Future perspectives for cryptococcosis treatment

Abstract

Cryptococcosis is one of the most devastating human fungal infections. Despite its impact, none of the standard antifungals were developed after 1990. New, improved, less toxic, affordable and widely available treatment is, therefore, imperative. Areas covered: This review offers an insight into technological developments for cryptococcosis disclosed in patent literature. From a broad search of patent documents claiming cryptococcosis treatment and having earliest priority between 1995 and 2015, we selected and summarized compounds/molecules (i) revealed in documents disclosing in vivo activity against Cryptococcus spp. or (ii) found in the pipeline of companies that appeared as assignees in our patent search. This information was complemented with data on compounds under development for this indication from the database Integrity (Clarivate Analytics). Expert opinion: This review demonstrates that drug development against cryptococcosis is discrete. However, it also shows that the existing development is not focused on a single class of molecules, but on different types of molecules with distinct fungal targets, reflecting the complexity of generating novel anti-cryptococcal tools. Given the intrinsic difficulties and high costs of drug development and the evident market failure in this field, we consider drug repurposing the most promising avenue for cryptococcosis treatment.

Drug development for cryptococcosis treatment: what can patents tell us?

“…The academic sector seems to have a slightly more prominent role, given that the top assignees and most-cited inventors are from this classification, as are 64% of the patents that actually disclose in vivo evidence against Cryptococcus sp. 25 This finding is in agreement with the idea that currently both the academic sector and pharmaceutical companies play important roles in drug development for NTDs. According to a recent study, the public sector and philanthropic organisations sponsored the largest share of clinical trials for neglected diseases registered at clinicaltrials.gov between 2005 and 2015.…”

“…is quite low, despite the increasing trend since 2012; and (ii) none of the top inventors from our patent search list cryptococcosis as their main line of research, although some focus on the development of antibacterial and antifungal compounds and on other NTDs (data not shown). These findings are also supported by previously published analyses of this same patent collection, 25 which indicate the following: (i) cryptococcosis had a secondary position in most of these patents; (ii) experimental evidence against Cryptococcus sp. was usually very preliminary, consisting mostly of MIC (minimal inhibitory concentration) tests; and (iii) less than 5% of the companies appearing as assignees in our selected patent documents actually included cryptococcosis treatment in their publicly available pipeline.…”

Disseminated and Relapsing Cryptococcosis: What We Still Have to Learn—a Case Series and Review of Literature

“…Never a doubt that amphotericin B is the milestone of anticryptococcal therapy, but half a century after the introduction of it, the management of cryptococcosis remains indeed unsatisfactory. Research about innovative drugs is warranted, with several antimicrobial agents showing in vitro activity against Cryptococcus [38] but such discussion is beyond the scope of this review.…”

New Approaches for Cryptococcosis Treatment

“…AR-12, a small molecule derived from celecoxib, was tested as an antitumoral agent in phase I clinical trials, and licensed to Arno Therapeutics (NCT00978523) [75]. AR-12 is a non-nucleoside acetyl CoA synthetase inhibitor as previously investigated in S. cerevisiae and C. albicans [76].…”