Current and Future Use of Chloroquine and Hydroxychloroquine in Infectious, Immune, Neoplastic, and Neurological Diseases: A Mini-Review

Abstract

The process of finding new therapeutic indications for currently used drugs, defined as 'repurposing', is receiving growing attention. Chloroquine and hydroxychloroquine, with an original indication to prevent or cure malaria, have been successfully used to treat several infectious (HIV, Q fever, Whipple's disease, fungal infections), rheumatological (systemic lupus erythematosus, antiphospholipid antibody syndrome, rheumatoid arthritis, Sjögren's syndrome), and other immunological diseases. Indeed, they have anti-inflammatory, immunomodulating, anti-infective, antithrombotic, and metabolic effects. Among the biological effects of chloroquine and hydroxychloroquine, it is important to highlight their antitumoral properties, likely due to their strong antiproliferative, antimutagenic, and inhibiting autophagy capacities. These effects make these drugs a possible option in the treatment of several tumors in association with radiotherapy and chemotherapy. Finally, the repurposing of chloroquine and hydroxychloroquine is currently being examined for neurological diseases such as neurosarcoidosis, chronic lymphocytic inflammation with pontine perivascular enhancement responsive to corticosteroids, and primary progressive multiple sclerosis. Several ongoing clinical trials have been testing these drugs in non-neoplastic and neoplastic diseases. Moreover, the well-demonstrated good tolerability of chloroquine and hydroxychloroquine make them safe even during pregnancy. Gastrointestinal and cutaneous manifestations are considered not to be serious, while retinal, neuromuscular, and cardiac toxicities are classified as serious adverse events.