Anti-leukocyte recruitment therapy for the treatment of seizures and epilepsy
Inventors
Fabene, Paolo Francesco • Butcher, Eugene C. • Constantin, Gabriela
Assignees
US Department of Veterans Affairs • Leland Stanford Junior University
Publication Number
US-7682613-B2
Publication Date
2010-03-23
Expiration Date
2027-06-06
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Abstract
Methods are provided for the prevention and treatment of seizures and epilepsy. It is shown herein that leukocyte recruitment plays a key role in the pathogenesis of epilepsy. Treatment with an agent that inhibits leukocyte recruitment has therapeutic and preventative effects in blocking recurrent seizures and epilepsy.
Core Innovation
Methods are provided for the prevention and treatment of seizures and epilepsy. It is shown herein that leukocyte recruitment plays a key role in the pathogenesis of epilepsy. Treatment with an agent that inhibits leukocyte recruitment has therapeutic and preventative effects in blocking recurrent seizures and epilepsy.
It is shown herein that inhibition of leukocyte recruitment through a variety of adhesion molecules interferes with the pathogenesis of epilepsy, where the exemplary adhesion molecules include VLA-4; VCAM-1, LFA-1, ICAM-1 and PSGL-1. Therapeutic agents block the interaction between leukocytes and adhesion molecules present on endothelial cells, including integrins, selectins, and mucins. Blocking adhesion molecules involved in leukocyte trafficking present on leukocytes or endothelial cells prevents seizures and development of epilepsy.
Leukocyte recruitment involves interactions between endothelial cell adhesion molecules and leukocyte ligands, including selectins, ICAM, VCAM on endothelial cells and integrins, L-selectin, PSGL-1 on leukocytes. Blockade of these adhesion molecules, or chemokine signaling involved in leukocyte trafficking, inhibits leukocyte recruitment to the CNS. This inhibition has been demonstrated to have therapeutic and preventive effects on seizures and epilepsy in animal models, thus providing a novel treatment approach.
Claims Coverage
The patent includes one independent claim focusing on a method of preventing seizures using an antibody specific for α4 integrin. This claim defines the main inventive feature relating to inhibiting seizure recurrence through targeted leukocyte adhesion molecule blockade.
Use of antibody specific for α4 integrin to prevent seizure recurrence
A method of preventing seizures in an individual mammal that has epilepsy, comprising administering an effective amount of an antibody specific for an α4 integrin to inhibit the recurrence of seizures.
The claim focuses on the inventive feature of using α4 integrin-specific antibodies to inhibit leukocyte recruitment and thereby prevent seizures in epileptic individuals.
Stated Advantages
Therapeutic and preventative effects in blocking recurrent seizures and epilepsy by inhibiting leukocyte recruitment.
Dramatic reduction of visible convulsions and seizure frequency in animal models treated with anti-adhesion molecule agents.
Preservation or improvement of cognitive behavior in treated animals compared to untreated epileptic controls.
Preventive administration completely blocks seizures and development of epilepsy in animal models.
Documented Applications
Treatment and prevention of seizures and epilepsy in mammals, including humans.
Use of antibodies and agents that block leukocyte recruitment for therapeutic intervention in epilepsy.
Potential clinical applications in preventing epilepsy following brain insults associated with inflammation such as traumatic brain injury.
Interested in licensing this patent?