New Drug May Help Prevent Brittle Bones, Weight Gain During Menopause

A new drug may hold promise for older women suffering from menopause-related bone loss and weight gain, thanks to research from a UCF biomedical engineer.

In a recent study, published in the Advanced Science journal, College of Medicine scientist Melanie Coathup found that a drug, P7C3, which is also being studied to treat neurological diseases such as Alzheimer’s, showed success in preventing conditions faced by many postmenopausal females.

“P7C3 has not been investigated for bone loss or osteoporosis before, so this study is significant in discovering a new therapy that may, in the future, help mitigate this major public health issue,” Coathup says.

A reduction in estrogen levels during menopause has been thought to cause osteoporosis safely is in women, but there is no effective treatment for bone loss that can be used safely long-term. Some therapies can actually increase risks for bone loss and fracture over time. Others have been linked to increase risks for cardiovascular and cerebrovascular events and various cancers.

Coathup’s goal is to find a more effective drug that can be used long-term with little or no side effects.

P7C3 (pool 7, compound 3) is an aminopropyl carbazole, a set of compounds that have been studied for their potential therapeutic effects on the nervous system. P7C3 was discovered in 2010 and has been shown to protect neurological cells. For that reason, scientists are investigating it as a potential treatment for treating Alzheimer’s disease, ALS, Parkinson’s and other neurodegenerative disorders. It is safe and non-toxic and boosts the metabolic activity of cells.

Collaborating with postdoctoral fellow Fei Wei, Coathup found that P7C3 also protected bones in models that had low estrogen.

“Our results are exciting in that the small molecule P7C3 prevented bone loss, so that a healthy volume of bone was maintained, and the bone remained strong  — it was more difficult to break with a machine — despite our models having low to no estrogen,” Coathup says.

“P7C3 has not been investigated for bone loss or osteoporosis before, so this study is significant in discovering a new therapy that may in the future help mitigate this major public health issue,” she explains.

Osteoporosis is often related to over-activity of bone-absorbing cells in the body. Coathup’s study found that P7C3 stopped these cells from being overactive. It also reduced inflammation, and drove stem cells to form bone tissue using key proteins and signaling pathways that are important to creating healthy bone.

The researchers also found P7C3 prevented weight gain often associated with menopause. P7C3 increased the activity of a beneficial bacteria in the gut microbiome, reducing inflammation and encouraging fat metabolism.

“Massive whole-body weight gain in fat is common in both humans and rats in postmenopausal osteoporosis and low estrogen,” Coathup says. “However, when we administered the P7C3 prevented this increase in whole body fat deposits, similar to the group of rats that were given estrogen as a control group.”

In a previous study, Coathup and Wei also found that P7C3 also protected bones against damage from radiation therapy at doses used in cancer patients and has also shown tumor-killing properties against certain types of cancer. Bone absorbs more radiation than other tissues and so is a common site of injury during radiation treatment. Although the radiation targets the tumor, surrounding healthy bone is also significantly damaged.

“One of our previous studies showed that P7C3 was highly effective in preventing bone damage and reduced the risk of bone fracture in rats following exposure to ionizing radiation at levels similar to those given during radiotherapy,” Coathup says. “Amazingly, at the same effective protective dose, the P7C3 significantly reduced triple-negative breast cancer cells, and metastatic prostate cancer cell growth in the culture dish.”

Future studies will examine whether the drug can treat or reverse osteoporosis in patients who have already been diagnosed as well as examine any long-term side effects of treatment.