The Effect of Interleukin-1 Antagonists on Brain Volume and Cognitive Function in Two Patients With Megalencephalic
Hafize Emine Sönmez1, Merve Savaş2, Bülbül Aliyeva3
1Kocaeli University Faculty of Medicine, Division of Pediatric Rheumatology, Department of Pediatrics, Kocaeli, Turkey.
Background:
Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a rare leukodystrophy characterized by early-onset macrocephaly and progressive white matter vacuolation. The MLC1 protein plays a role in astrocyte activation during neuroinflammation and regulates volume decrease following astrocyte osmotic swelling. Loss of MLC1 function activates interleukin (IL)-1β-induced inflammatory signals. Theoretically, IL-1 antagonists (such as anakinra and canakinumab) can slow the progression of MLC. Herein, we present two boys from different families who had MLC due to biallelic MLC1 gene mutations and were treated with the anti-IL-1 drug anakinra.
Methods:
Two boys from different families presented with megalencephaly and psychomotor retardation. Brain magnetic resonance imaging findings in both patients were compatible with the diagnosis of MLC. The diagnosis of MLC was confirmed via Sanger analysis of the MLC1 gene. Anakinra was administered to both patients. Volumetric brain studies and psychometric evaluations were performed before and after anakinra treatment.
Results:
After anakinra therapy, brain volume in both patients decreased significantly and cognitive functions and social interactions improved. No adverse effects were observed during anakinra therapy.
Conclusions:
Anakinra or other IL-1 antagonists can be used to suppress disease activity in patients with MLC; however, the present findings need to be confirmed via additional research.
Insights
Anakinra treatment reduced brain volume and improved cognitive function in two boys with Megalencephalic Leukoencephalopathy with Subcortical Cysts (MLC). This suggests IL-1 antagonists may slow MLC progression.
Area of Science:
- Neuroscience
- Genetics
- Immunology
Background:
- Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a rare genetic disorder.
- MLC1 protein dysfunction leads to neuroinflammation via interleukin (IL)-1β signaling.
- IL-1 antagonists are theorized to potentially slow MLC progression.
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