ITP treatment Doptelet may help prevent bone loss in osteoporosis
Preclinical study explored value of repurposing therapy for bone diseases
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The approved immune thrombocytopenia (ITP) treatment Doptelet (avatrombopag) may be able to be repurposed to treat certain bone diseases, according to a new study conducted in preclinical models.
Findings indicate Doptelet can disrupt the activity of cells that break down bones. Researchers think it might be useful for osteoporosis, especially when it occurs in people who also have ITP.
“Our work also exemplifies how repurposing existing drugs can potentially yield transformative solutions for complex diseases,” the investigators wrote. The study, “The immune thrombocytopenia therapeutic Avatrombopag alleviates osteoporosis by targeting NFATc1 signaling,” was published in the European Journal of Pharmacology.Â
ITP is an immune disorder marked by antibodies that attack and destroy cell fragments called platelets that help blood clot. Doptelet is an oral therapy that mimics the activity of thrombopoietin, a naturally occurring hormone that triggers the body to increase platelet production. It’s sold by Sobi, which was not involved with this study.
In osteoporosis, bones become abnormally weak and brittle, increasing the risk for breaks and fractures. It’s particularly common among postmenopausal women and the elderly. While some osteoporosis treatments are available, there are still many unmet needs in osteoporosis care, particularly for safer ones that provide long-lasting benefits.
Testing Doptelet’s effect on osteoporosis
Scientists in China screened drugs approved in the U.S. to look for medications that may be repurposed to treat osteoporosis. Repurposing medicines has several advantages over designing a new therapy from scratch — it’s cheaper and approved therapies already have established safety profiles, so clinical testing can usually be done faster.
“Drug repurposing … offers a cost-effective and efficient strategy for therapeutic development,” wrote the researchers, who were looking for medicines that can reduce the activity of osteoclasts, one of the two key types of bone cell. Osteoclasts are responsible for breaking down unneeded bone tissue. The other main type — osteoblasts — make new bone tissue.
Under normal circumstances, osteoblasts and osteoclasts work in a delicate balance to ensure that bones stay healthy, without getting too brittle or too dense. But in osteoporosis, this balance is disrupted — osteoclasts break down too much bone, and osteoblasts don’t make enough to compensate. The researchers reasoned that medicines that can reduce osteoclast activity could limit bone being broken down, thus helping to strengthen bones in osteoporosis.
Through their screen and other cell experiments, the scientists showed that Doptelet can block the development of osteoclasts by inhibiting NFATc1, a protein that helps regulate the genetic activity of osteoclasts and is key for their development. There are no approved osteoporosis treatments that target this protein, the researchers noted.
Further tests using a mouse model of osteoporosis induced by removing the ovaries (which mimics hormonal changes that occur in menopause) showed that Doptelet protected against bone loss.
The data indicate Doptelet is “a promising repurposed therapy for osteoporosis, offering both efficacy and an established safety profile,” wrote the scientists, who noted that this treatment may be particularly beneficial when osteoporosis affects people who also have ITP or other blood disorders. “Its dual action — targeting NFATc1 and boosting platelet production — could address a critical need in patients with combined hematologic [blood] and skeletal conditions,” they wrote.
The scientists called for clinical trials to explore the safety and effectiveness of Doptelet in people with osteoporosis.
