SOYMEDS INC — Department of Health and Human Services SBIR Phase II: 106

Description

ABSTRACT The difficulties for creating an efficacious oral autoantigen therapy are basically twofold practicality and efficacy Practically most protein autoantigens will be expensive to manufacture to administer and may not remain intact following passage through the gastrointestinal tract Therapeutically even if some of the protein autoantigens survive to interact with immune cells in the Gut Associated Lymphoid Tissue GALT their ability to significantly reduce autoimmune T and B cells responses in patients has not been effectively demonstrated Developing a routine practical strategy for oral autoantigen therapy is certainly a difficult and risky proposition Demonstrating the feasibility of a technology for routine and practical oral autoantigen therapy would be unique As a proof of principle we have expressed an autoantigen the alpha subunit of the human nicotinic acetylcholine receptor as a fusion with the reovirus sigma protein in transgenic soybean seeds The logic behind such an approach lies in the ability of the reovirus sigma protein sigma to bind microfold cells covering mucosal lymphoid tissues Autoantigens fused to sigma target the immunogen to these cells and deliver the autoantigen in a tolerizing context to limit an ongoing autoimmune response Further while such autoantigens and fusion proteins are difficult to manufacture the ability to express large quantities of a sizeable protein and administer it as a consumable soymilk formulation is unique to this platform expression system The autoantigen that we will focus on for these studies is one that most patients with myasthenia gravis mount an immune response against i e the extracelluar portion of the nicotinic acetylcholine receptor alpha chain AChR In this proposal we will manufacture quantities of an AChR sigma concentrate made from transgenic soybean seeds expressing this fusion protein Studies to define manufacturing and encapsulation of this powdered material will be conducted We will also use a rat model to begin to define safety in vivo distribution and therapeutic efficacy using a model of experimental autoimmune myasthenia gravis Completion of these studies will address some of the most important regulatory hurdles for approval of oral soy based concentrates containing this novel fusion protein If successful the therapeutic efficacy studies will suggest that we have developed a candidate oral tolerance therapy for the autoimmune disease myasthenia gravis MG The practical advantages of soybean derived therapeutics combined with the efficacy of delivering an autoantigen in a tolerizing context to the gut immune system represent a novel solution for therapeutic intervention for myasthenia gravis and potentially many other autoimmune diseases Narrative Demonstrating the feasibility of a technology for routine and practical oral autoantigen therapy would be unique We have expressed a candidate oral tolerance therapy for myasthenia gravis using transgenic soybean seeds as the protein expression system The practical advantages of soybean derived therapeutics combined with the efficacy of delivering an autoantigen in a tolerizing context to the gut immune system represent a novel solution for therapeutic intervention for autoimmune diseases