Palmitoylethanolamide as a prophylaxis or adjuvant treatment in bacterial meningitis

• Applicant: Sandra Ribes Miravet, Ph.D.
• Subject Area: Molecular and Cellular Neurology and Neuropathology ; Clinical Neurology; Neurosurgery and Neuroradiology
• Term: from 2015 to 2017
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 270676532

Every person is vulnerable to infections, regardless of gender, age, ethnics or economical status. Especially immunocompromised individuals are at a high risk of acquiring microbial infections because their immune system is impaired. In the last 70 years, antimicrobial drugs have been successfully used in the management of infections, saving millions of lives. However, the emergence of multidrug-resistant pathogens limits the efficacy of antibiotic regimens and thus new strategies are called for. In this scenario, the use of an immunostimulator that enhances the immune response, thereby protecting the host against diverse pathogens, is emerging as a promising alternative. In the planned project, we focus on bacterial meningitis, an infection in which the inflammatory response induced as a consequence of bacterial invasion leads to high rates of associated morbidity and mortality. As pathogens, we select Streptococcus pneumoniae as the most common aetiological agent of acute bacterial meningitis in immunocompetent adults and children. As representative pathogens in the immunocompromised host, we select Listeria monocytogenes and Escherichia coli. Our potential immunoactivator is palmitoylethanolamide (PEA), an endogenous compound found in most mammalian tissues, which has well-known anti-inflammatory, neuroprotective and analgesic properties. Clinically, more than 6000 patients have been successfully treated with PEA, with no adverse effects reported in any of the trials. The first aim of this proposal is to evaluate the efficacy of PEA as a prophylactic immunostimulator to increase the protection of both the immunocompetent and the immunocompromised host against bacterial meningitis. Because PEA can arrest the deleterious inflammatory cascade at an early stage of infection, the second aim is to study the efficacy of PEA as an adjuvant to antibiotic therapy in the immunocompetent/neutropenic host against meningitis. The third objective is to elucidate which receptor is involved in the potential protection against bacterial meningitis induced by PEA.

• DFG Programme: Research Grants