ICE/caspase 1 inhibitors and IL-1beta receptor antagonists as potential therapeutics in epilepsy.
Epilepsy is a disabling neurological disorder that is characterized by recurring, unprovoked seizures. Drug-resistant epilepsy affects approximately 30% of individuals with epilepsy; thus, one of the main challenges for epilepsy therapy is the development of alternative anticonvulsant approaches. The discovery that inflammatory mediators contribute significantly to the onset and recurrence of seizures in experimental models, as well as the presence of inflammatory molecules in human epileptogenic tissue, highlight the possibility of targeting specific inflammation-related pathways to control seizures that are otherwise resistant to the available anti-epileptic drugs. This review summarizes the proof-of-principle evidence, obtained in experimental disease models, demonstrating the anticonvulsant activity of specific anti-inflammatory drugs, such as inhibitors of IL-1-converting enzyme/caspase 1 and antagonists of IL-1beta receptors. Drugs that block IL-1beta actions have entered clinical trials as potential therapeutics for autoimmune and inflammatory pathologies, and may also have therapeutic potential in epilepsies associated with proinflammatory processes in the brain.
Vezzani
Annamaria
A
Mario Negri Institute for Pharmacological Research, Laboratory of Experimental Neurology, Department of Neuroscience, Via Giuseppe La Masa 19, 20156 Milano, Italy. vezzani@marionegri.it
Balosso
Silvia
S
Maroso
Mattia
M
Zardoni
Daniela
D
Noé
Francesco
F
Ravizza
Teresa
T
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology / Q000627:therapeutic use*; D061945:Caspase Inhibitors; D004351:Drug Resistance; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D004827:Epilepsy / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000473:pathology; D053583:Interleukin-1beta / Q000378:metabolism* / Q000502:physiology; D053573:Receptors, Interleukin-1 Type I / Q000037:antagonists & inhibitors*
D000927:Anticonvulsants; D061945:Caspase Inhibitors; D004791:Enzyme Inhibitors; D053583:Interleukin-1beta; D053573:Receptors, Interleukin-1 Type I