Their work was featured recently in a Science magazine article noting the latest advances in preventing or reversing bone loss from osteoporosis. It highlighted their synthetic hormone, which has strengthened bones in mice without the possible side effects of the traditional treatment of hormone replacement.

“Our goal is to rebuild bone, not just stop further loss,” said Manolagas, who also is director of the Division of Endocrinology and Metabolism and the Center for Osteoporosis and Metabolic Bone Disease in the Department of Internal Medicine at UAMS.

Compounds, like estren, are getting ready to be used in human trials, Manolagas said, but another exciting element of the work is the potential for using the same technology to treat other diseases.

“If we can prove the concept we developed here at UAMS for osteoporosis, it could be true for other nuclear receptors,” he said, referring to the part of the cell that binds with estren. “That would open up a whole new class of pharmacology for diseases beyond osteoporosis.”

In its September article “Coming to Grips With Bone Loss,” the national journal noted new therapies and treatments for bone deterioration, including estren. Manolagas agreed with the consensus that the prognosis for treating and preventing bone loss has improved dramatically in the past 10 to 15 years.

Identified by Manolagas’ team in 2002, estren strengthens bones by altering the work of two types of cells that constantly remodel the skeleton: the bone-building osteoblasts and the bone-dissolving osteoclasts. Estren not only copies the effects of the natural hormone estrogen by prolonging the life of osteoblasts while stimulating the destruction of osteoclasts but also helps to generate new osteoblasts without the possible side effects of estrogen.

Hormone replacement therapy has fallen out of favor, noted Science, since 2003 when the Women’s Health Initiative reported that extended therapy increased the risk of both breast cancer and cardiovascular disease. Hormones like estrogen operate in two ways in the body, launching separate cascades of signals, Manolagas and his colleagues have found in previous studies. The so-called “genotropic” signaling pathway regulates the expression of genes in the cell nucleus. This pathway has been linked to cancer development in reproductive tissues.

The “non-genotropic” pathway promotes bone growth without the cancer risk. Manolagas and his team place estren in a group of compounds they call “ANGELS,” for Activators of Non-Genomic Estrogen-Like Signaling.

These non-gentropic pathways also could be available for other cell receptors, offering possibilities for drugs that could address other diseases.

Development of estren as a pharmaceutical continues by Nuvios, a company co-founded by Manolagas as Anabonix Inc. when it started through the UAMS biotechnology business incubator BioVentures. Nuvios’ name means essentially “new life” as “vios” is Greek for new, which is appropriate given Manolagas’ Greek heritage.

“This is another success story for UAMS and the incubator,” he said, “and it is an extension of UAMS’ mission to search through research to discover new ways to heal and serve.”

Manolagas said he believed trials for estren with human patients could begin within the next year or so.