Chronic granulomatous disease (CGD) is a rare form of immunodeficiency. The most common form of this disease is X-linked chronic granulomatous disease (X-CGD) which is caused by a mutated CYBB gene. This mutation causes the body to be unable to properly produce gp91phox, a critical protein for the NADPH oxidase complex. Essentially, it causes an inability of white blood cells to remove fungi and bacteria from the body.
Patients diagnosed with X-GCD are-
- More often men
- Likely have a family history
- Likely to have parents who are close relatives
Symptoms include bacterial/fungal infections in the lungs, lymph nodes, liver, gastrointestinal tract, or subcutaneous tissue. Patients also face inflammation in their body as granulomas form. This inflammation can lead to an obstructed genital tract, enteritis, and other ailments.
Patients are currently treated with antibiotics or antifungal therapies; however, these are unable to stop infections from progressing.
Stem cell transplants are an option for patients, and can increase the chance of l0ng-term survival dramatically.
Unfortunately, its not any easy process. First, patients must be matched with a healthy donor which can be a difficult process in and of itself. Further, recovery from the transplant process is often a hard road. Patients can face graft-versus-host disease. There is a chance their body can reject the transplant, even when matched with a compatible donor. Additionally, there is always the chance of infection.
A solution which could eliminate many of these risks is using the patients own cells instead of the cells from a donor. This would also speed up the process, as it would eliminate the long and tedious step of finding a match.
A New Study
A new study, headed by the University of California, LA under the direction of Donald Kohn, is examining a stem cell therapy for X-GCD which utilizes the patient’s own cells. Preliminary results from this study were published in Nature Medicine. By using the patients own cells, they are able to eliminate the risk of immune rejection and increase safety overall.
This study included 4 patients in the United Kingdom and 5 in the United States. All 9 patients were between the ages of 2 and 27.
The patients own stem cells were removed, modified to correct the mutation (allowing the cells to correctly produce white blood cells), and then transplanted back into the patient.
In total, 6 of the 9 patients who received this therapy have completely recovered. They all have been able to stop their other therapies.
Sadly, 2 patients died from severe infections; however, they also had severe infections prior to entering the study.
After a 12-36 month follow-up period, the other 7 patients were found to have no new infections.
6 out of the 7 patients have been able to stop their typical treatment.
The above results are what was published in Dr. Kohn’s paper. But since publication another 4 patients have received the therapy. All of these individuals are now infection free.
So what’s next? These researchers are working with regulators in the United States and Europe to initiate larger clinical trials. Additionally, they are investigating similar therapies for other forms of CGD.
All in all, researchers are that autologous gene therapy could be a potential therapeutic option for CGD patients.
You can read more more about this investigative therapy here.