An 8-week, open-label, dose-finding study of nimodipine for the treatment of progranulin insufficiency from GRN gene mutations.
Alzheimers Dement (N Y)
; 3(4): 507-512, 2017 Nov.
Article
en En
| MEDLINE
| ID: mdl-29124108
ABSTRACT
INTRODUCTION:
Frontotemporal lobar degeneration-causing mutations in the progranulin (GRN) gene reduce progranulin protein (PGRN) levels, suggesting that restoring PGRN in mutation carriers may be therapeutic. Nimodipine, a Food and Drug Administration-approved blood-brain barrier-penetrant calcium channel blocker, increased PGRN levels in PGRN-deficient murine models. We sought to assess safety and tolerability of oral nimodipine in human GRN mutation carriers.METHODS:
We performed an open-label, 8-week, dose-finding, phase 1 clinical trial in eight GRN mutation carriers to assess the safety and tolerability of nimodipine and assayed fluid and radiologic markers to investigate therapeutic endpoints.RESULTS:
There were no serious adverse events; however, PGRN concentrations (cerebrospinal fluid and plasma) did not change significantly following treatment (percent changes of -5.2 ± 10.9% in plasma and -10.2 ± 7.8% in cerebrospinal fluid). Measurable atrophy within the left middle frontal gyrus was observed over an 8-week period.DISCUSSION:
While well tolerated, nimodipine treatment did not alter PGRN concentrations or secondary outcomes.
Texto completo:
1
Bases de datos:
MEDLINE
Tipo de estudio:
Diagnostic_studies
/
Prognostic_studies
Idioma:
En
Revista:
Alzheimers Dement (N Y)
Año:
2017
Tipo del documento:
Article
País de afiliación:
Canadá