Osteoporosis is a common disease that weakens bone structure with age. Current treatments for osteoporosis work very well in halting bone loss, but they lack the ability to promote bone growth and cannot be taken orally. promising in terms of According to this preliminary evidence, this finding may pave the way for specific and effective new treatments with minimal side effects.
Scientists have recently established that a hormone receptor called relaxin family peptide receptor 2 (RXFP2) is important for the formation and maintenance of healthy bones. A collaborative group of scientists led by geneticist Alexander Agoulnik of Florida International University and pharmacist Juan Marugan of the National Institutes of Health (NIH) found that increased RXFP2 activity could increase bone formation in conditions like osteoporosis. I hypothesized that there is.
“What you want to do is more than prevent bone removal. You want to promote new bone differentiation, which is really compromised.”
The team screened over 80,000 potential compounds to find compounds that bind to RXFP2 and enhance its function, also known as agonists. To see if the top four agonists they identified affected bone density, she treated human osteogenic cells with three different doses of each compound. One compound, called 6641, stood out from the rest by dramatically enhancing bone mineralization, a sign of bone strength. It resulted in 3.5 times more mineralization compared to controls.
Osteoporosis is a common bone disease that alters bone structure and strength.
Credit: iStock/Bigmouse108
Further experiments in certain types of female mice with low bone density revealed that compound 6641 increased bone formation with no apparent side effects. They also showed that 6641 was effective when taken orally.
“Discovery and optimization of small-molecule RXFP2 agonists is an important first step towards the development of future therapies,” said Michelle Halls, a pharmacist at Monash University who was not involved in the study. .
The team plans to follow this study by testing a mouse model of osteoporosis to confirm the dose and duration of treatment needed. We plan to investigate side effects.
“While this initial data looks promising, we still have a long way to go in terms of other models, dose-response and toxicity evaluations. We need to get them to move into clinical development,” said Mulgan. “It’s really hard.”
Still, the team continues to investigate the efficacy and safety of potential treatments and plans to help patients in the future.
The molecule could also be useful in treating other bone diseases, said Mulgan. “We want to go beyond just osteoporosis. We have good treatments now, but they have limitations. But for rare diseases, we have almost nothing.”
reference
Esteban-Lopez, M., Wilson, KJ, Myhr, C. and others. Discovery of small molecule agonists of relaxin family peptide receptor 2. symbiote Five1183 (2022).