Minocycline for the management of multiple sclerosis: repositioning potential, opportunities, and challenges

ABSTRACT

Introduction

Multiple sclerosis (MS) is a chronic demyelinating inflammatory disorder with variable clinical and pathologic characteristics reflecting multiple underlying pathophysiologic mechanisms. Repositioning of existing drugs for the new indications offers several advantages including significant reduction in the cost and time of drug development and exemption from early phase clinical trials. Minocycline has been reported to exhibit immunomodulation in several pre-clinical and clinical studies through suppression of migratory inflammatory cells, modulation of peripheral immune response, and inhibition of microglial activation within the CNS.

Areas covered

Here, the authors review the repositioning potential of minocycline for the treatment of MS along with appraisal of the evidence obtained from preclinical and clinical research. The authors also discuss the advantages and potential safety concerns related to the use of minocycline for the management of MS.

Expert opinion

Minocycline offers several distinct advantages in terms of well-known safety profile, lower cost of therapy, widespread availability, and being available as an oral formulation. The authors call upon the public and private funders to facilitate well designed and adequately powered randomized clinical trials that can provide conclusive evidence regarding the safety and efficacy of minocycline in patients with MS.

KEYWORDS:

• Autoimmune
• adverse effects
• clinically isolated syndrome
• demyelination
• neurodegenerative
• RRMS
• repositioning
• safety

Article highlights

• Drug repositioning is a useful measure aimed to redefine the role of existing drugs for novel indications. This article reviews the repositioning potential of minocycline for the management of multiple sclerosis (MS) on the basis of the evidence obtained from preclinical as well as clinical studies.

• Due to its beneficial effects on the pathogenic mechanisms of MS viz. suppression of migratory inflammatory cells, modulation of peripheral immune response and inhibition of microglial activation within the CNS, minocycline has significant potential to be repurposed as an effective therapy for the treatment of MS.

• Minocycline also offers clinically important advantages including being orally available, having favorable pharmacokinetics, a well characterized safety profile, and being inexpensive and widely accessible.

• Pharmaceutical industry, government funding bodies, academic institutes and drug regulators should facilitate well designed and large clinical trials enabling generation of high-quality evidence to further characterize the role of minocycline in MS management.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants, or patents received or pending, or royalties.

Reviewer disclosures

A reviewer on this paper was the primary investigator on many of the previous clinical trials of minocycline in MS and CIS, and is currently funded to do a second trial in CIS/early RRMS which has not started due to COVID-19. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.