From Animal Models to Clinical Trials: The Potential of Antimicrobials in Multiple Sclerosis Treatment

Abstract

Multiple sclerosis (MS) is a chronic, autoimmune, demyelinating disease of the central nervous system (CNS). Microbes, including bacteria and certain viruses, particularly Epstein-Barr virus (EBV), have been linked to the pathogenesis of MS. While there is currently no cure for MS, antibiotics and antivirals have been studied as potential treatment options due to their immunomodulatory ability that results in the regulation of the immune process. The current issue addressed in this systematic review is the effect of antimicrobials, including antibiotics, antivirals, and antiparasitic agents in animals and humans. We performed a comprehensive search of PubMed, Google Scholar, and Scopus for articles on antimicrobials in experimental autoimmune encephalomyelitis animal models of MS, as well as in people with MS (pwMS). In animal models, antibiotics tested included beta-lactams, minocycline, rapamycin, macrolides, and doxycycline. Antivirals included acyclovir, valacyclovir, and ganciclovir. Hydroxychloroquine was the only antiparasitic that was tested. In pwMS, we identified a total of 24 studies, 17 of them relevant to antibiotics, 6 to antivirals, and 1 relevant to antiparasitic hydroxychloroquine. While the effect of antimicrobials in animal models was promising, only minocycline and hydroxychloroquine improved outcome measures in pwMS. No favorable effect of the antivirals in humans has been observed yet. The number and size of clinical trials testing antimicrobials have been limited. Large, multicenter, well-designed studies are needed to further evaluate the effect of antimicrobials in MS.

Keywords: Epstein–Barr virus; animal models; antibiotics; antimicrobials; antivirals; autoimmune disease; experimental autoimmune encephalomyelitis; microbiota; multiple sclerosis; treatment.

Figure 1

Flow diagram of identification process for eligible studies per PRISMA guidelines.

Figure 2

Snapshot of antimicrobials in pwMS based on clinical studies. ARR = annualized relapse ratio, CEF = ceftriaxone, CIS = Clinically isolated syndrome, EDSS = expanded disability status scale, GE = gadolinium-enhancing, INF-beta-1a = interferon beta 1 alpha, MS = multiple sclerosis, PCN = penicillin, PPMS = primary progressive multiple sclerosis, pwMS = people with multiple sclerosis, RAP = rapamycin, TEM = temsirolimus, T25FW = timed 25-foot walk.