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Azithromycin as a neuroprotective drug

AzithromycinDrug repurposingImmunomodulationIschemic strokeNeuroprotection

Introduction

The invention refers to a new use of azithromycin as a neuroprotective drug for the treatment or prevention of brain damage caused by ischemic stroke. The invention suggests that azithromycin is a promising candidate to be developed as effective and safe pharmacological approach for the treatment of ischemic brain damage.

Technical features

Ischemic stroke is a major cause of death and long-term disability worldwide. The only approved therapy relies on mechanical or pharmacological reperfusion of the injured tissue and, due to the narrow therapeutic window, can be used in <10% patients. In stroke animal models, azithromycin exerts neuroprotection through immunomodulation, as it promotes polarization of microglia/macrophages towards the M2 protective phenotype, while reducing brain infiltration of inflammatory neutrophils. As a consequence, it reduces brain infarct volume and blood-brain barrier damage and ameliorates neurological deficits up to 7 days after the insult. This innovative mechanism, together with the relatively low toxicity profile, already established in humans, will allow to overcome the major sources of attrition that have hampered the development of stroke therapeutics during the last decades, namely lack of efficacy and/or excessive toxicity.

Possible Applications

  • Treatment or prevention of acute ischemic stroke;
  • Treatment of acute or chronic neurodegenerative diseases with a strong inflammatory component.

Advantages

  • The drug is already available on the market;
  • Toxicity is already established in human;
  • The human target has partially been validated;
  • The risk of clinical trial failure is dramatically reduced;
  • The drug can be rapidly translated to the clinic.