Blepharospasm and strabismus are chronic, debilitating, ocular spastic disorders caused by uncontrolled or unbalanced muscle contraction. The long term objective of this work is to create a therapeutic agent that will ablate cholinergic neurons responsible for the muscle contraction in blepharospasm and strabismus, and to treat humans with these conditions.
The specific aims of this phase I proposal are to produce a hybridoma that secretes monoclonal antibodies against a specific cholinergic, nerve terminal molecule, and to then create an immunotoxin by conjugating the monoclonal antibody to ricin A toxin. When administered, the immunotoxin will become internalized in the cholinergic nerve terminal and kill the cholinergic nerve. This approach has an advantage over present treatments in that fewer treatments will be needed and there may be a permanent cure. There are a number of other related, non-ocular spastic disorders for which this immunotoxin could also be used. This is the first time an immunotoxin has been devised to treat these disorders.
