Role of endocrine disruptors in clinical and neurological manifestations in Sjögren's Syndrome and efficacy of lipid nanodispersions of insulin and cannabidiol for the treatment of dry eye

• Grant number: 21/07312-4
• Support Opportunities: Regular Research Grants
• Start date: November 01, 2021
• End date: June 30, 2024
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Eduardo Melani Rocha
• Grantee: Eduardo Melani Rocha
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated researchers: Alfredo Ribeiro da Silva ; Ana Carolina Fragoso Motta ; Denny Marcos Garcia ; Fernando Chahud ; Hilton Marcos Alves Ricz ; Renata Fonseca Vianna Lopez

Abstract

Primary Sjögren's Syndrome (PSS) affects the ocular surface, oral health and has systemic manifestations, including neuropathies, independent of other diseases. The pathophysiological causes and mechanisms are poorly understood. Due to the frequency of SSp in the population and the difficulties in diagnosing and treating refractory cases, information on environmental influences, pathophysiology and the therapeutic potential of eye drop with insulin delivery systems (INS) and cannabidiol (CBD) justify this study. The hypotheses are that 1) environmental exposure to endocrine disruptors (ED), present as environmental contaminants in everyday life, produce hormonal imbalance and would be diagnostic markers of SSp, 2) that the deviation in tryptophan metabolism has a pro-inflammatory in the kynurenine pathway and in clinical and neurological manifestations; and finally that 3) The topical ocular use of INS and CBD will have therapeutic benefit in a case-control study. The general objectives are to investigate diagnostic markers potentially involved in the pathophysiology and to test therapeutic alternatives for SS. The specific objectives are a) to identify the role of NDs as risk factors and diagnostic markers in SSp; b) investigate kynurenine plasma metabolites and their relationship to neurological manifestations in SSp; c) determine the safety and efficacy of topical INS and CBD in refractory cases of SSp. Comparisons will be made between patients with SSp, non-SS sicca syndrome (NSS) and controls (n=30/group) regarding ED exposure, neurological manifestations and pathophysiology, and plasma dosages of kynurenine metabolites. They will be cross-sectionally compared by demographic data, lifestyle, clinical examination, evaluation of lacrimal and salivary functions, ED tests in saliva and urine, questionnaires on clinical and neurological signs and symptoms, and plasma levels of metabolites. The clinical study of topical ocular treatment with the aim of evaluating the efficacy and safety of eye drops containing INS or CBD will be carried out with individuals with SSp who meet the inclusion and exclusion criteria, evaluated using one of the eye drops or placebo three times a day for 3 weeks. The measurements of ocular signs and symptoms will be compared between the SSp groups in the pre-and post-treatment conditions with INS, CBD, and placebo (vehicle). With these three objectives, we will seek to know more about the factors involved, the pathophysiology, and therapeutic possibilities in SSp. (AU)