of their muscle mass and strength as they age. It is not clear why this happens. But evidence suggests that declines in the production and activity of insulin-like growth factors (IGF)--hormones that influence the growth and repair of muscle cells--play a key role.

Since age-related changes in muscle are similar to early changes in muscle seen in patients with muscular dystrophy, it is possible that a gene therapy-type approach may provide a useful treatment for both aging-related loss of muscle function and impairments associated with muscle disease, Hesterlee said.

SOURCE: Nature Genetics 2001;27:195-200.

Copyright �2001 Reuters Limited.

Wednesday, February 07, 2001

By Julia Hancock

ROME (Reuters) - Italian scientists said on Wednesday they may have found a way to help slow down the aging process through experiments with genetically modified mice and are trying to apply their discoveries to fight muscular dystrophy.

Researchers at Rome's La Sapienza University, working with scientists at the University of Pennsylvania and the Massachusetts General Hospital in the United States, have created genetically modified super-muscle mice which are relatively immune to the muscle wasting that occurs with aging.

Tests in Rome have shown that a 22-month-old super-muscle laboratory mouse, comparable in age to an 80-year-old human, has the same type of muscle as a normal six-month-old mouse, equivalent in age to a 40-year-old human. The mice were genetically engineered to produce a growth-promoting protein called muscle insulinlike growth factor 1 (mIgf1) only in their voluntary muscles -- those which control conscious movement.

"The originality of our research was to express the growth factor in a selective way so it only affects voluntary muscles, thereby avoiding side effects in the heart, kidney or other tissues," La Sapienza's Antonio Musaro told Reuters.

FOCUS NOW ON MUSCULAR DYSTROPHY

The mIgf1 protein, normally found in muscles of healthy young people, holds the properties which prevent muscle decay caused by aging and certain muscle diseases, including some forms of muscular dystrophy.

Musaro said the project was now concentrating on seeing how their research could help fight the muscle wasting disease of muscular dystrophy.

"The goal is to use these models to develop a therapy that can be used both for old people, to reduce muscle wasting, and for sick people with illnesses like muscular dystrophy," he added.

Musaro said the project had also developed a therapeutic version of mIgf1 which can be directly injected into the aged muscles of a normal lab mouse.

The effect is the same as with the general variety of the protein, but it is limited to the specific muscle into which the virus is injected, rather than permeating all voluntary muscles.

"The experimental phase of this therapy we hope will last five years before we can start (human) trials," Musaro said.

The earliest the therapy can be commercially available is in ten years time, he added.

Copyright �2001 Reuters Limited.