Scientists: Monitoring is ‘key’ for presymptomatic LOPD patients
Team notes that symptoms may not start for decades after diagnosis
For people with late-onset Pompe disease (LOPD) who are diagnosed before developing symptoms, treatment can be delayed until signs of the condition become apparent, but regular monitoring is essential so that therapy is not delayed when it is needed.
That’s the argument made by a team of scientists in France in a new paper titled “Presymptomatic late-onset Pompe disease: Optimizing the timing of treatment,” which was published in the journal Revue Neurologique.Â
“We are advocating a care path based on regular patient monitoring, looking for biomarkers correlated with muscle involvement and disease activity,” the researchers concluded. “We believe that presymptomatic patients may remain asymptomatic for several decades, which makes the risk-benefit ratio of initiating treatment unfavorable. … However, the key challenge is to avoid missing the critical turning point in disease progression, when muscular or respiratory involvement becomes clinically significant.”
The team further noted that “regular assessments also provide opportunities to engage with the patient, taking their reflections and opinions into account when making treatment decisions.”
A genetic disorder, Pompe disease is marked by muscle damage due to a deficiency of the acid alpha-glucosidase enzyme, which is needed to break down complex sugar molecules in muscle cells. There are two main forms: infantile-onset Pompe disease, which develops within the first year of life, and LOPD, which doesn’t manifest until later in childhood or adulthood.
The mainstay treatment for Pompe disease is enzyme replacement therapy (ERT), which works to deliver a functional version of the deficient enzyme to the body, thus helping to slow disease progression. In children with infantile-onset Pompe, ERT has been proven to substantially improve lifespan, and it’s recommended that treatment be started as quickly as possible for these patients.
More and more LOPD patients diagnosed before symptoms start
But for LOPD, the situation isn’t so cut-and-dry. As diagnostic technology gets better and more accessible, it’s becoming increasingly common for people to be diagnosed with LOPD before they start to display any symptoms of the disease.
This has led to a debate among experts: Is it better to start treatment preemptively, or wait to start until symptoms manifest?
In this paper, the research team argued for the latter strategy. The scientists emphasized that all available ERTs carry hefty price tags, and they require patients to undergo regular infusions, which can be burdensome in terms of time and treatment accessibility. The team says it’s possible, given the available technology, to monitor patients carefully so that treatment can be started only when symptoms manifest.
Regular clinical, physiological and radiological assessments of each patient may allow for early detection of disease progression and support the [ultimate] decision to initiate treatment.
“Current guidelines provide no clear recommendations regarding the optimal timing of treatment initiation in presymptomatic patients,” the scientists wrote, stating that “regular clinical, physiological and radiological assessments of each patient may allow for early detection of disease progression and support the decision to initiate treatment.”
To illustrate their point, the researchers shared the stories of three LOPD patients whom they have helped treat. The first case was a woman who was diagnosed with LOPD after being tested because her brother had recently been diagnosed with the genetic condition. At the time, the woman had no symptoms. For the next several years, she underwent regular monitoring, including tests of walking ability and lung function, as well as MRI to look for signs of damage to her muscles.
These tests were stable for several years, but when the woman was in her early 50s, her walking got slower, lung function tests started to decline, and MRI showed signs of increasing muscle damage. She started on ERT at age 55, and the researchers report that her symptoms have been stable after more than two years since starting treatment.
The second and third cases were both similar situations, where individuals whose relatives had LOPD were also diagnosed with the disorder based on genetic testing, even though they didn’t have any symptoms. In both cases, the patients underwent regular assessments until issues started to become detectable, at which point ERT was offered.
Scientists say monitoring can delay patient treatment until necessary
The researchers proposed that this strategy could be widely applied to enable LOPD patients to benefit from treatments that help preserve their function, without burdening thems with years of infusions and high medical bills.
“The variability of severity and course of the disease should also be taken into account in the treatment decision, as some patients may present mild muscle weakness for years, allowing to delay ERT introduction while carefully monitoring disease progression with standardized exams,” the team concluded.
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