Advances in the treatment and management of frontotemporal dementia

ABSTRACT

Introduction

Frontotemporal dementia (FTD) is a complex neurodegenerative disorder, characterized by a wide range of pathological conditions associated with the buildup of proteins such as tau and TDP-43. With a strong hereditary component, FTD often results from genetic variants in three genes - MAPT, GRN, and C9orf72.

Areas covered

In this review, the authors explore abnormal protein accumulation in FTD and forthcoming treatments, providing a detailed analysis of new diagnostic advancements, including innovative markers. They analyze how these discoveries have influenced therapeutic strategies, particularly disease-modifying treatments, which could potentially transform FTD management. This comprehensive exploration of FTD from its molecular underpinnings to its therapeutic prospects offers a compelling overview of the current state of FTD research.

Expert opinion

Notable challenges in FTD management involve identifying reliable biomarkers for early diagnosis and response monitoring. Genetic forms of FTD, particularly those linked to C9orf72 and GRN, show promise, with targeted therapies resulting in substantial progress in disease-modifying strategies. The potential of neuromodulation techniques, like tDCS and rTMS, is being explored, requiring further study. Ongoing trials and multi-disciplinary care highlight the continued push toward effective FTD treatments. With increasing understanding of FTD’s molecular and clinical intricacies, the hope for developing effective interventions grows.

KEYWORDS:

• frontotemporal dementia
• therapy
• TDP-43
• tau
• C9orf72
• GRN
• MAPT
• genetics

Article highlights

• Frontotemporal dementia (FTD) is a complex neurodegenerative disorder with diverse clinical manifestations impacting behavior, language, and motor functions.

• Genetic factors are present in approximately 20-30% of FTD cases, contributing to the disease's complexity and posing challenges for disease management and treatment.

• Accurate biomarkers, including promising blood-based indicators, are vital for early diagnosis and monitoring treatment response.

• Therapies targeting genetic forms of FTD, especially those linked to C9orf72 and GRN variants, are showing significant advancements, demonstrating high levels of pathophysiological engagement.

• Non-invasive neuromodulation techniques such as transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS) are being studied for their potential to provide symptomatic relief and cognitive enhancement in FTD patients.

• FTD management necessitates a multi-disciplinary approach, where teams of neurologists, psychiatrists, therapists, and social workers provide comprehensive, personalized care plans addressing both cognitive and behavioral aspects of the disease.

Declaration of interest

The authors have no other 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 apart from those disclosed.

Reviewer disclosures

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

Additional information

Funding

A Benussi was partially supported by the Fondazione Cariplo (grant n° 2021-1516), and by the Fondation pour la Recherche sur Alzheimer.