Selective Inhibition of Platelet GPIb-alpha Binding to Leukocyte Mac-1 as a Therapeutic for Multiple Sclerosis

ABSTRACT The principal overall objective of this project is the development of novelsafer and more effective therapy for Multiple SclerosisMSspecifically a monoclonal antibodymAbthat disrupts the interaction between leukocytesMacand plateletsGPIbwhich have been implicated in the pathophysiology of MSMS is a chronic inflammatory disease of the CNSaffecting approximatelymillion people worldwidein which lymphocytes cross the blood brain barrier and attack the myelin sheath of neurons in the brain and spinal cordCurrently approved medications for MS do not have disease modifying capabilitiesand have significant safety and tolerability issuesAccordinglythe biggest unmet medical need in the MS field is to find a therapy that would provide either neuroprotection and or preserve myelinand slow or halt disease progressionIn the application Sujana Biotech plans to translate previous pioneering work by its scientific foundersDrsDan Simon and Ed Plowdefining the precise points of interaction between a leukocyte expressed integrin and a platelet expressed glycoprotein counter receptorThis research not only identified the specific amino acids that mediating binding but also demonstrated that it is possible to selectively inhibit leukocyte platelet interaction without interfering with other critical interactionsincluding those that mediate normal hemostasisPreliminary studies by the applicantsusing polyclonal antibodies directed against Macon leukocytesprovided preclinical evidence of efficacy in the EAE model of MSIn additionplatelets have been found in human chronic active MS lesions and increased platelet activation was demonstrated in the peripheral blood of MS patientsThe proposed studies are a logical extension of our previous studies testing an anti Machumanized mAb as a viablenovel treatment for MSWe will examine the effects of the mAb in the EAE model of MSThe specific aims of this proposal areEvaluate selectivity of anti MacmAb in binding to Gp bblocking platelet leucocyte interactionandEvaluate in vivo efficacy of anti MacmAb in the EAE modelThe long term goal of this project is to develop a novelpotent anti Machumanized mAb as a more effective and safer medicine than current treatments for MSwhich will slowdown or potentially halt disease progression Narrative Multiple SclerosisMSis a commonchronic inflammatory demyelinating disease of the central nervous systemCurrent drugs relieve the symptoms but do not cure the diseaseThe goal of this project is to identify and test a newpotentinjectable humanized monoclonal antibody that prevents the interaction between blood platelets and white blood cellsand by this mechanism will provide neuroprotection and greater medical benefit and less side effects than current medicines for millions of patients at with MS