VIRTICI LLC — Department of Health and Human Services SBIR Phase I: NIDCR

Description

Project Summary Our goal is to develop a novel L lactis probiotic based therapeutic for the treatment of Sj grenandapos s Syndrome SjS SjS is a progressive chronic autoimmune disease characterized by inflammatory cell infiltration of the salivary and lacrimal glands resulting in acinar epithelial cell atrophy cell death and loss of exocrine function It is a debilitating disease affecting as many as million individuals in the US with women being nine times more likely to be afflicted with SjS than men Treatment of SjS remains a significant unmet medical need Current treatment relies on replacement therapies such as artificial saliva and eye lubricants or immunosuppressive agents Because of the multiple antigens involved in this disease process i e fodrin ribonuclear protein Ro SSA La SSB and M R oral tolerance methods become problematic Thus the capacity to stimulate regulatory cells independent of knowing the antigen specificity for the disease poses as an attractive therapeutic device Originally conceived as a diarrheal vaccine for humans we found colonization factor antigen I CFA I from human enterotoxigenic E coli ETEC is potently effective in preventing and treating experimental models for multiple sclerosis and arthritis In fact purified CFA I fimbriae when given orally or nasally and administered in lieu of live Salmonella CFA I as a source of fimbriae can effectively attenuate inflammation without the associated side effects from Salmonella To avoid efforts and costs associated with producing sufficient quantities of recombinant fimbriae we have successfully engineered a Lactococcus lactis strain to express CFA I fimbriae L lactis CFA I Retaining its inhibitory activity L lactis CFA I can protect against collagen induced arthritis CIA and experimental autoimmune encephalomyelitis EAE More importantly our preliminary data now shows L lactis CFA I reverses genetically induced SjS Based on these findings our goal is to develop L lactis CFA I as an oral therapeutic to arrest SjS ! This application is focused on measuring the efficacy PK PD and safety of VTC CFA to support further product development The specific aims are to produce sufficient amounts of VTC CFA and establish analytical and bioactivity assays determine the pharmacokinetics PK and optimal oral dosing of VTC CFA in mice and establish the acute toxicology and MTD profiles for VTC CFA in mice Successful commercialization of VTC CFA would ultimately provide a profound front line medical advancement in the treatment of SjS Project Narrative Sj grenandapos s Syndrome SjS is a progressive chronic autoimmune disease characterized by inflammatory cell infiltration of the salivary and lacrimal glands resulting in acinar epithelial cell atrophy cell death and loss of exocrine function It is a debilitating disease affecting as many as million individuals in the US with women being nine times more likely to be afflicted with SjS than men This project aims to develop a novel L lactis probiotic bacteria expressing colonization factor antigen I CFA I for the treatment of SjS Successful commercialization would ultimately provide a profound front line medical advancement in the treatment of SjS