Precision medicine in Parkinson's disease: emerging treatments for genetic Parkinson's disease

被引：68

作者：

Schneider, Susanne A. ^{[1
]}

Alcalay, Roy N. ^{[2
]}

机构：

[1] Ludwig Maximilians Univ Munchen, Dept Neurol, Marchioninistr 15, D-81377 Munich, Germany

[2] Columbia Univ, Dept Neurol, Med Ctr, New York, NY USA

来源：

JOURNAL OF NEUROLOGY | 2020年 / 267卷 / 03期

关键词：

Genetic Parkinson's disease; SNCA; GBA; LRRK2; Kinase inhibitor; Small molecule compounds; Venglustat; Ambroxol; Clinical trial; TORC1; inhibitor; Superprecision medicine; GAUCHER-DISEASE; GLUCOCEREBROSIDASE MUTATIONS; THERAPEUTIC STRATEGY; RISK LOCI; LRRK2; IDENTIFICATION; METAANALYSIS; ASSOCIATION; PENETRANCE; INHIBITORS;

D O I：

10.1007/s00415-020-09705-7

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

In recent years, numerous clinical trials for disease modification in Parkinson's disease (PD) have failed, possibly because of a "one-size-fits all" approach. Alternatively, a precision medicine approach, which customises treatments based on patients' individual genotype, may help reach disease modification. Here, we review clinical trials that target genetic forms of PD, i.e., GBA-associated and LRRK2-associated PD. In summary, six ongoing studies which explicitely recruit GBA-PD patients, and two studies which recruit LRRK2-PD patients, were identified. Available data on mechanisms of action, study design, and challenges of therapeutic trials are discussed.

引用

页码：860 / 869

页数：10

共 64 条

[1]

Abrahams E, 2 BIOM M PERS REPR M

[2]

Analysis Group Inc, 2017, BIOPH PIP INN THER C

[3]

[Anonymous], PREV THER PREV IS DE

[4] LRRK2 inhibitors and their potential in the treatment of Parkinson's disease: current perspectives [J].

Atashrazm, Farzaneh ;

Dzamko, Nicolas .

CLINICAL PHARMACOLOGY-ADVANCES AND APPLICATIONS, 2016, 8 :177-189

[5]

Baptista MAS, 2018, LRRK2 KINASE INHIBIT, DOI [10.1101/390815v1, DOI 10.1101/390815V1]

[6] Advances in GSA-associated Parkinson's disease - Pathology, presentation and therapies [J].

Barkhuizen, Melinda ;

Anderson, David G. ;

Grobler, Anne F. .

NEUROCHEMISTRY INTERNATIONAL, 2016, 93 :6-25

[7] Frequency of Loss of Function Variants in LRRK2 in Parkinson Disease [J].

Blauwendraat, Cornelis ;

Reed, Xylena ;

Kia, Demis A. ;

Gan-Or, Ziv ;

Lesage, Suzanne ;

Pihistrom, Lasse ;

Guerreiro, Rita ;

Gibbs, J. Raphael ;

Sabir, Marya ;

Ahmed, Sarah ;

Ding, Jinhui ;

Alcalay, Roy N. ;

Hassin-Baer, Sharon ;

Pittman, Alan M. ;

Brooks, Janet ;

Edsall, Connor ;

Hernandez, Dena G. ;

Chung, Sun Ju ;

Goldwurm, Stefano ;

Toft, Mathias ;

Schulte, Claudia ;

Bras, Jose ;

Wood, Nicholas W. ;

Brice, Alexis ;

Morris, Huw R. ;

Scholz, Sonja W. ;

Nalls, Mike A. ;

Singleton, Andrew B. ;

Cookson, Mark R. .

JAMA NEUROLOGY, 2018, 75 (11) :1416-1422

[8]

Centogene AG, 2018, CENTOGENE DENALI THE

[9] Mutations in the glucocerebrosidase gene are associated with early-onset Parkinson disease [J].

Clark, L. N. ;

Ross, B. M. ;

Wang, Y. ;

Mejia-Santana, H. ;

Harris, J. ;

Louis, E. D. ;

Cote, L. J. ;

Andrews, H. ;

Fahn, S. ;

Waters, C. ;

Ford, B. ;

Frucht, S. ;

Ottman, R. ;

Marder, K. .

NEUROLOGY, 2007, 69 (12) :1270-1277

[10]

Clark LN, 2009, ARCH NEUROL-CHICAGO, V66, P578, DOI 10.1001/archneurol.2009.54

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