Gene Therapy Offers A New Lease On Life For Children With Metachromatic Leukodystrophy (MLD)
Metachromatic leukodystrophy or MLD is a rare genetic condition that is characterized by an accumulation of fatty substances or lipids in cells, especially in the brain, spinal cord, and peripheral nerves. This happens because of an abnormality in the gene for MLD - the ARSA and PSAP genes. As a result of this abnormality, they produce a defective version of the enzyme needed to break down lipids. As a result, these lipids that are called sulfatides begin to accumulate in the myelin sheath, which is a fatty sheath that protects nerve cells. While sulfatides play a vital role under normal circumstances, this kind of a buildup causes disruption of nerve activity and inflammation. This in turn leads to progressive deterioration of brain and nervous system function.
How Metachromatic Leukodystrophy Affects Children
Children with MLD suffer a progressive decline in intellectual functions and the loss of motor skills. This affects learning and thinking as well as the ability to walk or simply respond to stimuli. They also suffer from other symptoms such as loss of sensation in the extremities, seizures, paralysis, loss of speech, vision loss, and hearing loss. As the condition progresses, children eventually become unresponsive, even losing awareness of surroundings.
So far, the outlook for children with MLD has been bleak, with most children who develop the condition during infancy succumbing to the illness by the age of 5 years. The fact that MLD is a rare disease offers little comfort to grieving parents and families.
Limitations Of Conventional Treatments
Conventional treatments for MLD have been severely limited. One of these treatments requires bone marrow transplants from healthy donors, but this depends on the availability of suitable donors and it only delays disease progression.
Similarly, there has been interest in intravenous administration of the working enzyme to patients to slow disease progression - enzyme replacement therapy. Unfortunately, this approach is regarded as ineffective as the enzyme is a large protein molecule, which means that it cannot cross the blood-brain barrier to stop lipid accumulation.
How Gene Therapy Transforms MLD Outcomes
In recent years, advances in gene therapy have brought new hope to children with MLD. There have already been successful clinical trials for new gene therapy treatment called atidarsagene autotemcel. So, what does this therapy involve?
Stem cells, which originate in bone marrow, can develop into a variety of blood cells and are taken from a patient. These stem cells are modified in a lab, with healthy copies of the required gene inserted into their DNA. Children with MLD undergo simultaneous treatment to destroy any remaining unmodified stem cells in their bone marrow.
Once the unmodified stem cells have been destroyed and the modified stem cells created, these modified stem cells are introduced into the bloodstream so that they can migrate to the bone marrow and begin production of blood cells that now have the ability to create the enzyme.
In the last year, researchers found that this type of gene therapy for MLD is effective in most children with early onset MLD. In such cases, the treatment was shown to preserve cognitive function and motor development, protecting against demyelination and brain atrophy.
Considerations For Parents
Although gene therapy can give children with MLD a new lease on life, it is only effective for children with early onset MLD. Tragically, MLD is often diagnosed only when it has progressed to cause severe illness. At this point, when symptoms have surfaced, disease progression cannot be controlled with any treatment. To reap the benefits of gene therapy for MLD in children we need to take preventive action, screening newborn babies for the condition as this gene therapy is most effective when treatment begins before symptom onset. Gene therapy can also be beneficial in managing other conditions. Learn more about gene therapy for ocular diseases and gene therapy for hemophilia here.
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