In 2017, CIRM funded a discovery or early stage research project for Dr. Caroline Kuo at UCLA for a hereditary immune disorder known as X-Linked Hyper IgM Syndrome. The work has gone so well that Dr. Kuo and her team are now preparing the pre-clinical work needed to launch a clinical trial.
Thanks to the success of her discovery stage project (these are intended to promote promising new technologies that could be translated to enable broad use and improve patient care), Dr. Kuo received a CIRM progression award to launch a new project for DOCK8 deficiency, a different type of Hyper IgE Syndrome. This new project will compare two gene therapy techniques as potential treatments for DOCK8 deficiency.
Hyper IgM Syndrome is a genetic disorder that occurs when there are abnormal levels of different types of antibodies (Ig) in the body. Antibodies combat infections by attaching to germs and other foreign substances, marking them for destruction. In infants with Hyper IgM Syndrome , there are normal or high levels of antibody IgM but low levels of antibodies IgG, IgA, and IgE. The low level of these antibodies make it difficult to fight off infection, resulting in frequent pneumonia, sinus infections, ear infections, and parasitic infections. Additionally, these infants have an increased risk of cancerous growths.
While X-Linked Hyper IgM Syndrome is caused by a mutation in the X gene, DOCK8 deficiency is caused by a mutation in the DOCK8 gene. More than 95% of patients with DOCK8 deficiency die by age 40.
To determine the best approach to treat DOCK8 deficiency, Dr. Kuo will compare a traditional gene therapy method with another gene therapy approach that uses CRISPR-Cas9, which work like scissors and can be directed to cut DNA at specific sites to disable, repair, or make other alterations to genes.
In a press release from UCLA, Dr. Kuo describes what inspired her to pursue this research.
“I wanted to research new treatment options for DOCK8 deficiency because I see how debilitating it can be for my patients. It’s already bad enough that my patients feel sick but then add to that visible skin infections on their hands and face that are difficult to treat, I think that’s the hardest part for a lot of the children I see. The prospect of developing a curative therapy for patients definitely brings a lot more meaning to the work.”