Cell-based Gene Therapy for Multiple Sclerosis

Period of Performance: 09/30/2009 - 06/30/2010

$308K

Phase 1 SBIR

Recipient Firm

Anergix, LLC
Seattle, WA 98144
Principal Investigator

Abstract

DESCRIPTION (provided by applicant): The long-term goal of this project is to develop a treatment for the autoimmune disease multiple sclerosis (MS) that will suppress the immune system in an antigen-specific manner, has a low potential for serious side effects, and is easy to administer. Current treatments for multiple sclerosis (MS), most of which broadly suppress the immune system, are only partially effective and encumbered by side effects or the necessity for frequent injections that leads to a high degree of non-compliance. Using experimental autoimmune encephalomyelitis (EAE), the putative animal model of MS, Anergix developed an antigen-specific gene therapy treatment, in which fibroblasts, transduced to secrete an encephalogenic peptide, when injected into sick mice, cause a dramatic reduction in relapse rate and a profound decrease in the number of lymphocytes in the brain, as well as an alteration in the cytokine profiles to an anti-inflammatory phenotype. Sequestering the transduced cells within an implantable chamber that allowed diffusion of the peptide epitope enabled the use of an allogeneic cell line for therapy. As Anergix moves this therapy towards the clinic, the specific aims of this SBIR Phase I project are: * to identify overt immune alterations, particularly evidence of an anti-inflammatory response, that can be attributed to our therapy and that can be used in a clinical trial to monitor for safety, * to generate and characterize the MBP peptide-secreting human fibroblasts (MRC5-MBP) that will constitute Anergix's therapy Immune studies will be conducted in the SJL/J EAE model and will investigate myelin antigen-specific proliferation and peptide recall cytokine responses. In vivo bioluminescent imaging of MRC5 cells transduced with the luciferase gene will be used to characterize the proliferation, lifespan and survivability of encapsulated transduced cells and mass spectrometry will be used to measure secreted peptide. At the conclusion of these studies, we will have identified immune parameters that are influenced by our cell-based therapy for the treatment of multiple sclerosis, and also characterized the therapeutic cell line we plan to use in a phase 1 clinical trial (milestone). At this point, we will submit an SBIR Phase II application addressing production of a therapeutic Master Cell Bank, and animal toxicology and tumorgenicity studies using this cell bank. These studies were requested by the FDA during the Anergix pre-IND meeting in November 2007. PUBLIC HEALTH RELEVANCE: Currently available disease modifying therapies (DMTs) for MS have many drawbacks including frequent injections and side effects which have limited their market penetration and led to unusually high non-compliance rates.12,13 More than one-third of MS patients stop taking DMTs within 12-18 months. The low dose antigen specific therapy that Anergix is developing for the clinic promises to reduce side effects, reduce the burden of more frequent treatments, and thereby improve patient compliance, leading to better disease management over the lifetime of the patient.