Department of Microbiology and Immunology
Contact Information: Email: email@example.com; Phone: 607-253-4023
Sponsor: National Multiple Sclerosis Society
Grant Number: PP1713
Title: Immune Cell Blockade in the Central Nervous System
Annual Direct Cost: $40,000
Project Period: 09/30/2011-10/01/2012
DESCRIPTION (provided by applicant): Multiple sclerosis (MS) is a debilitating neuroinflammatory disease that involves infiltration of the host's inflammatory immune cells into the central nervous system (CNS). Once in the CNS, these cells attack myelin and cause paralysis, blindness and many other debilitating symptoms. The proposed research aims to use an FDA-approved drug, PEG-ADA, to prohibit immune cells from entering the CNS in an animal model of MS called experimental autoimmune encephalitis (EAE). Like MS, EAE is characterized by infiltration of immune cells into the CNS that result in clinical and pathological manifestations similar to MS.
PEG-ADA has been used to treat patients with adenosine deaminase (ADA) deficiency for almost two decades. Its efficacy in reducing extracellular levels of adenosine is well established and it is well tolerated. We have recently discovered that blocking extracellular adenosine or its receptors inhibits immune cell entry into the CNS and protects mice from developing EAE. A common factor in all MS patients is the CNS pathology caused by infiltrating pathogenic immune cells that induce destruction of myelin. We hypothesize that PEG-ADA will inhibit immune cell entry into the CNS, protect mice from EAE development and ameliorate established EAE. The fact that PEG-ADA is an FDA approved drug provides a solid road map for preclinical and clinical studies without some of the hurdles posed by nonFDA approved drugs. We anticipate that this pilot study can lead to the use of PEG-ADA as a curative treatment for MS patients on a global scale.