January 10, 2018

Post Event Summary of Science Café: Perspectives on PKD

Submitted by Chiara Gamberi, Ph. D.
Affiliate Assistant Professor, Department of Biology, Concordia University

On November 17, 2017 I had the honor and privilege to organize the scientific agenda and moderate the first Science Café on polycystic kidney disease (PKD). The Science Café “Perspectives on PKD” was held in the Dollard-des-Ormeaux Civic Center, close to Montréal, with the support of the Italian Institute of Culture, the Italian Consulate and the PKD Foundation of Canada and the endorsement of Concordia University and the Université de Montréal. A room full of participants who beat the Friday afternoon traffic to support the PKD cause joined in to know more about a disease that is surprisingly little known, despite its affecting 12.5 million people world-wide. To put this number into perspective, 12.5 million people corresponds to the population of the Chinese city of Beijing. PKD is a complex disease that affects multiple organs directly and indirectly and has variable severity in different patients. This variability makes it also very challenging to study and has hindered our advances to understand the precise molecular mechanisms of the disease which remain largely unknown, reducing our effectiveness in disease management. There is no cure for PKD and therapeutic options are limited.

After a reception with live music, food and wine in the truest Italian tradition, the Science Café began with the welcome of Italian Consult General Marco Riccardo Rusconi, the Director of the Italian Institute of Culture Dr. Francesco D’Arelli and the PKD Foundation of Canada Director Jeff Robertson. Presentation from five panelists followed. Luisa Miniaci, patient, Montreal Coordinator of the PKD Foundation and event coordinator presented the perspective of the patient, telling her personal story as well as relying her experience and that of friends carrying the disease. The kidneys are fundamental organs contributing to multiple physiological roles. Thus, their impaired function in PKD patients has a series of far-reaching consequences, including digestive issues and disturbed sleep, which in turn impact metabolism and overall well-being and decrease quality of life. Moreover, cysts can form in multiple tissues, more commonly in the liver and pancreas, but also other organs and affect their functions. Dr. Ahsan Alam, Associate Professor of Medicine and Residency Program Director at McGill University introduced the perspective of the health care provider, illustrating the medical aspects of PKD and its care and discussed life style recommendations for PKD patients as well as how personalized guidance is needed for best disease management, because disease progression varies in patients. Over time cysts grow in number and size and eventually damage the surrounding renal tissue and compete for space with the other internal organs causing, for example, compression and a host of medical issues. The next three panelists presented the perspective of research. Dr. Marie Trudel, Full Professor of Molecular Biology at the Department of Medicine of the Université de Montréal and Director of the Molecular Genetics and Development Unit at the Institut de récherches cliniques de Montréal, explained how studies using mouse models can help dissect the function of the proteins encoded by the PKD1 and PKD2 genes responsible for the majority of the PKD cases and shared some of the technologies that are used in her laboratory to perform genetic assays and monitor the changes in the kidney within the animal that can be used to follow on experimental drug testing. Dr. Elena Torban, Associate Professor of Nephrology at McGill University reported on recently published advances from her laboratory. She discussed that, because cysts form in the nephrons during embryonic development, the ideal therapeutic strategy would target cyst formation as early as possible. She also presented intriguing results that alterations in planar cell polarity, a property of the layers of epithelial cells such as those of the nephrons, influence tubule diameter, yet do not seem to affect cyst formation. These are exciting news, because altered cell polarity is typical of the PKD renal tubules, yet it was unclear how it may contribute to cyst formation. Finally, I shared recent results obtained in my own laboratory using a first-in-kind model of PKD in the fruit fly Drosophila melanogaster. Tiny as they may be, fruit flies have the equivalent of almost all human organs (kidney included) and in easier-to-study streamlined form. Historically, fruit fly research has allowed to resolve core biological processes that were too complex to study in vertebrates, earning six Nobel prizes, the last of which was awarded last month. I showed that the PKD fly model displays hallmarks of PKD that can be used to pinpoint the molecular mechanisms of cyst formation and for drug discovery in record times, due to the short generation time of the fruit fly.

A discussion with the public followed the presentations and extended well beyond the scheduled time of the event. Numerous patients were in attendance and clearly expressed the needs for more information on the practical aspects of managing disease, for the patient themselves and their family members. There is a necessity for knowing more on the available care options and for support to make informed decisions between transplantation and dialysis. Genetic counseling is needed for the patients who desire to have a family, yet feel the responsibility of potentially passing on disease. There was also a technical discussion on the mechanisms of action of some tested drugs, that brought on more specialized talk on the strengths and limitations of current animal models for PKD studies and how to best leverage on the assets and complementarity of all current research strategies to collectively yield results to rapidly and safely translate to the clinic. The students in attendance, some engaged in PKD research themselves, other present to become informed, realized the acute need for PKD research and for the synergic fusion of all the different perspectives to move successfully towards a PKD cure. They realized that cures do not happen overnight but result from rigorous research to identify the best therapeutic strategies. As a researcher and educator myself, I consider that exposure a perfect learning experience.

PKD is complex, both as a disease and to tackle scientifically. Because PKD is chronic, any potential drug must be first carefully vetted for side effects that may arise with its prolonged use, an aspect that would not be as concerning in the case of other ailments such as cancer that instead require short cycles of drug administration. The path ahead is clear: in the patient’s best interest we need maximum dialog between the researchers and clinicians to shed light on the disease mechanisms and conceive effective care protocols and strategic therapeutics. We also need the patient’s active involvement in all decision processes and their commitment to implementing beneficial care protocols. Awareness and support from both patients and citizens are also important to enable this process from basic research all the way to patient care. Can we afford to leave any stone unturned?