A Pilot of the Feasibility of Using the Iron-Chelator Deferiprone on Mild Cognitive Impairment

Summary

The investigators propose to conduct a series of N of One (No1) single blinded clinical trials to pilot the feasibility of using the iron-chelator deferiprone on Mild Cognitive Impairment (MCI). Chelation therapy has previously been reported to slow the rate of cognitive decline in Alzheimer's Disease (AD) by 50% in a single human randomized clinical trial.

Timeline

Start

2018-01

Primary completion

2022-04

Completion

2023-04

Publications

• Background Becerril-Ortega J, Bordji K, Freret T, Rush T, Buisson A. Iron overload accelerates neuronal amyloid-beta production and cognitive impairment in transgenic mice model of Alzheimer's disease. Neurobiol Aging. 2014 Oct;35(10):2288-301. doi: 10.1016/j.neurobiolaging.2014.04.019. Epub 2014 May 1.
• Background De Chiara G, Marcocci ME, Sgarbanti R, Civitelli L, Ripoli C, Piacentini R, Garaci E, Grassi C, Palamara AT. Infectious agents and neurodegeneration. Mol Neurobiol. 2012 Dec;46(3):614-38. doi: 10.1007/s12035-012-8320-7. Epub 2012 Aug 17.
• Background Fine JM, Renner DB, Forsberg AC, Cameron RA, Galick BT, Le C, Conway PM, Stroebel BM, Frey WH 2nd, Hanson LR. Intranasal deferoxamine engages multiple pathways to decrease memory loss in the APP/PS1 model of amyloid accumulation. Neurosci Lett. 2015 Jan 1;584:362-7. doi: 10.1016/j.neulet.2014.11.013. Epub 2014 Nov 13.
• Background Gavett BE, Vudy V, Jeffrey M, John SE, Gurnani AS, Adams JW. The delta latent dementia phenotype in the uniform data set: Cross-validation and extension. Neuropsychology. 2015 May;29(3):344-52. doi: 10.1037/neu0000128. Epub 2014 Aug 25.
• Background Hughes CP, Berg L, Danziger WL, Coben LA, Martin RL. A new clinical scale for the staging of dementia. Br J Psychiatry. 1982 Jun;140:566-72. doi: 10.1192/bjp.140.6.566.
• Background Nairz M, Schroll A, Sonnweber T, Weiss G. The struggle for iron - a metal at the host-pathogen interface. Cell Microbiol. 2010 Dec;12(12):1691-702. doi: 10.1111/j.1462-5822.2010.01529.x. Epub 2010 Oct 21.
• Background Peters DG, Connor JR, Meadowcroft MD. The relationship between iron dyshomeostasis and amyloidogenesis in Alzheimer's disease: Two sides of the same coin. Neurobiol Dis. 2015 Sep;81:49-65. doi: 10.1016/j.nbd.2015.08.007. Epub 2015 Aug 22.
• Background Royall DR, Palmer RF, Markides KS. Exportation and Validation of Latent Constructs for Dementia Case Finding in a Mexican American Population-based Cohort. J Gerontol B Psychol Sci Soc Sci. 2017 Oct 1;72(6):947-955. doi: 10.1093/geronb/gbw004.
• Background Royall DR, Palmer RF; Texas Alzheimer's Research and Care. Validation of a latent construct for dementia case-finding in Mexican-Americans. J Alzheimers Dis. 2013;37(1):89-97. doi: 10.3233/JAD-130353.
• Background Royall DR, Palmer RF. Ethnicity moderates dementia's biomarkers. J Alzheimers Dis. 2015;43(1):275-87. doi: 10.3233/JAD-140264.
• Background Royall DR, Palmer RF. Thrombopoietin is associated with delta's intercept, and only in Non-Hispanic Whites. Alzheimers Dement (Amst). 2016 Feb 26;3:35-42. doi: 10.1016/j.dadm.2016.02.003. eCollection 2016.
• Background Royall DR, Palmer RF, O'Bryant SE; Texas Alzheimer's Research and Care Consortium. Validation of a latent variable representing the dementing process. J Alzheimers Dis. 2012;30(3):639-49. doi: 10.3233/JAD-2012-120055.
• Background Salkovic-Petrisic M, Knezovic A, Osmanovic-Barilar J, Smailovic U, Trkulja V, Riederer P, Amit T, Mandel S, Youdim MB. Multi-target iron-chelators improve memory loss in a rat model of sporadic Alzheimer's disease. Life Sci. 2015 Sep 1;136:108-19. doi: 10.1016/j.lfs.2015.06.026. Epub 2015 Jul 6.

Drugs

Indications