Monoclonal antibodies for the management of central nervous system diseases: clinical success and future strategies

ABSTRACT

Introduction

Recombinant monoclonal antibodies (mAbs) are highly selective and effective biologicals with proven utility as therapeutics. mAbs have demonstrated substantial promise in the treatment of several central nervous system diseases.

Areas covered

Databases including PubMed and Clinicaltrials.gov were used to identify clinical studies of mAbs involving patients with neurological disorders. This manuscript reviews the current status and recent advances in the development and engineering of therapeutic blood-brain barrier (BBB)-crossing mAbs and their potential in treatment of central nervous system diseases, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), brain tumors, and neuromyelitis optica spectrum disorder (NMSOD). In addition, the clinical implications of recently developed monoclonal antibodies are also discussed, along with the strategies to enhance their BBB permeability. The adverse events associated with the administration of monoclonal antibodies are also presented in the manuscript.

Expert opinion

There is growing evidence that supports the therapeutic utility of monoclonal antibodies in central nervous system and neurodegenerative diseases. Several studies have offered evidence of clinical efficacy in AD through use of anti-amyloid beta antibodies and anti-tau passive immunotherapy-based strategies. Additionally, ongoing research trials have produced promising findings for the treatment of brain tumors and NMSOD.

KEYWORDS:

• Alzheimer’s disease
• bispecific antibodies
• blood-brain barrier
• brain drug delivery
• central nervous system disorders
• molecular trojan horse
• multiple sclerosis
• recombinant monoclonal antibodies

Article highlights

• Monoclonal antibodies with ability to cross BBB are an emerging class of therapeutics to treat central nervous system disorders and are a promising target for AD, PD, NMSOD and brain tumors.

• Anti-amyloid beta antibodies and anti-tau passive immunotherapy have a pivotal role in the treatment of Alzheimer’s disease in different stages.

• The first anti-VEGF monoclonal antibody, bevacizumab, has increasingly been used in the treatment of recurrent glioblastoma.

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

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

This paper was not funded.