The active substance in Libmeldy is stem cells, (CD34+ cells), derived from the patient’s own bone marrow or blood, that have been modified to contain a copy of the gene to make ARSA and can divide to produce other sorts of blood cells. Atidarsagene autotemcel
A gene therapy called atidarsagene autotemcel was approved for medical use in the European Union in December 2020 and is sold under the trade name Libmeldy. The indication is for use in children with the late infantile or early juvenile forms of MLD who have been identified as carriers of the defective gene but have not yet developed symptoms. It is also indicated in children who have been diagnosed with the early juvenile form who have started developing symptoms but still have the ability to walk independently and before the onset of cognitive decline.In the United States, an Investigational New Drug application for atidarsagene autotemcel was accepted by the Food and Drug Administration in late 2020. Research directions
Several therapy options are currently being investigated using clinical trials primarily in late infantile patients. These therapies include gene therapy, enzyme replacement therapy (ERT), substrate reduction therapy (SRT), and potentially enzyme enhancement therapy (EET). In addition to the clinical trials, there are several other pre-clinical gene therapy research projects underway. Epidemiology
The incidence of metachromatic leukodystrophy is estimated to occur in 1 in 40,000 to 1 in 160,000 individuals worldwide.
The inheritance probabilities per birth are as follows:
If both parents are carriers:
25% (1 in 4) children will have the disease
50% (2 in 4) children will be carriers, but unaffected
25% (1 in 4) children will be free of MLD – unaffected child that is not a carrier
If one parent is affected and one is free of MLD:
0% (0) children will have the disorder – only one parent is affected, other parent always gives normal gene
100% (4 in 4) children will be carriers (but unaffected)
If one parent is a carrier and the other is free of MLD:
50% (2 in 4) children will be carriers (but unaffected)
50% (2 in 4) children will be free of MLD – unaffected child that is not a carrierIn addition to these frequencies there is a pseudo-deficiency that affects 7–15% of the population. People with the pseudo deficiency do not have any MLD problems unless they also have affected status. With the current diagnostic tests, Pseudo-deficiency reports as low enzyme levels but sulfatide is processed normally so MLD symptoms do not exist. This phenomenon wreaks havoc with traditional approaches to Newborn Screening so new screening methods are being developed. Diagnosis
Clinical examination and MRI are often the first steps in an MLD diagnosis. MRI can be indicative of MLD but is not adequate as a confirming test. An ARSA-A enzyme level blood test with a confirming urinary sulfatide test is the best biochemical test for MLD. The confirming urinary sulfatide is important to distinguish between MLD and pseudo-MLD blood results.