Sickle cell disease and hemoglobinopathies researchers from Unicamp and King's College London, in the United Kingdom, discussed research and advances in the area on Wednesday (11) and Thursday (12), during the Brazil-UK Workshop on Hemoglobinopathies event, held in the main hall of the Faculty of Medical Sciences (FCM). “The exchange of information was aimed at finding a cure for sickle cell anemia, new medicines and better understanding the pathophysiology of the disease”, said Professor Fernando Costa, coordinator of the Hemoglobin research group at the Hemocentro, alongside researcher Nicola Conran. The group has approximately 40 projects in progress.
The workshop was organized by Nicola Conran, as part of a collaboration signed with King's College London more than ten years ago. The initiative began with two projects, which were supported by Fapesp, and research exchange. “The goal of the partnership is to have a large cohort [group of people who share a common characteristic or experience] of patients with sickle cell anemia. We are now carrying out a lot of research in partnership on genetic modifiers and the pathophysiology of the disease”, revealed Nicola.
According to Fernando Costa, sickle cell anemia is a chronic disease with well-established clinical treatment and which has the Hemocentro as an important reference. Currently, the only possibilities for curing the disease would be bone marrow transplantation or gene therapy, but this is still an alternative available to few patients. “This Unicamp workshop was planned to take place in conjunction with King's College. The two institutions have made relevant discoveries about sickle cell disease. However, what was supposed to be an internal event ended up being a meeting with researchers from various parts of Brazil.”
Public health
One of the most prevalent diseases worldwide, sickle cell disease (which mainly comprises sickle cell anemia and hemoglobin C disease) is considered a serious public health problem. It is believed that, worldwide, around 300 children are born each year with sickle cell disease, the majority in low- and middle-income countries.
Geneticist from the Center for Molecular Biology and Genetic Engineering (CBMEG) at Unicamp Mônica Barbosa de Melo, one of the speakers, said that her research group has been working on complications associated with sickle cell disease. In the case of sickle cell anemia, the cause is a single mutation in the beta-globin gene, in homozygosity.
This mutation causes a change in the shape of the red blood cell. Biconcave, it can take on the shape of a sickle which, throughout oxygenation/deoxygenation events, ends up remaining in this elongated shape, obstructing the capillaries. A great phenotypic variability is observed, which is reflected in the various complications presented by patients. Complications vary from patient to patient, both in number and severity.
“We seek to identify genetic markers that indicate, for example, why a patient presents certain complications and others do not, such as cerebrovascular accident (CVA), retinopathy, leg ulcers, as well as complications during pregnancy. We try to understand the genetic modulators of sickle cell disease", said Mônica.
Placenta
Sickle cell disease can also cause complications during pregnancy. Therefore, Mônica commented that her research group is developing a project that studies pregnant women with sickle cell cells, in cooperation with the Hospital da Mulher – Caism. Obstetricians Maria Laura Costa Nascimento, Mary Angela Parpinelli and Fernanda Surita participate.
"Typically, women with sickle cell disease are at greater risk for pregnancy complications, such as worsening anemia, pain crises, acute chest syndrome, susceptibility to infections, fetal growth restriction and pre-eclampsia, with risks for the mother and the fetus ", explained Monica. “We try to look for genes that indicate the reasons for pregnancy complications. Probably in an environment with reduced oxygenation, the role of oxidative stress and inflammation are important.”
Postgraduate student Letícia Carvalho, who is studying for her doctorate under the supervision of Mônica and co-supervision of Laura Costa, evaluates the placenta of patients with sickle cell disease in this project developed at Caism. In her master's degree, the student analyzed the gene expression profile of the inflammatory pathway and found changes in the expression of some genes. As a result of these findings, she investigated the matter further by creating a transcriptome of the placenta (evaluating all the RNA).
Letícia reported that, to try to identify genes that may be differentially expressed in the placentas of these patients, samples of villi collected from the maternal side of the placenta are obtained shortly after birth and subsequently subjected to RNA (ribonucleic acid) extraction.
After extracting RNA, it takes it for sequencing at the Central Laboratory for High Performance Technologies (LaCTAD), a facility sequencing and other procedures. This laboratory returns the results generated, which are analyzed using bioinformatics tools. "We have already found some differentially expressed genes linked to the oxidative stress pathway", said Letícia.
The results obtained by RNA sequencing could provide important data for a better understanding of how the disease affects the physiology of the placenta and increases the risks of maternal and fetal complications, expanding the possibilities for future studies.
In addition to the project with placentas, there are also other ongoing projects that study retinopathy, leg ulcers and stroke, all in sickle cell patients. The leg ulcer project, for example, aims to identify genetic variants that can be used, in the future, as markers to identify patients with a greater predisposition to developing this complication.
