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

den Heijer JM, Kruithof AC, van Amerongen G, de Kam ML, Thijssen E, Grievink HW, Moerland M, Walker M, Been K, Skerlj R, Justman C, Dudgeon L, Lansbury P, Cullen VC, Hilt DC, Groeneveld GJ

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.