eddi Shaw has become the first patient in the UK to receive Libmeldy, a medication that treats the genetic flaw at the root of metachromatic leukodystrophy (MLD).
The list price of gene therapy, which replaces a damaged gene within the body’s cells, is £2.8 million.
Shaw no longer exhibits symptoms of MLD, a condition that is described as incurable, and progressively damages the nervous system and organs.
Nala and her three-year-old sister Nala were both diagnosed with MLD in April last year.
Clinical advice that treatment should begin before the condition goes too far and causes irreversible damage prevented Nala from receiving it.
What is MLD?
According to Great Ormond Street Hospital for Children MLD and Libmeldy, MLD is a rare inherited neurometabolic disease that causes rapid and progressive demyelination and neurodegeneration, leading to severe neurological disability and death.
MLD is sometimes known by its medical description: sulphatide lipidosis or sulphatidosis. The late-infantile form may also be called Greenfield’s disease.
It is estimated that the incidence in the UK is approximately one in 40,000.
One of a group of leukodystrophies (rare genetic disorders that affect the central nervous system) known as MLD is brought on by an abnormal build-up of substances (metachromatic material known as sulphatides) in the nerve cells, particularly in the white matter of the brain, which replace myelin, the insulating material required for normal transmission of messages between nerves.
These substances are normally broken down and removed from the body by an enzyme (arylsulphatase A) but, in MLD, the gene responsible for producing the enzyme is faulty so the normal process cannot occur.
Because the brain serves as the body’s command centre, obstructions in the messages travelling to other body parts will hinder those parts from functioning effectively, even though the parts themselves appear to be in good health.
MLD is a progressive disease. Infantile MLD represents around half of all MLD cases and most infants with this form die by age five. Death occurs 10 to 20 years following juvenile onset. While people affected by the adult form typically die within six to 14 years following initial symptoms.
What are the symptoms of MLD?
According to Leukodystrophy Resource Research Org Inc, symptoms include:
- Walking difficulties
- Hypotonia: low muscle tone
- Muscle spasms and cramps
- Strabismus : cross-eyed
- Spasticity: increased reflexes
- Nystagmus: involuntary eye movement
- Loss of sight
- Swallowing problems
- Decreased speech
- Seizures
- Ataxia: loss of the ability to co-ordinate muscular movement
- Paralysis
- Eventual absence of voluntary functions
How is MLD diagnosed?
An MRI brain scan may suggest the diagnosis which can be confirmed with a blood test to check for the absence of arylsulphatase A and a urine test to show the sulphatides.
MLD is an autosomal recessive disorder, which means that both parents have to be carriers of the disease. Prenatal testing is usually possible by chorionic villus sampling early in pregnancy.
Who is susceptible to MLD?
MLD is rare and has a worldwide incidence of one in 160,000 births. However, Habbanite Jews (one in 75), certain Arab groups in Israel (one in 8,000), and populations from the western portion of the Navajo Nation (one in 2,500) are more susceptible than the general population, according to the Leukodystrophy Resource Research Org Inc website.
What are the treatments for MLD?
Libmeldy is the first treatment made for MLD, it is an autologous haematopoietic stem cell (HSC) gene-therapy product made specifically for each patient using the patient’s own blood stem cells. It works by replacing the faulty gene that causes the disorder.
Other than Libmeldy, every attempt is made to address the symptoms as they arise. Drugs can be administered to treat infections, ease muscle spasms, and attempt to control seizures (should they occur). If necessary, sedatives and painkillers can be administered, and feeding assistance is also available. Parents also receive guidance on positioning, seating, and limb exercise to preserve comfort from physiotherapists and others.
The one-off treatment has a list price of £2.8 million but can be offered on the NHS after the health service negotiated a confidential discount.
It is being delivered in the UK within Royal Manchester Children’s Hospital – in collaboration with Manchester’s Centre for Genomic Medicine at Saint Mary’s Hospital – both part of Manchester University NHS Foundation Trust (MFT).
The centre in Manchester is one of just five European sites administering the treatment, and the only site in the UK, according to the NHS.
For further information and support in the UK, visit MLD Support Association UK.
