A randomized single and multiple ascending dose study in healthy volunteers of LTI-291, a centrally penetrant glucocerebrosidase activator

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作   者：

den Heijer, Jonas M.;  Kruithof, Annelieke C.;  van Amerongen, Guido;  de Kam, Marieke L.;  Thijssen, Eva;  Grievink, Hendrika W.;  Moerland, Matthijs;  Walker, Mike;  Been, Kees;  Skerlj, Renato;  Justman, Craig;  Dudgeon, Lindsay;  Lansbury, Peter;  Cullen, Valerie C.;  Hilt, Dana C.;  Groeneveld, Geert Jan; 

作者机构：

Netherlands;  Kent;  MA USA;  Canterbury CT2 7FG;  Ctr Human Drug Res;  England;  Lysosomal Therapeut Inc;  Certara QSP;  NL-2333 CL Leiden;  Zernikedreef 8;  Cambridge; 

关键词：

clinical trial;  phase 1;  Parkinson'  GBA;  s disease;  disease modification; 

期刊名称：

British Journal of Clinical Pharmacology

i s s n：

0306-5251

年卷期：

2021 年 87 卷 9 期

页   码：

3561-3573

页   码：

摘   要：

Aims A mutation in the GBA1 gene is the most common genetic risk factor for developing Parkinson's disease. GBA1 encodes the lysosomal enzyme glucosylceramidase beta (glucocerebrosidase, GCase) and mutations decrease enzyme activity. LTI-291 is an allosteric modulator of GCase, enhancing its activity. These first-in-human studies evaluated the safety, tolerability, pharmacokinetics and pharmacodynamics of single and multiple ascending doses of LTI-291 in healthy volunteers.