Cidofovir

Recurrent respiratory papillomatosis (RRP) is a chronic disease characterized by papillomatous growths in the airway, predominantly affecting the larynx and trachea. The disease is generally caused by the low-risk types of human papillomavirus (HPV), HPV6 and HPV11. The incidence and prevalence of RRP vary from country to country, and in Japan the incidence is estimated to be 0.20 per 100,000 adults, according to a recent nationwide survey. The most commonly affected region in the larynx is the true vocal folds. Surgery is the standard treatment, although preferred surgical instruments, such as the carbon dioxide laser, microdebrider, and cold instruments, have shifted over time. Currently the microdebrider is the most commonly used instrument in the United States and Europe, while cold instruments are the most common in Japan. The above-mentioned Japanese nationwide survey analyzed the outcomes of 150 newly diagnosed adult RRP patients who underwent surgery as an initial treatment, and showed that the estimated 1-year and 2-year recurrence-free rates according to the Kaplan-Meier curve were 55.8 % and 47.9 %, respectively. Recurrence was also significantly more common in patients with lesions in multiple regions than those with lesion(s) in a single region. Due to the intractable nature of the disease, adjuvant therapy is often required to control it. Although there are no standard drugs that are used with RRP, several agents have been used in clinical practice, including the intralesional injection of cidofovir, the intralesional or systemic injection of bevacizumab, and the HPV vaccine. Immunological approaches that enhance antitumor T-cell responses, such as immune checkpoint inhibitors, have also gained attention. To date, only a few small randomized controlled trials of surgery and pharmacotherapy for RRP have been published. Further research with larger cohorts and longer follow-up periods is needed to determine the appropriate treatment strategy for RRP.

Despite the fact that human adenovirus (HAdV) causes severe infections in immunosuppressed and immunocompetent individuals, especially in children, there is currently no specific treatment for these infections. Previously we reported a new salicylamide analogue, JMX0312, as a potent inhibitor of HAdV infection with low cytotoxicity in vitro. Here we evaluate the in vivo efficacy and safety of this molecule in the immunosuppressed Syrian hamster model of HAdV infection. JMX0312 administration at a dose of 6.25 mg/kg did not affect the body weight of the animals, and reduced the viral load in liver and blood in a similar way than cidofovir. Also, JMX0312 reduced the mortality of the animals, although in a lesser extent than cidofovir, a drug used to treat these infections that must be subject to rigorous monitoring due to its high toxicity and whose used is not approved in children. Our findings highlight the potential of this new antiviral agent for the treatment of HAdV infections, paving the way for future pre-clinical and clinical trial development towards a safer and more effective treatment against HAdV-associated infections.