A Novel Probiotic for the Treatment of Sjogren's Syndrome

Period of Performance: 08/02/2016 - 07/31/2017


Phase 1 SBIR

Recipient Firm

Virtici, LLC
Principal Investigator


Project SummaryOur goal is to develop a novel L. lactis probiotic-based therapeutic for the treatment of Sjögren's Syndrome(SjS). SjS is a progressive, chronic autoimmune disease characterized by inflammatory cell infiltration of thesalivary and lacrimal glands, resulting in acinar epithelial cell atrophy, cell death, and loss of exocrine function1-6. It is a debilitating disease affecting as many as 3.1 million individuals in the US7-8, with women being ninetimes more likely to be afflicted with SjS than men5, 8-9.Treatment of SjS remains a significant unmet medical need. Current treatment relies on replacement therapiessuch as artificial saliva and eye lubricants or immunosuppressive agents10-11. Because of the multiple antigensinvolved in this disease process, i.e., ?-fodrin12-15, ribonuclear protein Ro/SSA12, 16-18, La/SSB 12, 16-17, andM3R17, 19-20, oral tolerance methods become problematic. Thus, the capacity to stimulate regulatory cellsindependent of knowing the antigen specificity for the disease poses as an attractive therapeutic device.Originally conceived as a diarrheal vaccine for humans21-23, we found colonization factor antigen I (CFA/I) fromhuman enterotoxigenic E. coli (ETEC), is potently effective in preventing and treating experimental models formultiple sclerosis24-26 and arthritis27-29. In fact, purified CFA/I fimbriae, when given orally or nasally, andadministered in lieu of live Salmonella-CFA/I as a source of fimbriae, can effectively attenuate inflammationwithout the associated side-effects from Salmonella27. To avoid efforts and costs associated with producingsufficient quantities of recombinant fimbriae, we have successfully engineered a Lactococcus lactis strain toexpress CFA/I fimbriae (L. lactis-CFA/I). Retaining its inhibitory activity, L. lactis-CFA/I can protect againstcollagen-induced arthritis (CIA) and experimental autoimmune encephalomyelitis (EAE). More importantly, ourpreliminary data now shows L. lactis-CFA/I reverses genetically induced SjS. Based on these findings, our goalis 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 productdevelopment. The specific aims are to: 1) produce sufficient amounts of VTC-CFA and establish analytical andbioactivity assays; 2) determine the pharmacokinetics (PK) and optimal oral dosing of VTC-CFA in mice, and3) 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.