At Orfenix, our mission is to develop therapies for unmet medical needs. One such need is a treatment for pseudoxanthoma elasticum (PXE), a rare genetic disorder that significantly impacts patients’ lives. Heleen van Loenen, head of the Dutch PXE patient organisation, is an expert in PXE and has a deep understanding of its impact on patients. We spoke with her about the condition, its burden for patients, common misconceptions about PXE, the importance of raising awareness, and the need to develop treatments.
What is PXE and what symptoms do patients typically develop?
PXE is a rare inherited condition that affects the body’s connective tissue. It leads to the gradual hardening (calcification) and breakdown of elastic fibers, which normally keep organs like the skin and blood vessels flexible. The calcification seen in PXE mainly impacts the skin, eyes, and cardiovascular system:
- Skin: Progressive calcification in the skin leads to small, yellowish bumps (papules) typically appearing on the neck, underarms, and other flexural areas. Over time, the skin may become loose and wrinkled.
- Eyes: Calcification in the eyes, specifically at the Bruch’s membrane, results in angioid streaks and choroidal neovascularization (abnormal blood vessel growth). Over time, these eye changes can cause central vision loss and other visual problems.
- Cardiovascular system: Arterial calcifications, or the hardening of blood vessels, are a hallmark of PXE. Symptoms range from mild hypertension to severe complications such as ischemic stroke and peripheral artery disease.
PXE symptoms differ per patient and present in an unpredictable order. Severe visual impairment, legal blindness, peripheral arterial disease, ischemic stroke and vascular dementia are considered major causes of morbidity in PXE. However, other symptoms can also seriously impact patients’ lives. For example, muscle pain due to poor blood flow (intermittent claudication) can impair their ability to practice sports or walk longer distances. Typically, PXE has a late onset (from about 45 years of age) and progresses over time.
How do PXE patients and their family caregivers experience the disease burden?
The unpredictable onset and wide variety of PXE symptoms, as well as the similarity of some symptoms to symptoms of aging, often makes it challenging for patients to distinguish what is PXE-related. Combined with the slow progression of the disease, patients often underestimate the severity of their condition; they grow accustomed to the symptoms and may not realise the seriousness of their condition until it is far advanced. Heleen van Loenen illustrates the impact of PXE by simply counting the number of hospital events PXE patients experience per year and comparing this to the number of events non-patients of the same age experience annually. This simple arithmetic confronts patients with the major impact PXE has on their lives.
Family caregivers often have a much clearer view of disease progression. Heleen van Loenen shared an example of a patient who was gradually losing his vision. The patient expressed to his ophthalmologist that his family complained he was always tired yet worked full-time. It took an intervention from the ophthalmologist for the patient to realise his persistent exhaustion was linked to his condition.
The mental consequences of a PXE diagnosis can be heavy. Patients and their family caregivers struggle with the uncertainty of what lies ahead and how it will impact their lives. PXE symptom development varies from person to person, making the future unpredictable for each patient. For example, one patient who ran a hotel with her husband was worried about when the disease would impair her ability to work and the subsequent impact on their business. The uncertain future adds a further mental burden to the suffering caused by this debilitating disease.
What are some misconceptions about PXE?
A common misconception is that PXE symptoms are merely signs of aging. Additionally, PXE patients often struggle to recognize their symptoms and appear normal to the outside world. Consequently, those around them may fail to recognise the condition and do not realize that the person is suffering from issues such as severely impaired vision or inability to walk long distances due to intermittent claudication.
What are the challenges for medical caregivers when it comes to PXE?
/Unfortunately, PXE is easily misdiagnosed and mistreated due to its rarity, slow progression, and wide variety of symptoms with unpredictable order of presentation. PXE affects approximately 20,000 people worldwide, including 400 in the Netherlands. Many medical caregivers are unfamiliar with PXE. Consequently, patients can suffer through a long and frustrating journey to diagnosis. One member of the PXE patient organization shared he spent almost 20 years before receiving the correct diagnosis.
Once PXE is suspected, Dutch patients are referred to the Utrecht Expertise Center for Pseudoxanthoma Elasticum (UECP). The UECP has developed an extensive questionnaire assessing known symptoms of PXE. The wide variety of symptoms and their gradual progression make it challenging to pinpoint PXE as causative. For example, neck stiffness was recently suggested to potentially be more frequent in PXE patients, however, the significance of this trend is still unclear.
Furthermore, there is the challenge of a lack of treatment for PXE. There is currently no cure for PXE; the available therapeutic options are symptom-oriented, focusing on the affected organ system. This highlights the importance of developing a treatment.
Orfenix’s commitment to developing a treatment for PXE
Together with our partners, Qualix Pharma as well as Wilko Spiering and colleagues from the University Medical Center Utrecht, Orfenix is developing a treatment for PXE. We are proud to contribute to the clinical development of etidronate disodium for the treatment of PXE. Encouragingly, clinical trial data from a study at the UECP suggests etidronate disodium may be able to slowdown the progressive calcification seen in PXE patients. Together we aim to address this unmet medical need and improve the quality of life and limit the progressive disability of PXE patients.
