• Research priorities: Diagnostic tests
  • Country: Brazil
  • Budget: € 51,652 | Project number: 706.18.39
  • Duration: February 2018 - July 2024
  • Status: Ongoing

Two variants in the LRRK2 gene were found to be strong candidates to control leprosy susceptibility in a unique family affected by leprosy. By infecting macrophages in vitro with M. leprae, this genetic susceptibility will be further studied.

Functional analysis of candidate variants in the early-onset leprosy phenotype using a novel cellular model

Project Coordination

Pontifical Catholic University of Parana, Brazil (PUCPR)


  • Federal University of Piaui, Brazil (UFPI)
  • University of Sao Paulo, Brazil (USP)
  • McGill University, Canada

Project summary

Leprosy is an ancient disease and still is a public health problem in South American, African and Asian countries, in which around 200,000 new individuals are affected every year. Over the past decades, intensive research has resulted in strong evidence for the existence of an innate, genetic component controlling susceptibility to leprosy; however, the exact mechanisms involved is not yet fully understood. In previous studies by the investigator, the entire genome of members of a family presenting a rare leprosy case was sequenced: the disease manifested in two twin sisters at the very early age of 22 months. Also, their father and grandmother were affected, the only unaffected member was the mother. Complex computational analysis reveal two variants in a gene named LRRK2 as strong candidates to control leprosy susceptibility in the studied family; interestingly, several previous studies also have shown LRRK2 function in controlling immune response, and previous genetic studies have already associated LRRK2 variants with leprosy. Although the genetic results are promising, functional validation is necessary. In this study, the investigators will obtain and modify cells from the skin of affected and unaffected family members to generate the LRRK2 variants. Next, these cells will be reprogrammed and differentiated into M. leprae cells target, such as macrophages. The macrophages will be infected in vitro with M. leprae and cellular events will be evaluated to inquire how such variants could contribute to leprosy susceptibility. Results may contribute to a better understanding of the molecular basis of the etiology of leprosy.