Fabry disease: Emerging treatments and unmet needs
Professor Derralynn Hughes is a professor of experimental haematology with a particular interest in lysosomal storage disorders, including Fabry disease. She is also clinical director of research and innovation at the Royal Free London NHS Foundation Trust. Here, she gives her views on emerging approaches to treatment in Fabry disease and the unmet needs for patients. She particularly emphasises the need to individualise treatments
“From attending the scientific sessions at WORLDSymposium 2023, what is striking to me is the multiplicity of new approaches for treating lysosomal storage disorders that have emerged over the last few years.”
As Professor Derralynn Hughes reflects on recent years, she can see an emerging trend towards cell and gene therapies: “Going back five years, treatment mainly centred around enzyme replacement therapy, substrate reduction therapy and pharmacological chaperone therapy, but there are now different approaches being discussed related to cell and gene therapy, with new genetic approaches being explored such as gene silencing.”
She thinks the cell and gene therapy approach is a flexible one that may potentially improve the accessibility of treatment for individual very rare disorders, when compared to established therapies. “Bringing new and effective therapies to people with orphan diseases may now be much more of a reality,” she says.
“We have concentrated on replacing the enzyme that was deficient, and less so on addressing all consequences of the disease. Emerging science may mean that one day patients could potentially be offered a range of treatment options, rather than a single therapy. That might mean the different aspects of their condition could be treated.’’
Derralynn believes that new approaches could address the limitations of current treatments, but she highlights an additional challenge: “Whilst current treatments are effective, this is limited by the stage of the disease reached when people are diagnosed. The damage to organs may be less reversible when people are diagnosed and treated at a later stage. Getting an early diagnosis is therefore desirable, but there remain challenges.”
Derralynn says that newly diagnosed patients may feel relatively well and perhaps not feel the need for treatment. “The difficulty that patients have in coming to terms with their diagnosis and the need for treatment also needs to be acknowledged. We should not underestimate the impact that a rare disease diagnosis has on people.
“In the mind of a healthcare professional, it is expected that a patient diagnosed early with Fabry disease will want to begin treatment quickly, but it is still a burden for the patients to know they have the condition.”
“It is not such an easy transaction for patients as doctors may think. They know that receiving treatment may possibly impact on their quality of life.”
In the future, Derralynn would like to see newborn screening programmes for severe conditions, especially if a method of detecting people who will go on to experience significant problems is available, as well as algorithmic approaches to diagnosis.
“We may see machine learning approaches to flagging people who have yet to be diagnosed but are presenting with symptoms in various parts of a healthcare system, who then could be offered the opportunity of a genetic diagnosis,” Derralynn explains.
Machine learning approaches would have challenges, she says. People may be anxious about receiving a diagnosis and this would need to be carefully managed. There might also be concerns around privacy and data protection. “It would be important to tie machine learning up with genetic screening that fully confirms the diagnosis,” Derralynn says.
Derralynn envisages that, for some conditions, newborn screening, machine-learning approaches to diagnosis, genetic screening and a genetic approach to treatment may, one day, mean that patients get an early diagnosis followed by a one-off treatment. “But this could be some time away,” she says.
Derralynn believes it is vital to treat every person with Fabry disease as an individual and to carefully assess what their needs are, especially as the symptom burden differs between early-onset and later-onset Fabry.
“Earlier-onset Fabry patients need treatment to help protect them from damage to their heart, kidneys and brain, but which also helps them to mitigate the symptoms that impact on their quality of life.
“Later-onset patients may feel reasonably well until significant organ damage becomes evident. They may, however, need to receive treatment to prevent deterioration of organ function before they feel unwell.”
In this context, Derralynn argues that wider availability of psychological support, if desired by patients, would be beneficial. In particular, people need support with the “frustration and psychological upset” caused by the disease itself and, when their diagnosis is delayed, by the knowledge that the delay may possibly have impacted the progression of their disease.
Another area Derralynn is passionate about addressing is equitable access to diagnosis and care in rare diseases by increasing awareness of rare conditions.
“Ensuring that all individuals get equal access to an early diagnosis and then treatment is an important focus for us in this field going forward.”
This digital spotlight has been made possible with financial support from Chiesi Global Rare Diseases. With the exception of a factual accuracy check, Chiesi Global Rare Diseases has had no editorial input or control over this article’s content, which was independently created by RARE Revolution Magazine, with the interview and writing support of Rhonda Siddall of Onrush Productions. All opinions are those of the contributor. RARE Revolution Magazine and Chiesi Global Rare Diseases are not responsible for the content of any external sites linked to within this article. RARE Revolution Magazine retains all copyright.