Rapamycin, traditionally used as an immunosuppressant, is emerging as a potential therapeutic agent for oral health issues, including periodontitis and oral cancer. Dr. Jonathan An from the University of Washington School of Dentistry has received FDA approval to study rapamycin in patients with periodontitis, building on evidence suggesting its positive effects on oral health in transplant patients.
Rapamycin and Periodontitis
Periodontitis, a chronic inflammatory disease affecting the tissues surrounding teeth, is often associated with oxidative stress and bone loss. A previous study using elderly mice with periodontitis demonstrated that short-term rapamycin treatment improved periodontal health. The study indicated that rapamycin could regenerate periodontal bone, reduce gingival and periodontal bone destruction, and shift the oral microbiome to a more youthful composition. Rapamycin's ability to suppress oxidative stress may prevent bone loss, offering a therapeutic avenue for tissue regeneration in periodontal disease.
Rapamycin primarily inhibits the mechanistic target of rapamycin (mTOR), influencing cellular processes, including oxidative stress. In many instances, rapamycin reduces oxidative stress by promoting autophagy, enhancing mitochondrial function, and reducing inflammation, leading to decreased production of reactive oxygen species (ROS). However, the effects of rapamycin on oxidative stress are context-dependent, with high doses potentially interrupting the wound healing process.
Potential in Oral Cancer Treatment
Oral squamous cell carcinoma (OSCC), the most prevalent type of oral cancer, often carries a poor prognosis due to late diagnosis and aggressive progression. The mTOR pathway is frequently activated in OSCC, contributing to tumor growth and survival. Preclinical studies suggest that rapamycin, by inhibiting mTOR, can reduce the growth of oral cancer cells and enhance the effects of other anticancer therapies. A study showed that rapamycin inhibits oral cancer cell growth by promoting oxidative stress and suppressing ERK1/2, NF-κB and beta-catenin pathways. While further research is needed to confirm these effects in humans, initial results are promising, suggesting rapamycin could be integrated into oral cancer treatment protocols.
Implications for Dental Procedures
The mTOR pathway is crucial for cell growth and repair, and by targeting this pathway, rapamycin may promote oral tissue regeneration following surgery or injury. This has significant implications for patients undergoing dental procedures, such as tooth extractions or implants, where rapid and effective healing is essential. Dosage considerations are vital, as high doses of rapamycin have been shown to impede the wound healing process.
