| ▲ Since MLD can be prevented if diagnosed early, it is argued that all newborns should be screened for MLD. (Photo = DB) |
[메디컬투데이=최재백 기자] It has been argued that all newborns should be screened for MLD to prevent metachromatic leukodystrophy (MLD).
Children with inherited MLD, a rare genetic disease, show progressive decline in thinking, motor, and sensory abilities. Pediatric patients with MLD may lose the ability to walk, swallow, speak, hear, see, respond to stimuli, and most die before the age of five.
People with the faulty MLD gene are relatively common, with about 1 in 100 people. Fortunately, MLD is inherited in a recessive way, so the disease manifests only when the faulty gene is inherited from both parents.
The faulty MLD gene causes defects in the normal enzyme Arylsulfatase A (ARSA), which breaks down a fatty substance called sulfatide in the white matter of the brain and spinal cord. Sulfatide, which is decomposed at this time, is a key component of myelin sheath that protects and insulates nerve cells. However, in MLD children with a defect in the ARSA enzyme, excessive accumulation of sulfatide in the myelin sheath inhibits nerve activity and causes inflammation.
Experts explained that when the ARSA enzyme, which is key to brain function, fails to function properly, sulfatide continues to accumulate in the brain, and by the time MLD children reach the age of 2, they lose all abilities.
There are methods to treat MLD patients by transplanting healthy bone marrow or injecting normal ARSA enzymes, but they only delay the progression of the disease rather than cure it, and the injected enzymes are large protein molecules that do not penetrate the blood-brain barrier. .
Gene therapy, which was developed under the trade name Libmeldy (atidarsagene autotemcel) in the past few years, has achieved successful results in various clinical trials by providing normal genes that make normal enzymes.
While stem cells are collected from the patient’s blood and healthy genes are inserted into the cells using an engineered virus, chemotherapy removes the abnormal stem cells remaining in the patient’s bone marrow, and finally, ‘engineered stem cells’ into which the gene has been inserted. ‘ is re-injected into the blood circulation, the stem cells migrate to the bone marrow and differentiate into normal blood cells that produce enzymes that work properly.
According to an Italian research team in January 2022, good effects were seen in most of the children treated with Livmeldi in the early stages of MLD, and Livmeldi was approved by the National Institute for Health and Care Excellence (NIHCE) in March 2022.
The cost of Livmeldi treatment was £2.87 million per patient (approximately 4.5 billion won), which was the most expensive treatment in the world at the time (currently, another gene therapy approved in the United States is the most expensive treatment).
As for the reason for the high price of Liv Meldi, experts explained that it took 20 years to develop, and that only 7 to 8 children in the UK are eligible for the indication for Liv Meldi treatment each year. In other words, a significant number of pediatric patients with MLD are only diagnosed with MLD when their older siblings reach severe symptoms, and treatment after symptoms appear is too late to prevent progression of the disease.
Accordingly, researchers, medical staff, and families of pediatric patients with MLD have requested that all newborns be screened for MLD. In the UK, blood tests currently performed on all newborns screen for nine inherited diseases, including sickle cell disease and cystic fibrosis, but not MLD.
Experts have pointed out that not screening for a fatal disease that can be prevented if diagnosed early is abandoning a minority of pediatric patients.
Currently, biochemical methods that measure sulfatide or ARSA enzyme levels in a patient’s blood can be considered as an MLD screening test, but there are limitations in that there are many false positive results. Nonetheless, experts and medical staff are emphasizing the need for MLD screening in all newborns.
Medical Today Reporter Jaebaek Choi ([email protected])
[저작권자ⓒ 메디컬투데이. 무단전재-재배포 금지]