PXE Community and Research Meeting in Belfast
On September 18–19, 2026, members of the PXE community, researchers, family members, and supporters gathered at Queen’s University Belfast in Northern Ireland for two days devoted to learning, discussion, connection, and research.
The meeting brought together two things that are essential to progress in PXE: the lived experience of people with PXE and the scientific work needed to prepare for better treatments and clinical trials.
Watch the recording of the September 18 meeting.
Understanding PXE
The first day began with an overview of pseudoxanthoma elasticum and what has been learned since PXE International was founded more than 30 years ago.
PXE is caused by variants in the ABCC6 gene. Loss of normal ABCC6 function results in reduced circulating inorganic pyrophosphate (PPi), an important inhibitor of unwanted mineralization. The result is progressive mineralization affecting elastic tissues, particularly in the eyes, skin, and vascular system.
In the eye, characteristic findings include peau d’orange and angioid streaks, which reflect changes and breaks in Bruch’s membrane. The most serious vision-threatening complication is choroidal neovascularization. Anti-VEGF therapy has transformed management of this complication and can often preserve vision when abnormal blood vessels are detected and treated promptly.
The discussion also covered vascular manifestations of PXE, including peripheral arterial disease and cerebral small-vessel disease, as well as the risk of gastrointestinal bleeding.
One theme ran through the entire meeting: PXE is extraordinarily variable. Two people with the same disease-causing variants may have very different symptoms and rates of progression. Understanding that variability is one of the major challenges facing PXE research.
The Biomarker Problem
Developing a treatment is only part of the challenge in a slowly progressive rare disease.
Researchers also need reliable ways to determine whether a treatment is working.
Many manifestations of PXE develop over years or decades. Waiting for major changes in vision, vascular disease, or other clinical outcomes would make conventional clinical trials extremely long, large, and expensive. This creates a significant barrier to therapeutic development, particularly for a rare disease with a relatively small potential commercial market.
For that reason, a major focus of current PXE research is identifying and validating biomarkers and clinical outcome measures that change more quickly and reliably than the disease itself.
Among the measures being studied is dark adaptation — how rapidly the eye recovers its ability to see after moving from bright light into darkness. Dark adaptation may provide a sensitive functional measure of changes in the retina before conventional visual acuity measures show substantial change.
Other candidate measures include circulating PPi, vascular assessments, retinal imaging, participant-reported outcomes, and quantitative measures of disease severity.
The goal is not simply to find interesting measurements. It is to establish measures sufficiently reproducible and clinically meaningful to support future interventional trials.
Looking at the Eye in New Ways
Professor Imre Lengyel and colleagues at Queen’s University Belfast described new approaches for studying what happens in the PXE eye.
Calcification in Bruch’s membrane is not simply an inert deposit. Hydroxyapatite crystals can interact with proteins, lipids, and other molecules in the surrounding tissue. Understanding how these deposits alter the environment of the retina may reveal new therapeutic targets.
Researchers are applying increasingly sophisticated imaging technologies to examine these changes.
Adaptive optics can provide extraordinarily detailed images of the retina, in some cases allowing researchers to visualize individual photoreceptor cells and other microscopic structures that cannot be resolved with conventional clinical imaging.
Other advanced imaging approaches may help identify very early changes associated with calcification and retinal dysfunction.
These technologies raise an important possibility: rather than waiting years to observe clinically obvious progression, researchers may eventually be able to detect much smaller biological changes over shorter periods of time.
Research Participation in Belfast
The second day of the meeting moved from discussion to direct research participation.
People with PXE volunteered for a feasibility study at Queen’s University Belfast involving:
specialized eye imaging, collection of tear samples, and other research assessments.
The study is exploring whether these measurements can be collected reliably and acceptably from people with PXE and whether they may provide useful information about inflammation, calcification, and retinal changes.
The feasibility work is important in its own right. Before a measure can be incorporated into a large natural-history study or clinical trial, researchers need to know whether it can be collected consistently, whether participants can reasonably undergo the procedure, and how much the measurement varies.
The Belfast participants therefore contributed not only samples and images, but also practical information about how future PXE studies can be designed.
Building a Longitudinal Picture of PXE
Another major focus of the meeting was the need to understand PXE over time.
A single medical visit provides only a snapshot. For clinical-trial planning, researchers need longitudinal information showing how symptoms, biomarkers, imaging findings, vascular function, and quality of life change within the same individual.
PXE International is developing a broader natural-history and biomarker program designed to bring these different kinds of information together.
The aim is to combine existing historical data with prospective measurements, including biochemical measures such as PPi, functional assessments, participant-reported outcomes, biospecimens, genomic information, and selected clinical measurements.
This work is intended to help answer several fundamental questions:
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Which measures change reliably over time?
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How much do they vary from person to person?
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How much do they vary within the same person?
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Which measures are most closely associated with clinically meaningful disease progression?
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And ultimately, which measures could allow a future clinical trial to determine whether a therapy is having an effect?
Digital Cabinet: Data Controlled by the Individual
Ian Terry demonstrated Digital Cabinet, the participant-centered data infrastructure being used by PXE International.
The premise is simple but important: people should be able to gather and control their own health and research information rather than having it fragmented across hospitals, laboratories, research studies, and incompatible electronic health record systems.
Digital Cabinet can bring together information such as genetic test reports, imaging, clinical records, questionnaires, and research data.
Individuals determine how their information may be used and shared. That creates an infrastructure that can support long-term research without requiring the community to reconstruct its history every time a new study begins.
For a disease like PXE, where meaningful changes may occur over decades, preserving longitudinal information is particularly important.
Participants were encouraged to begin completing the core PXE information in Digital Cabinet, including diagnosis, disease severity, and baseline health information.
PXE and GACI: Related Diseases, Shared Opportunities
The meeting also highlighted the close biological relationship between PXE and generalized arterial calcification of infancy (GACI).
Although the clinical presentations are very different, both diseases involve abnormalities in pathways that normally protect tissues from pathological mineralization. Research across these conditions can therefore be mutually informative.
Collaboration among PXE researchers, GACI researchers, families, and organizations such as the Brighter Hope Foundation may help accelerate understanding of the underlying biology and the development of treatments.
What Comes Next
PXE research has moved a long way from simply identifying the gene responsible for the disease.
The field now has a much clearer understanding of the ABCC6–ATP–PPi pathway, increasingly sophisticated tools for examining calcification and retinal function, new approaches to measuring disease progression, and a community capable of participating directly in longitudinal research.
But an important problem remains.
For therapies to advance efficiently, researchers need credible biomarkers and outcome measures that can demonstrate biological and clinical change within a practical clinical-trial timeframe.
That is why projects such as the Belfast imaging study, dark-adaptation research, PPi studies, longitudinal natural-history work, and Digital Cabinet are connected. Each addresses a different part of the same problem.
The Belfast meeting demonstrated what PXE International has relied upon since its beginning: people with PXE working directly with researchers to build the evidence needed for the next stage of therapeutic development.