PXE International recently launched an Ideation Challenge seeking evidence favoring one of two prevailing hypotheses for the cause of Pseudoxanthoma Elasticum (PXE). PXE International is a non-profit organization founded in 1995 to promote research and support individuals affected by this rare genetic disorder. We recently spoke with Patrick Terry, PXE’s President, about the Challenge.
Hello Mr. Terry – thank you for joining us today. Many of our readers may not be familiar with pseudoxanthoma elasticum (PXE). What can you tell us about this disease?
Pseudoxanthoma elasticum (PXE) is a rare disease affecting approximately 12,000 people worldwide. It is a recessive genetic disorder with signs and symptoms that mimic many aspects of the normal aging process, but at much younger ages, typically beginning in the second decade of life. Symptoms include macular degeneration, skin wrinkling, mineralization of blood vessels, and cardiovascular disease.
PXE International is a non-profit organization that has achieved a tremendous amount since its founding. Can you talk about the origin and mission of the organization?
Our two children, who were 5 and 7 at the time, were diagnosed with pseudoxanthoma elasticum in 1994. We quickly discovered that, like most rare diseases, there was little research being conducted on the disease and no logical coordination of translational enterprise overall. We were naïve parents, with no science background whatsoever. As an engineer, I responded by learning as much as I could to be able to develop a project logic plan to solve the dilemma of their diagnosis. It was a clear expression of purposeful intent, creativity, and our neuroses as powerless parents.
My wife and I founded PXE International within a few months of the kids’ diagnosis. By January 1995, we began working at night in a research laboratory at Harvard after we completed our normal schedule, and helped to discover the gene. As citizen scientists and co-inventors of the gene discovery, we became patent holders for ABCC6. We were able to convince the other researchers involved to assign their rights over to us and in turn we assigned our rights to PXE International to ‘steward’ the gene through all of the critical phases of basic and translational research. We went on to fully characterize the gene and develop a diagnostic test in a large research consortium.
We also established the first lay-owned and operated blood and tissue biorepository, collecting clinical information and biological samples from thousands of patients and controls. We used the PXE Biobank model to create the open access cross-disease research non-profit entity, Genetic Alliance Registry and BioBank (www.biobank.org). We are currently intensely involved in human clinical trials, assay development, drug screening, animal model research, human epidemiological studies, and in exploring many avenues for potential interventions.
What are your objectives for this Challenge and what motivated you to crowdsource it through InnoCentive?
Given the small number of people with the disease, it has not been the subject of research by pharmaceutical and biotech companies. PXE research has historically been conducted by isolated academic labs, which lack the necessary systematic programs for elucidating the root cause of the disease and identifying proven treatments. While our involvement has certainly helped accelerate coordination and communication, there is clearly a need to go beyond the more traditional exploration into the disease. We would like to tap into InnoCentive's worldwide Solver community to identify correlative evidence that further resolves either of the two prevailing hypotheses for the true pathobiology of the disease.
What are some of the limitations in current PXE research that you’d like to address or overcome in this Challenge?
At the present time, and in the absence of serendipity (which we are not ruling out), the key to making further progress on taming this disease is understanding the pathomechanism which results in the clinical phenotype we observe in PXE. This is a difficult challenge at this point because although we know the causative mutations and functional consequences in ABCC6, we do not know what conjugate this membrane transport protein shuttles out of the cell. Absent identifying the endogenous substrate, it would be most helpful to understand which of the two current hypotheses is correct. Is PXE’s phenotype caused primarily by an active circulating metabolite, or, a tissue-specific dysfunction.
Would you care to elaborate on any of the requirements or criteria that you envision seeing in a winning solution?
Ideally, we would like to see some representative evidence, correlative data, or other testable theorem of which the InnoCentive Solver community may already be aware that can effectively advance ABCC6 transmembrane research for PXE.
How does PXE International expect to use the winning solution(s)? What do you see as next steps?
The PXE International research foundation will review and apply the winning solution in a concerted and transparent manner to advance translational research for the purpose of alleviating the burden of those living with PXE.
Thank you very much for speaking with us, and we truly hope that solutions submitted to this Challenge will advance your goals.