Hormone therapy can help reduce cysts in the Drosophila renal tubules, according to Cassandra Millet Purima and Chiara Gambieri.
A hormone commonly associated with the regulation of sleep and wakefulness has been found to reduce cysts in fruit flies, according to Concordia researchers. It is a finding that may affect the way we treat some kidney diseases and reduce the need for a kidney transplant.
In a new paper published in the journal MoleculesAlum Cassandra Millet-Boureima (MSc 19) and Chiara Gamberi, Associate Professor of Biology, write that melatonin has been found to reduce cysts in the renal tubules of fruit flies. These tubes are also found in more complex mammals, including humans, where they are called nephrons. This study, which builds on previous studies by Millett Buraima and Gambre, was co-authored by Roman Rosenkweig and Felix Polliak of BH Bioscience in Montreal.
Researchers hope their findings can be applied to treating people with hereditary polycystic kidney disease that is predominant. ADPKD is a chronic, progressive inherited disease characterized by the growth of dozens of cysts in the nephron. It is incurable and affects approximately 12.5 million worldwide.
Similar big and small
Because the nephron in vertebrates is incorporated into other tissues, the researchers conducted experiments with fruit flies – the common fruit fly.
“Drosophila preserves many components of the renal pathway found in vertebrates and has anatomically isolated renal tubules,” Jambieri explains. “With microdissection, we can isolate tubes and perform biochemical and molecular analysis.”
Researchers have bred fruit flies that carry the Bicaudal C gene mutation. It is known to cause kidney cysts in all types of organisms, from flies to frogs to mice to humans.
Over the course of 18 days, Millet-Boureima gave melatonin to 50 Drosophila and ethanol for a control group. She then dissected the flies and scored their cysts, a process that produces a cystic index. And it found that the melatonin-treated flies had fewer and significantly smaller cysts than the control group. Because Millet-Boureima was skilled at dissecting insects and evaluating recovered renal tubules, she was able to avoid counting bias.
It was also able to distinguish between three separate sections of the Drosophila tubule, each with its own unique function, and to assign the cysts to a specific section. After testing several compounds on the same family of cells, I observed different activity along the tubule. Researchers have realized that they will likely develop a targeted therapy depending on the location of the cysts in a patient’s nephrons.
“Biologically, this has a lot of potential that we will obviously develop,” says Gambieri.
Help without hurting
Although Gambieri says melatonin was not previously used to treat PKD, she believes it holds some hope. PKD is a chronic disease, so treatment cannot include any toxic ingredients. This excludes chemotherapy and anti-neoplastic agents used in oncology, for example. However, melatonin is completely non-toxic and shares certain properties with anti-neoplastic and anti-inflammatory properties.
“We know from oncology that melatonin has two effects when administered with chemotherapy,” Jambieri explains. First, it acts as an adjunct to chemotherapy, which makes it work more effectively against cancer cells. Second, it appears to protect healthy cells from chemotherapy toxicity. Basically, melatonin increases chemotherapy specificity. Hopefully, it will have a similar positive effect when used with an anti-ADPKD drug like tolvaptan, which can damage the liver. “
Researchers are keen to share their results as quickly as possible.
“I hope there will be more research on the drugs we tested and that we get more results that will help the PKD community,” says Millet Buraima.
Read the paper cited: “Cyst Reduction by Melatonin in a New Drosophila Model of Polycystic Kidney Disease.”