Chemical Name: 3-(2-methoxyethyl) 5-propan-2-yl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate
Therapy Type: Small Molecule (timeline)
Target Type: Metals
Condition(s): Frontotemporal Dementia
U.S. FDA Status: Frontotemporal Dementia (Phase 1)
Approved for: Subarachnoid hemorrhage
Nimodipine is a calcium channel blocker. It is prescribed to prevent vasospasm and possible subsequent stroke in people who have suffered a hemorrhage in the subarachnoid space, the compartment surrounding the brain.
The rationale in evaluating nimodipine capsules in frontotemporal dementia is that it is believed to increase levels of progranulin (see 2012 New York Times story). Plasma and CSF concentrations of this protein are reduced in carriers of pathogenic progranulin mutations, which generally cause progranulin haploinsufficiency and constitute a major genetic cause of FTD (Finch et al., 2009).
In 2013 and 2014, a pilot trial at the University of California, San Francisco, evaluated nimodipine in eight symptomatic and asymptomatic carriers of loss-of-function mutations in the gene for progranulin. Participants first take escalating doses of nimodipine for a period of four weeks, then the maximum tolerated dose for another four weeks, and then undergo one week of tapering off. This open-label trial aims primarily to determine the maximum tolerated dose of nimodipine in this patient population as preparation for further efficacy trials. Secondary outcome measures of the trial include plasma progranulin levels measured throughout the trial, CSF progranulin levels measured twice, plasma and CSF cytokine levels, and brain MRI scan. For details, see clinical trials.gov.
- Finch N, Baker M, Crook R, Swanson K, Kuntz K, Surtees R, Bisceglio G, Rovelet-Lecrux A, Boeve B, Petersen RC, Dickson DW, Younkin SG, Deramecourt V, Crook J, Graff-Radford NR, Rademakers R. Plasma progranulin levels predict progranulin mutation status in frontotemporal dementia patients and asymptomatic family members. Brain. 2009 Mar;132(Pt 3):583-91. PubMed.