Treatment for Krabbe Disease

As of now, there is no cure for Krabbe Disease (Yagasaki et al., 2011). The currently used therapy for early infantile, late infantile, and juvenile forms of Krabbe Disease is hematopoietic stem cell transplantation in order to deliver stem cells to the patient that have wild type copies of the GALC gene; this attenuates symptoms temporarily but it not a long-term solution  (Gelinas et al., 2012). Adult forms of Krabbe Disease often progress very slowly and are treated primarily by symptom management (Duffner et al., 2012). Bone marrow transplant has been the predominant method of hematopoietic stem cell transplantation (Yeager et al., 1984). However, this is a very invasive procedure for such a young child; recently, physicians have begun to use umbilical cord blood stem cell transplant for pediatric patients due to the increased concentrated of hematopoietic stem cells in umbilical cord blood and the smaller volume of blood that needs to be injected into the patient (Yagasaki et al., 2011). Transplants in general still pose significant mortality rates for children—about 15%– due to the immunosuppressive myeloablative treatment administered prior to the procedure in order to eliminate the patient’s hematopoietic stem cells (Duffner et al., 2012).

Current studies are underway to improve the efficacy of hematopoietic stem cell transplant and resulting gene therapy by exploiting hematopoietic stem cell miRNAs to appropriately time the induction of β-galactocerebrosidase expression (Gentner et al., 2012).  Additionally, the use of hematopoietic stem cell transplant as a treatment method for adolescent/adult onset is being explored more thoroughly to see if it can be effective (Sharp et al., 2013). Neural stem cell therapy (Taylor et al., 2006) and stromal cells injection therapy (Wicks et al., 2011) are currently being tested in mice. Neural stem cell therapy especially seems to be particularly effective for mice with demyelination disorders, although Krabbe Disease Twitcher mice have yet to be tested (Uchida et al., 2012).

In addition to stem cell transplant, recent studies are also beginning to look to small molecule studies and enzyme replacement therapy.  In 2012, gene therapy accomplished through adenovirus infection of Twitcher mice showed elevated galactocerebrosidase in the brain and CNS. Normal disease pathology in the mice was significantly reduced—the mice maintained a healthy weight, lived up to 8 months, and hardly twitched (Rafi et al., 2012). Last year, Ribbens et al. designed an assay by which small molecule enhancers of galactocerebrosidase may be screened– this could be a promising beginning to small molecule studies in Krabbe Disease.

 

Figure 1. This is a diagram outlining the process of hematopoietic stem cell transplant. Allogenic transplant means that the stem cells are coming from a donor versus the patient. Image Source
Figure 1. This is a diagram outlining the process of hematopoietic stem cell transplant. Allogenic transplant means that the stem cells are coming from a donor versus the patient. Image Source

 

Figure 2. Umbilical cord stem cell transplant seems to be a safer method for children with Krabbe Disease. Image Source
Figure 2. Umbilical cord stem cell transplant seems to be a safer method for children with Krabbe Disease. Image Source

 

Click on the following links to learn more about Krabbe Disease!

History and Metabolic Context of Krabbe Disease

Molecular Basis of Krabbe Disease

Proposals for Future Research