A team of researchers recently clarified how cellular mechanisms work in the treatment of Krabbe disease. Previously, researchers believed that bone marrow transplants assisted in providing positive patient outcomes through a cellular mechanism called cross-correction. However, they have now discovered a different cellular mechanism. Find their full research study in Neuron.
Krabbe Disease
Krabbe disease is also called globoid cell leukodystrophy. This rare genetic disorder results from mutated genes that fail to produce adequate galactocerebrosidase (GALC). Normally, GALC enzymes break down lysosomes. But in patients with Krabbe Disease, fat accumulates and destroys the protective coating, called myelin, of neuronal and nervous system nerve cells.
The earlier symptoms appear, the more progressive and severe the disease is. Most patients experience symptom onset before 6 months old, with the disease growing fatal by age 2. Symptoms include vomiting, irritability, developmental delays, feeding difficulties, fever, seizures, a lack of alertness, and muscle rigidity.
However, if the disease is present in adults or adolescents, symptoms include muscle weakness, loss of dexterity or mental function, vision loss, and difficulty walking.
Currently, there are no targeted treatments for Krabbe Disease. Rather, therapies focus on symptom reduction and management, physical assistance, and nutrition. Learn more about Krabbe Disease.
Recent Research
There are no cures for Krabbe Disease. But hematopoietic stem cell transplantation (bone marrow transplant) is correlated with longer survival length and improved quality of life. Prior to this recent study, researchers believed that cross-correction, a cellular mechanism, improved patient outcomes. Basically, they believed that the bone marrow transplant helped move GALC to sick cells from the healthy, newly-implanted ones.
However, researchers wanted to better understand this process. For this study, they used Krabbe disease samples from patients, as well as animal models of the disease.
First, researchers identified which cells require GALC to function. They identified Schwann cells (which form myelin) and macrophages. Schwann cells use GALC to protect myelin and nerves from damage by preventing a buildup of psychosine. Macrophages, on the other hand, use GALC to rid the body of myelin debris.
Soon, researchers discovered that the bone marrow transplant does not cause cross-correction. Instead, it siphons GALC to already-healthy macrophages.
Moving forward, researchers hope to harness this cellular mechanism for more targeted gene therapies. They are hopeful that this will allow for the treatment of lysosomal storage disorders.
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