Genetic diagnostic technology a game changer for rare diseases, but ethics concerns linger

Genetic diagnostic technology advances for rare diseases offer hope, but gene-tech comes wrapped in complex ethical concerns. Currently, rare disease patients take an average of five years to get a diagnosis, with many misdiagnoses. So will Europe accelerate modern diagnostics, or will ethical concerns stifle innovation?

Around 30 million Europeans are living with a rare disease, and less than 5% of rare conditions are effectively treated. For rare diseases that do not present symptoms early on, newborn screening programs are important, especially when early intervention may prevent symptoms or disease progression, as EURORDIS-Rare Disease Europe points out.

“The best way to reduce the whole diagnosis odyssey remains access to new-born screening because it can shorten the time it takes to see a doctor, but also to have access to a diagnosis once you have had the first consultation” said Jessie Dubief, Social Research Director for EURORDIS, during the European Conference on Rare Diseases and Orphan Products (ECRD) on 15 May, in Brussels.

More than 70% of rare diseases have genetic origins. As scientific knowledge advances and genome sequencing technology improves, the question that has become even more significant is whether newborn screening programs should expand and include new sequencing techniques.

“It could change children’s lives. You can diagnose a rare disease at a time that allows you to treat them effectively because you ‘caught it’ early on,” Theoklis Zaoutis, Professor of paediatrics and former president of EODY, the Greek public health agency, told Euractiv.

New-born screening acceptance

A recent comprehensive survey by EURORDIS showed broad support from the rare disease community for newborn screening as an essential early healthcare intervention.

Of the participants, 73% either strongly agreed or agreed, that they would have liked to have been diagnosed at birth or for a family member living with a rare disease to have been diagnosed at birth.

Also, when looking at surveys at the general population level this idea was even more widely accepted, remarked Dubief while presenting the study’s results at ECRD.

Additionally, 90% of respondents think that any rare disease should be screened at birth if it would lead to a quicker diagnosis, a diagnosis that would benefit both the patient and their family, if it would allow better recognition of a person’s disabilities, and promote rare disease follow-up and harm avoidance, through prevention.

“It is crucial that European policymakers, at both the national and international levels, act now to diminish disparities in new-born screening programmes across different countries, enhancing the quality of life for all children, irrespective of their birthplace,” said Virginie Bros-Facer, the new CEO of EURORDIS.

“It is high time that advancements in public policy catch up with the scientific and technological advancements that we have seen in diagnostics,” she added.

As Yann Le Cam, Founder and Past Chief Executive Officer of EURORDIS, commented to Euractiv, what should be done is to “agree at the European level on what level of evidence we need to show the benefit of having a new-born screening program and to have also studied on the health economy of that.”

Then, he said, “Based on this evidence, which can be collected a few years before the approval of medicines, make a decision and link access to the medicines with newborn screening.”

Genome sequencing possibilities

In the last decades, genomic sequencing technologies have gradually become important in understanding disease, improving, and shortening the diagnostic path, and identifying targets or mechanisms that medicines could affect.

As more targeted medicines are developed, it is also crucial to identify the patient who would benefit the most at the right time.

To further understand the ability of sequencing babies’ genomes to discover rare genetic conditions earlier, Genomics England is running an NHS-embedded research study.

“It aims to look at the DNA of over 100,000 babies and gather evidence to consider whether whole genome sequencing could be rolled out as part of a future newborn screening programme,” as it is described. The initial list holds over 200 rare conditions that will be looked for.

On the other side of Europe, another study involving ‘New-born Sequencing’ is being rolled out in Greece.

First Steps Initiative

The First Steps initiative is a national program that uses whole genome sequencing (WGS) as a screening tool for newborns to identify genetic conditions before symptoms present.

As Petros Tsipouras, CEO of PlumCare and scientific director of First Steps, explained during ECRD, the first part of the study plans to enrol at least 1,000 families through three university hospitals in Greece by the end of this year.

“We have a mandate from the Greek government to screen 100,000 babies in the next three years,” he explained, adding that phase II will aim to include 20,000 babies starting in 2025, while phase III will aim to screen all babies born in Greece.

It screens for 510 diseases for which there is an intervention. It is an informed consent-based clinical study. It is under the auspices of EODY.

“WGS technology provides a tremendous opportunity for us to expand our newborn screening programs. As you know, there are many rare diseases that we do not necessarily screen for presently, and it won’t be cost-effective at this time to screen for them,” Professor Zaoutis told Euractiv.

“Whole genome screening provides the kind of technology that allows us to identify rare diseases and act on them because there are some rare conditions that, if you catch them early on, you could change the outcome of the child’s life,” he underlined.

As he explained, WGS’s basic advantage is that you can screen for hundreds of rare diseases with one sample.

“Rapid WGS within 18 to 24 hours can be lifesaving. 37% of babies admitted to an ICU have an underlying genetic problem, for which having rapid WGS and introducing an intervention is lifesaving,” Tsipouras highlighted.

Ethical aspects

The advancement and wider use of genetic testing isn’t the only focus of discussion, though. With the progression of screening technology, ethical concerns have risen.

As has been reported, ethical aspects concern, among others, the procedure of genetic testing for rare diseases (such as obtaining informed consent or interpreting the test results), the delivery of results, the decisions that follow, and the possibility of facing stigma and discrimination from the outcome.

This point was also made during the discussion in ECRD.

“If we want to bring real equity across a country’s population, new-born sequencing can do that, as you screen all babies born in the country, so there is no discrimination,” Tsipouras commented.

However, he added: “Feasibility, clinical utility and societal acceptance need to be in place before a public health measure is established.”

“A public debate is needed on [the issue of new-born sequencing] because it is the future. We must drive [the discussion] on this pathway we are moving on. It should be an informed decision; we have to raise awareness on all the challenges and advantages,” Simona Bellagambi, from the Italian rare disease federation UNIAMO, said during the discussion in ECRD.

“Data confidentiality; a person’s genome should be accessed only by them and not be publicly available. If it is, identifiers should be omitted, and data should be anonymised,” Zaoutis said.

“We must put in place all the necessary safeguards around data and privacy protection,” he concluded.

“We need to go stepwise, but that’s certainly not a reason not to scale up,” Le Cam had commented on the issue, adding that “it’s not a good route neither to immediately move to large-scale genome sequencing without further study and evaluation of that new knowledge.”

“We need time to generate more knowledge because we see some of the benefits, but we also see some of the risks,” he concluded.

[By Vasiliki Angouridi, Edited by Brian Maguire | Euractiv’s Advocacy Lab]

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