Mar 24, 2020

Development of disease-modifying drugs for frontotemporal dementia spectrum disorders

Nature Reviews. Neurology
Francesco PanzaBruno P Imbimbo

Abstract

Frontotemporal dementia (FTD) encompasses a spectrum of clinical syndromes characterized by progressive executive, behavioural and language dysfunction. The various FTD spectrum disorders are associated with brain accumulation of different proteins: tau, the transactive response DNA binding protein of 43 kDa (TDP43), or fused in sarcoma (FUS) protein, Ewing sarcoma protein and TATA-binding protein-associated factor 15 (TAF15) (collectively known as FET proteins). Approximately 60% of patients with FTD have autosomal dominant mutations in C9orf72, GRN or MAPT genes. Currently available treatments are symptomatic and provide limited benefit. However, the increased understanding of FTD pathogenesis is driving the development of potential disease-modifying therapies. Most of these drugs target pathological tau - this category includes tau phosphorylation inhibitors, tau aggregation inhibitors, active and passive anti-tau immunotherapies, and MAPT-targeted antisense oligonucleotides. Some of these therapeutic approaches are being tested in phase II clinical trials. Pharmacological approaches that target the effects of GRN and C9orf72 mutations are also in development. Key results of large clinical trials will be available in a few y...Continue Reading

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Mentioned in this Paper

Immunotherapy, Passive
Ewings Sarcoma
GRN gene
Language Disorders
Brain
TATA-Binding Protein Associated Factors
TAF15
Phase 2 Clinical Trials
Oligonucleotides, Antisense
MAPT gene

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