Tau immunotherapies: Lessons learned, current status and future considerations

Area of Science:

• Neuroscience
• Immunology
• Pharmacology

Background:

• Alzheimer's disease (AD) and tauopathies are characterized by tau protein pathology.
• Tau pathology correlates more strongly with dementia severity than amyloid-beta (Aβ) pathology.
• Targeting tau offers a promising therapeutic strategy for improving cognition in AD and other neurodegenerative disorders.

Purpose of the Study:

• To review the landscape of clinical trials for tau-targeting therapies.
• To discuss the complexities and challenges in developing tau immunotherapies compared to Aβ therapies.
• To assess the potential efficacy and optimism surrounding current tau-based clinical trials.

Main Methods:

• Review of current clinical trials focusing on tau immunotherapies.
• Analysis of the differences between mouse and humanized antibodies used in trials.
• Discussion of factors influencing the ideal properties of therapeutic antibodies for tauopathies.

Main Results:

• The majority of tau-targeted clinical trials employ immunotherapies, primarily humanized antibodies.
• Significant complexities exist in tau therapy development, including antibody properties and their impact, which are not fully understood.
• Despite challenges, there is optimism for potential functional benefits in patients with tauopathies.

Conclusions:

• Tau immunotherapies represent a major focus for treating Alzheimer's disease and tauopathies.
• The development of effective tau therapies is complex, requiring careful consideration of antibody characteristics.
• Ongoing clinical trials hold promise for delivering functional benefits to patients suffering from neurodegenerative tauopathies.