TY - JOUR
T1 - Disease-modifying therapies for tauopathies: agents in the pipeline
AU - Panza, Francesco
AU - Imbimbo, Bruno P.
AU - Lozupone, Madia
AU - Greco, Antonio
AU - Greco, Andrea
AU - Seripa, Davide
AU - Logroscino, Giancarlo
AU - Daniele, Antonio
AU - Colosimo, Carlo
PY - 2019
Y1 - 2019
N2 - Introduction: Tauopathies are heterogeneous clinicopathological entities characterized by abnormal neuronal and/or glial inclusions of the microtubule-binding protein tau. Primary tauopathies considered to be diseases correspond to a major class of frontotemporal lobar degeneration (FTLD) neuropathology (FTLD-Tau), including several forms of frontotemporal dementia (FTD) clinical syndromes. Little progress has been made in the past 20 years in developing effective disease-modifying drugs for primary tauopathies and available symptomatic treatments have limited efficacy. Areas covered: Potential disease-modifying drugs in clinical development to slow neuropathological progression of primary tauopathies. Expert opinion: Since the underlying pathology of primary tauopathies consists of abnormal tau protein aggregates, treatments are being developed to interfere with the aggregation process or to promote the clearance of this protein. Unfortunately, disease-modifying treatments remain years away as demonstrated by the recent negative Phase III findings of a tau aggregation inhibitor (LMTM) for treating the behavioral variant of FTD. Further evidence will come from ongoing Phase I/II trials on novel drugs and immunotherapeutics with various targets–prevention of deposition or removal of tau aggregates, inhibition of tau phosphorylation/acetylation, modulation of O-GlcNAcylation, activation of autophagy or ubiquitin-proteasome system pathways, and rescue of selected tau loss of function or suppression of tau gene expression.
AB - Introduction: Tauopathies are heterogeneous clinicopathological entities characterized by abnormal neuronal and/or glial inclusions of the microtubule-binding protein tau. Primary tauopathies considered to be diseases correspond to a major class of frontotemporal lobar degeneration (FTLD) neuropathology (FTLD-Tau), including several forms of frontotemporal dementia (FTD) clinical syndromes. Little progress has been made in the past 20 years in developing effective disease-modifying drugs for primary tauopathies and available symptomatic treatments have limited efficacy. Areas covered: Potential disease-modifying drugs in clinical development to slow neuropathological progression of primary tauopathies. Expert opinion: Since the underlying pathology of primary tauopathies consists of abnormal tau protein aggregates, treatments are being developed to interfere with the aggregation process or to promote the clearance of this protein. Unfortunately, disease-modifying treatments remain years away as demonstrated by the recent negative Phase III findings of a tau aggregation inhibitor (LMTM) for treating the behavioral variant of FTD. Further evidence will come from ongoing Phase I/II trials on novel drugs and immunotherapeutics with various targets–prevention of deposition or removal of tau aggregates, inhibition of tau phosphorylation/acetylation, modulation of O-GlcNAcylation, activation of autophagy or ubiquitin-proteasome system pathways, and rescue of selected tau loss of function or suppression of tau gene expression.
KW - Dementia
KW - aging-related tau astrogliopathy
KW - corticobasal degeneration
KW - frontotemporal dementia
KW - frontotemporal lobar degeneration
KW - primary age-related tauopathy
KW - primary tauopathies
KW - progressive supranuclear palsy
KW - tau protein
KW - Dementia
KW - aging-related tau astrogliopathy
KW - corticobasal degeneration
KW - frontotemporal dementia
KW - frontotemporal lobar degeneration
KW - primary age-related tauopathy
KW - primary tauopathies
KW - progressive supranuclear palsy
KW - tau protein
UR - http://hdl.handle.net/10807/139447
UR - http://www.tandfonline.com/loi/iern20
U2 - 10.1080/14737175.2019.1606715
DO - 10.1080/14737175.2019.1606715
M3 - Article
SN - 1473-7175
VL - 19
SP - 397
EP - 408
JO - Expert Review of Neurotherapeutics
JF - Expert Review of Neurotherapeutics
ER -