Interview with Olivier Vanakker, Belgian PXE Researcher
AUGUST 1, 2011
By Kelly Harris, Information and Education Coordinator, PXE International
This article first appeared in the Summer 2011 PXE MicroMemberGram
Olivier Vanakker MD, PhD is a pediatrician and clinical geneticist affiliated with the Connective Tissue Disorders team and the Dysmophology team of the Center for Medical Genetics of the Ghent University Hospital, Belgium. In 2009, he receied the degree of Doctor in Medical Sciences for his thesis "Novel Clinical and Etiopathogenetic Findings in Pseudoxanthoma Elasticum." Main topics involved optimization of molecular analysis in pseudoxanthoma elasticum (PXE) and determination of genotype-phenotype correlations, and identification of a PXE-like syndrome. This PhD thesis was awarded the annual Pfizer award for outstanding thesis in Medical Sciences at the Ghent University.
Kelly Harris: What excited you about research into pseudoxanthoma elasticum, and what has kept you committed to it despite its challenges?
Olivier Vanakker: One of the fascinating aspects of pseudoxanthoma elasticum is that it is a multisystemic disease - skin, eyes, blood vessels - caused by a transporter which is mainly active in the liver. This puzzling relationship, how a transporter in the liver can cause elastic fiber mineralization in tissues in which it is hardly expressed, is a pathophysiological enigma which makes you want to investigate this disease in depth to unravel the mystery. What keeps me committed is very simple: patient contacts. PXE patients, in my experience, are the most committed group of patients to identifying what is going wrong in their disease. In the years I have spent on PXE research so far, it has always amazed me how little reluctance there was for yet another examination, yet another blood sample. This is truly unique and makes it a lot easier to study the clinical features and pathophysiological characteristics of pseudoxanthoma elasticum. As a physician, patient contact keeps me aware of the reason we are doing this research: to give patients better health care and, if all goes well, a treatment to stabilize or cure their disease.
KH: What has been your biggest accomplishment?
OV: This is a difficult question; it somehow forces me to brag about my work, which I do not really like to do. I guess that the identification of the PXE-like syndrome, resembling PXE but caused by a defect in an enzyme in the vitamin K cycle, opened up the spectrum of PXE-like diseases and introduced vitamin K and vitamin K-dependent mineralization inhibitors in the field of pseudoxanthoma elasticum. Since then, these proteins, such as matrix gla protein, have been studied by us and others extensively in PXE. Showing that PXE patients are vitamin K deficient and have similar defective inhibitors of mineralization as in the PXE-like syndrome has provided evidence that these proteins are important in this spectrum of ectopic mineralization disorders. The vitamin K deficiency led to the possibility of treatment via vitamin K substitution. Though we know now that it might not be as simple as taking a pill with vitamin K orally, this vitamin still has a lot of potential both in the pathophysiology and treatment of pseudoxanthoma elasticum.
KH: Looking into the future, what are you hoping to pursue with PXE?
OV: From the clinical perspective, treatment has obviously become an important goal. This includes symptomatic treatment, such as anti-VEGF antibodies for the eye symptoms, but also a systemic treatment that would stabilize the disease. Curing it might not be feasible within the next few years; stabilization in a safe and patient-friendly way however should certainly be our objective. Secondly, we need to find molecular markers which make it possible to better predict the clinical evolution of the disease in an individual patient, the so-called modifier genes. This will help us to tailor health-care much more precisely to the patientsʼ needs. Though it will certainly not be easy to find such clinically useful parameters, some promising advances have been made in this field. From a pathophysiological perspective, the relation between the ABCC6 transporter and the mineralization needs to be clarified. I am not sure if we need to pursue identification of the ABCC6 substrate for this, as it has already been proven to be fairly difficult. We do need to identify the pathways leading to mineralization and the mechanisms that cause it and start from there to find clues and targets for alternative treatment options.
KH: When the next PXE research meeting convenes in five years, what are you hoping will have been accomplished?
OV: I would certainly hope that some pathophysiological pathways in pseudoxanthoma elasticum have been unraveled, so that we know better which cellular mechanisms are leading to ectopic mineralization. These may be valuable targets for therapy. We will probably have some preliminary data on various treatment regimes which will be tested in the next years. Secondly, I hope we have obtained a set of modifiers to predict to some extent the course of the disease and which can help us in the day-to-day care for patients. Finally, I hope that the characterization of the spectrum of PXE-like disorders has improved, as these diseases, both on a clinical and pathophysiological level can provide us with valuable information regarding PXE itself.
KH: Thank you very much for your time!