An international study involving 26 researchers from several institutions including the University of Melbourne has revealed that the iron chelating drug deferiprone worsens cognitive function in individuals with early Alzheimer’s disease. This unanticipated finding indicates that lowering brain iron levels with deferiprone is maladaptive for Alzheimer’s patients.
Alzheimer’s disease is one of the biggest health issues in the world and available treatments are quite basic. Iron deposition in the brain is linked to Alzheimer’s disease therefore, identifying molecules that can reduce iron levels has become an area of interest. Deferiprone, an oral iron chelating agent that is capable of penetrating the blood-brain barrier, was proposed to ameliorate neuroadaptation by lowering brain iron concentrations.
Deferiprone in Alzheimer’s Disease: In the study titled, “Safety and Efficacy of Deferiprone for Treating Iron-Related Cognition Decline in Alzheimer’s Disease: A Randomized Clinical Trial,” the authors report the findings of phase 2, double-masked, placebo-controlled randomized clinical trial to determine the impact of deferiprone on the rate of cognition change and the levels of brain iron in subjects with amyloid-confirmed mild cognitive impairment or early Alzheimer’s disease.
Participants were randomized in a 2:1, and the subject was assigned to either active treatment, that is deferiprone at a dose of 15 mg/kg twice a day, or placebo for 12 months. The main variable was cognitive function which was assessed by using a Neuropsychological Test Battery for memory, executive function, and attention.
Secondary outcomes of the study included changes in the brain iron concentration using quantitative susceptibility mapping magnetic resonance imaging (QSM MRI), changes in brain volume, and side effects. The analysis showed that participants who took deferiprone had a higher rate of cognitive deterioration than those of the placebo group. The reduction was mostly seen in executive function tests.
Deferiprone treatment was effective in the reduction of iron levels in the hippocampus, which was evidenced by QSM MRI. Surprisingly, reduction in iron stores did not reduce hippocampal atrophy but was associated with greater atrophy in frontal brain regions. The incidence of neutropenia, defined as a neutrophil count below 1.5 x 10^9/L, was also higher in the deferiprone group than in previous similar studies.
These results prompt concerns about the safety of deferiprone treatment in this patient group. Altogether these results do not support the idea that iron chelation is a treatment benefitting Alzheimer’s disease and imply that there are multiple roles of iron in neurodegenerative processes. More effort on the research about the effects of alteration in the iron levels in Alzheimer’s and the other forms of treatment needs to be done.
References: Ayton S, Barton D, Brew B, et al. Deferiprone in Alzheimer Disease: A Randomized Clinical Trial. JAMA Neurol. Published online November 04, 2024. doi:10.1001/jamaneurol.2024.3733
