Year 4/NCE Annual

Canavan disease is a devastating disease of infants which affects their neural development and leads to mental retardation and early death. It occurs in 1 in 6,400 persons in the U.S. and there is no treatment so far. We propose to generate genetically-repaired and patient-specific stem cells (called iPSCs) from patients’ skin cells, and then coax these stem cells into specific types of corrective neural precursors using methods established in our laboratories in order to develop a therapeutic candidate for this disease.

We have demonstrated that the Canavan disease patient iPSCs hold pluripotency potential. We also genetically corrected the patient iPSCs and demonstrated that these genetically-corrected cells maintained human embryonic stem cell-like features. We coaxed these cells into specific types of neural precursors and showed that the genetically-corrected patient cells restored their cellular function.

For the reporting period, we characterized the Canavan disease mice to show that they exhibited the characteristic Canavan disease patient phenotypes. We then tested the genetically corrected cells in the Canavan disease mice for their therapeutic effect. We found that the genetically corrected cells were able to survive in the transplanted brains and express the correct lineage marker. Moreover, these cells were able to rescue the major phenotypes that are characteristic of Canavan disease patients in the transplanted mice. Our results convincingly demonstrated that the genetically corrected patient iPSC-derived cells have the potential to serve as a therapeutic tool for Canavan disease patients.

There are many families affected by this disease, and other diseases similar to it. Results from this work could have applications to this and other similar genetic diseases. Through the proposed research, maybe no parents will have to watch their child suffer and die as a result of these dreadful diseases in one day.