Delivery of neurotrophic factors in the treatment of age-related chronic neurodegenerative diseases

ABSTRACT

Introduction

Neurodegenerative diseases are those wherein the neurons in the brain or peripheral nervous system lose their function, eventually culminating in neuronal death. Aging acts as the predominant factor here due to the reduced protein turnover rate in aging cells. As neurotrophic factors possess imperative roles in protecting the neurons and restoring their functionality, design of different modalities to deliver them to the brain would significantly enhance the therapeutic benefits.

Areas covered

This review covers the various mechanisms of neurodegeneration, its molecular link with aging, different neurotrophic factor classes and their potentials, current treatment strategies, the challenges associated with the delivery of neurotrophic factors, administration routes, design of different delivery vehicle design, alternative modalities of delivery, and the clinical translational challenges of these strategies.

Expert opinion

A deeper molecular level understanding about the complexity of neurodegeneration, discovery of potential biomarkers, which helps identifying the right targets, finding the accurate animal model completely recapitulating the human scenario, and a validated design of clinical trials would immensely help in overcoming the present challenges. The substantial developments in the field of gene therapy, usage of small molecules and peptide mimetics, combinatory approaches, etc. definitely give brighter hopes.

KEYWORDS:

• Aging
• BBB
• CNS delivery
• gene therapy
• neurodegeneration
• neuroprotection
• neurotrophic factor

Article highlights

• Impairment or loss of function of neurons in brain or peripheral nervous system leads to different neurodegenerative disorders which show distinct clinical manifestations.

• Aging has been considered to be the primary risk factor fundamental to majority of neurodegenerative diseases and dementia, due to age-dependent decrease in turnover rate of proteins.

• Neurotrophic factors are those growth factors which play an instrumental role in the development and protection of neuronal cells as well as restoration of their functions, which are imperative for the prevention/therapy of chronic age-related neurotrophic diseases (CAR-ND).

• The obstruction posed by blood brain barrier, compartment heterogeneity and complexity of brain and CNS hampers the development and effectiveness of the current treatment modalities.

• Design of different therapeutic strategies and modes of administration facilitating the controlled delivery of neurotrophic factors to brain and central nervous system can significantly improve the current scenario of CAR-ND treatment.

This box summarizes key points contained in the article.

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.

Additional information

Funding

This paper was not funded.