Myotonic Dystrophy Stem Cells

Published on Thu, 04/23/2015

Modifying the DNA of DM Stem Cells to Treat Symptoms

Researchers at the University of Florida, led by Dr. Tetsuo Ashizawa, recently published a study in which they developed a strategy for DM1 stem cell therapy involving gene modification. This proof-of-concept study demonstrated that the genetic approach designed by the Ashizawa lab could be effective in reversing cellular defects that cause DM symptoms. Someday successful gene modification could be used to enable personalized stem cell therapy, in which cells are obtained from a person with DM1, treated to address the gene mutation, and transplanted back into the patient with the hope of restoring normal tissue function and treating symptoms.

Dr. Ashizawa's lab used cells obtained from skin biopsies of people with DM1. The cells were converted to stem cells called induced pluripotent stem cells (iPSCs) that can produce cells for every tissue in the body. The stem cells were then converted to develop brain cells. Following this conversion, the DMPK gene in the brain cells was targeted to reverse negative effects of the DM1 mutation that causes disease symptoms. This strategy proved to be effective, as the lab successfully genetically modified the brain cells, and restored normal cell function.

Despite the positive study results, limitations and challenges exist that must be addressed before this approach can be used to treat people with DM1. First, additional research must demonstrate that this genetic approach is safe as a treatment. Genetic modification of cells can result in unexpected side effects, such as unwanted mutations elsewhere in the gene. Secondly, the modification to the DMPK gene may have negative effects on normal gene function, and we need to explore this possibility. In addition, we need to improve the transfer of modified stem cells into brain, muscle, and heart tissue in order to get the best possible impact on disease symptoms.

While Dr. Ashizawa's team and others are conducting studies to address these challenges, this study is an exciting first step in efforts to build a stem cell therapy for DM1 and move gene therapy for DM1 to the clinic.

Read the abstract of this study.