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.
For the reporting period, we have obtained primary dermal fibroblasts from clinically affected Canavan disease patients and have derived Canavan disease patient iPSCs. We have demonstrated that these iPSCs exhibited typical human embryonic stem cell (ESC) like morphology, expressed human ESC cell surface markers and hold pluripotency potential. We are also optimizing methods to coax these cells into specific types of neural precursors. Either the patient iPSCs or their neural precursor derivatives will be genetically corrected in the following years to develop 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.