Have there been improvements in Alzheimer’s disease drug discovery over the past 5 years?

ABSTRACT

Introduction: Alzheimer’s disease (AD) is the most important neurodegenerative disorder with a global cost worldwide of over $700 billion. Pharmacological treatment accounts for 10–20% of direct costs; no new drugs have been approved during the past 15 years; and the available medications are not cost-effective.

Areas covered: A massive scrutiny of AD-related PubMed publications (ps)(2013–2017) identified 42,053ps of which 8,380 (19.60%) were associated with AD treatments. The most prevalent pharmacological categories included neurotransmitter enhancers (11.38%), multi-target drugs (2.45%), anti-Amyloid agents (13.30%), anti-Tau agents (2.03%), natural products and derivatives (25.58%), novel drugs (8.13%), novel targets (5.66%), other (old) drugs (11.77%), anti-inflammatory drugs (1.20%), neuroprotective peptides (1.25%), stem cell therapy (1.85%), nanocarriers/nanotherapeutics (1.52%), and others (<1% each).

Expert opinion: Unsuccessful outcomes in AD therapeutics are attributed to pathogenic misconceptions, erratic procedures in drug development and inappropriate regulations. Recommendations for the future are as follows: (i) the reconsideration of dominant pathogenic theories, (ii) the identification of reliable biomarkers, (iii) the redefinition of diagnostic criteria, (iv) new guidelines for disease management, (v) the reorientation of drug discovery programs, (vi) the updating of regulatory requirements, (vii) the introduction of pharmacogenomics in drug development and personalized treatments, and (viii) the implementation of preventive programs.

KEYWORDS:

• Alzheimer’s disease
• treatment
• pharmacological categories
• anti-Aβ treatments
• anti-tau treatments
• immunotherapy
• natural products
• novel targets
• pharmacogenetics

Article highlights

• There was a 30% increase in AD-related scientific publications (over 40,000 papers in total) in the previous 5 years (2008–2012).

• About 20% of the scientific contributions (8,380 papers) were associated with AD treatment (drug discovery, drug development, clinical trials).

• The most frequently investigated pharmacological categories were natural products (25.58%), anti-Amyloid agents (13.30%), old (AD-unrelated) drugs (11.77%), neurotransmitter enhancers (11.38%), novel drugs (8.13%), multi-target drugs (2.45%), anti-Tau agents (2.03%), stem cell therapy (1.85%), nanocarriers/nanotherapeutics (1.52%), neuroprotective peptides (1.25%), anti-inflammatory drugs (1.20%), and others (<1% each).

• Over 100 novel targets (5.66% papers) for AD treatments have been proposed.

• There is a growing interest in the pharmacogenetics of AD.

• The author recommends a) the reconstruction of the dominant pathogenic theories and identification of reliable biomarkers, b) the redefinition of diagnostic criteria and elaboration of more specific guidelines for disease management, c) the reorientation of drug discovery programs and updating of regulatory requirements for drug development, d) the introduction of personalized treatments (pharmacogenomics), and e) the implementation of preventive programs.

Acknowledgments

The author would like to thank Iñaki López, Pablo González, Adam McKay, and Pablo Cacabelos for technical assistance and database mining.

Declaration of interest

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

Additional information

Funding

This manuscript has not been funded.