This past week, CIRM-funded studies have been widely discussed, highlighting the importance of the work we support and the different disease areas we impact. This includes important research related to rare disease, Type 1 Diabetes (T1D), and heart function. Below is a summary of the promising CIRM-funded studies released this past week for each area.

Rare Disease

Pelizaeus-Merzbacher disease (PMD) is a rare genetic condition affecting boys. It can be fatal before 10 years of age and symptoms of the disease include weakness and breathing difficulties. PMD is caused by disrupted myelin formation, the insulation around nerve fibers that allows electrical signals in the brain to travel quickly. Without proper signaling, the brain has difficulty communicating with the rest of the body. Although we know what causes PMD, it remains unclear why myelin formation is disrupted in the first place.

However, in a CIRM-funded study, Dr. David Rowitch and a team of researchers at UCSF, Stanford, and the University of Cambridge have been developing potential stem cell therapies to reverse or prevent myelin loss in PMD patients.

Two new studies, in which Dr. Rowitch is the primary author, published in Cell Stem Cell and Stem Cell Reports, respectively, report promising progress in using patient-derived stem cells to identify new PMD drugs and in efforts to treat the disease by directly transplanting neural stem cells into patients’ brains. 

In a UCSF press release, Dr. Rowitch talks about the implications of his findings, stating that,

“Together these studies advance the field of stem cell medicine by showing how a drug therapy could benefit myelination and also that neural stem cell transplantation directly into the brains of boys with PMD is safe.”

Type 1 Diabetes

Viacyte, a company developing a treatment for Type 1 Diabetes (T1D), announced in a press release that it presented preliminary data from a CIRM-funded clinical trial showing promising results. T1D is an autoimmune disease in which the body’s immune system destroys the cells in the pancreas that make insulin, a hormone that helps the body break down sugar in the blood. CIRM has funded ViaCyte since its earliest days, investing more than $72 million in the company.

The study uses pancreatic precursor cells derived from stem cells and implants them into patients using an encapsulation device. Preliminary data showed that the implanted cells, when effectively engrafted, can produce circulating C-peptide, a biomarker for insulin, in patients with T1D. The procedure needs further optimization.

“This is encouraging news,” said Dr. Maria Millan, President and CEO of CIRM. “We are very aware of the major biologic and technical challenges of an implantable cell therapy for Type 1 Diabetes, so this early biologic signal in patients is an important step for the Viacyte program.”

Heart Function

Although various genome studies have uncovered over 500 genetic variants linked to heart function, such as irregular heart rhythms and heart rate, it remains unclear how they influence heart function.

In a CIRM-funded study, Dr. Kelly Frazer and her team at UCSD further examined this link by deriving heart cells from induced pluripotent stem cells. The team derived these stem cells from skin samples from seven family members. After extensive genome-wide analysis, the team found that many of these genetic variations influence heart function because they affect binding to a protein called NKX2-5.

In a press release by UCSD, Dr. Frazer elaborated on the important role this protein plays by stating that,

“NKX2-5 binds to many different places in the genome near heart genes, so it makes sense that variation in the factor itself or the DNA to which it binds would affect that function. As a result, we are finding that multiple heart-related traits can share a common mechanism — in this case, differential binding of NKX2-5 due to DNA variants.”

The full results of this study were published in Nature Genetics.