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Turning the tide for rare disease

Libmeldy gene therapy offers a lifeline to children with leukodystrophy and gives hope to the rare disease community

by Geoff Case

Libmeldy is a lentiviral stem cell gene therapy for metachromatic leukodystrophy (MLD). It is the first treatment of its kind to be approved by Nice for reimbursement by the NHS in England, following a successful clinical trial. 

Vivienne Clark of the MLD Support Association UK met with our digital editor, Geoff Case, to explain the nature and progression of MLD, the terrible impact on families and the pressing need for an early diagnosis now that treatment is available. She describes Libmeldy as a step change that heralds a brighter future, not just for the MLD community but also for the wider rare disease community.

Metachromatic leukodystrophy (MLD)

To fully appreciate the magnitude of the breakthrough offered by this new gene therapy, it is necessary to understand what MLD is and its deadly progression in children. 

Vivienne explains that MLD can broadly be categorised as late-infantile, juvenile and adult. 

The late-infantile type of MLD is the most common form of the disease. It starts before 30 months and progresses rapidly. Most children soon lose their ability to walk and talk, and they usually die between the ages of five and eight.

Individuals affected as juveniles make it to school, and then evidence begins of cognitive problems: “Often they start appearing disruptive in class and show a lack of attention.” As well as cognitive problems, their gait and balance will be affected. These issues, Vivienne says, are often first noticed by school nurses or teachers. 

Following these initial symptoms, juvenile MLD tragically follows a much slower but very similar trajectory to the late-infantile form, ending in the child becoming blind, immobile, unresponsive and unable to speak.

Adult-onset MLD is a “completely different story”. Often this presents as schizophrenia, so patients are referred to psychiatrists, and most of them don’t get diagnosed properly. Unfortunately, adult-onset MLD also ends in early death.

Vivienne’s own son has adult-onset MLD. He had a bone marrow transplant in 1996 and is now nearing his fiftieth birthday. Although he is cognitively impaired and lives in a care home, “he walks, talks, runs, jumps, goes to the pub and has a great quality of life”. It is thought, Vivienne says, that adult-onset MLD is “under-diagnosed”.

Libmeldy has been recommended by Nice:

  • for children who have late infantile or early juvenile types, with no clinical signs or symptoms
  • for children who have the early juvenile type, with early clinical signs or symptoms, and who can still walk independently and have no cognitive decline.

MLD’s devastating impact on families

Vivienne explains the absolutely devastating impact of MLD on families: “After a diagnosis, one of the parents has to stop work and sometimes both. The pressure on them is 24/7. They do get some help in the later stages, but never what they need. There’s lack of sleep, lack of support, isolation, financial problems, marital problems.” It is not just the parents who are affected either: “the siblings who are healthy are inevitably shunted to one side because you’ve got this terribly sick child that needs to be cared for”. 

Vivienne praises the key role played by the MLD community in helping Nice understand the awful suffering involved in MLD. Families were asked to participate in a very detailed questionnaire and “the response was unbelievable. Some respondents went on to do very in-depth interviews as well. So, even though they had no chance of benefiting from Libmeldy, they were happy that they could stop someone else from suffering.

“Without the survey, I don’t think Nice would have realised how terrible the disease is and the impact on the family. It isn’t just on the child and the parents. It’s the entire extended family.”

The pressing need for early diagnosis and greater awareness

Now that Libmeldy has been recommended for treatment, the pressing need for early diagnosis is clear, as only if the disease is diagnosed early enough can Libmeldy be administered. 

Vivienne is pleased that trials for bloodspot of MLD are taking place in different countries. While the test is not an easy one, because of the fragility of the enzyme concerned, she is sure that there is much potential there. If newborn screening in the UK could be expanded to include a wider range of rare diseases—as is the case in some other countries—the benefits would be considerable.

“Currently, children with later stage MLD may go to hospital once a week for many weeks, they may also need to be admitted to a paediatric intensive care unit; they have 24/7 nursing care; they even have their houses altered. It’s cheaper in the long run to pick conditions up and treat them.” 

Vivienne points out how, if people with rare diseases could be identified earlier, through newborn screening, many would be able to go to work and pay into society—of course, this would be true for their parents too.

Clearly, with leukodystrophy, the oft-seen primary care strategy of watchful waiting cannot be an option. Delaying the possibility of treatment is deadly. Now that a treatment has been found, the message to healthcare professionals is “don’t watch and wait: do something”—a message that the MLD Support Association UK will be sending out loud and clear.

It is vital, Vivienne says, that GPs know about MLD so that individuals can be referred early enough to a specialist who can deal with the disease. “There are now centres that they can go to; you’ve got Great Ormond Street, Birmingham and Manchester. If children are sent to the centres, they will be tested properly, but it’s getting them there. That means getting the awareness at that lower level.”

As well as its work to raise awareness, the MLD Support Association UK will be continuing its invaluable work supporting families: “We’re there when they phone up after they get their diagnosis—inevitably they’re devastated. So, we have someone who can speak to them and visit them, if necessary, to ensure they’re getting the right help and point them in the right direction.” There are also two Facebook groups, a public and a closed one, to connect the community. This enables the parents to interact and support each other. It also means the association can inform parents of events, such as the association’s upcoming family fun day. 

A brighter future for the wider rare disease community

Vivienne is hugely excited about Libmeldy and the brighter future that it offers for the MLD community. Having had such a long involvement with MLD, she has been able to see the progression in the field “from the first bone marrow transplants in the eighties, improvements in bone marrow transplants, realising that the stem cells would be the thing, and going towards gene therapy to get the vectoring.” 

With Libmeldy representing such a step change for MLD, could its advent also herald a bright new dawn for the wider rare disease community? For Vivienne, the answer is a resounding “yes”.

“For the first time, a rare disease has a treatment that can potentially cure through replacing a missing enzyme. But, if this can happen for MLD, one of the ‘more common’ rare diseases, it could also happen for no end of rare diseases.”

Libmeldy is a lentiviral stem cell gene therapy for metachromatic leukodystrophy (MLD). It is the first treatment of its kind to be approved by Nice

www.mldsupportuk.org.uk


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