Researchers at Washington University School of Medicine in St Louis, Missouri, used CRISPR/Cas9 to correct a genetic defect in human stem cells and then converted them into cells capable of producing insulin. When these edited insulin-producing cells were implanted into diabetic mice, they were able to effectively control blood sugar levels for six months.
'We're excited about the fact that we were able to combine these two technologies - growing beta cells from induced pluripotent stem cells and using CRISPR to correct genetic defects,' said corresponding author Dr Jeffrey Millman. 'This is the first time CRISPR has been used to fix a patient's diabetes-causing genetic defect and successfully reverse diabetes.'
The human cells used were from a patient with a rare genetic type of diabetes called Wolfram syndrome, which develops during childhood and typically requires affected patients to inject insulin multiple times each day.
'For this study, we used cells from a patient with Wolfram syndrome because, conceptually, we knew it would be easier to correct a defect caused by a single gene. But we see this as a stepping-stone toward applying gene therapy to a broader population of patients with diabetes,' said Dr Millman.
The same team previously developed a new technique to more efficiently convert human stem cells into insulin-producing cells, allowing them to 'functionally cure' diabetes in mice for the first time (see BioNews 1037). In the current study, they went one step further, adding the genome editing step to make cells from a diabetic person produce insulin.
'We basically were able to use these cells to cure the problem, making normal beta cells by correcting this mutation,' said Dr Fumihiko Urano, who co-led the study. 'In fact, we found that corrected beta cells were indistinguishable from beta cells made from the stem cells of healthy people without diabetes,' added Dr Millman.
'It's also possible that by correcting the genetic defects in these cells, we may correct other problems Wolfram syndrome patients experience, such as visual impairment and neurodegeneration' said Dr Urano.
The study was published in the journal Science Translational Medicine.