(1) Hepatocyte Transplantation and (2) Gene Therapy:
Right now the best treatment for Wilson’s Disease is a liver transplant, which would provide patients with a healthy liver that had a functioning ATP7B protein. Liver transplant has been shown to improve Wilson’s Disease symptoms over 1-5 years. However, Wilson’s Disease patients who have failed other treatment options for Wilson’s Disease suffer while waiting on lengthy transplant lists. It has also been difficult for the medical community to come to a consensus about when it is necessary for Wilson’s Disease patients to have transplants.
Recent research has shown that hepatocyte transplantation and gene therapy are up and coming treatments that have developed in tandem and solve many of these problems. Hepatocyte therapy involves obtaining hepatocytes from a donor liver. (Gupta 2014) (Rosencrantz et.al. 2011) Gene therapy technology is then used to culture these hepatocytes in the lab with the genes that the recipient patient is missing (in the case of Wilson’s Disease this would be the Wilson’s Disease gene). (Gupta 2014) The cultured hepatocytes are then transplanted into a patient’s diseased liver and bile duct. (Gupta 2014) The healthy hepatocytes proliferate and help to regenerate the diseased liver. (Gupta 2014) In the case of Wilson’s Disease, the transplanted hepatocytes contain a functional ATP7B protein that can work to effectively transport copper in the liver and the patient’s symptoms would subside. An image depicting the flow of this treatment can be seen in Figure 1 below. Hepatocyte transplantation is a more sustainable and feasible option for Wilson’s Disease patients than whole liver transplant. Since the hepatocytes are being transplanted onto the patient’s existing liver, the transplant is less metabolically stressful on the patient because their liver architecture is maintained. (Rosencrantz et.al. 2011) Additionally, because the patient is not undergoing a full liver transplant, there is a decreased risk of rejection. Also, one donor liver has the potential to provide hepatocytes for several hepatocyte transplants. Gene therapy may also be used effectively in the future in the host to prevent transplant rejection, a big risk with whole liver transplant. This treatment provides the potential for a cure for Wilson’s Disease.
However, future research is needed in this area before this can become a mainstream treatment for Wilson’s Disease, or any liver disease for that matter. Right now there are a shortage of quality liver donors to provide hepatocytes for the transplants. Additionally, we have not yet developed dependable methods for cryopreservation of hepatocytes, so many of the isolated hepatocytes become too damaged to use before they can be transplanted. Gene therapy and hepatocyte transplantation also need to undergo trials in humans. As of now, these methods have been tested mainly in animal models. Developing these therapies would provide sustainable treatment for not only Wilson’s Disease, but a variety of other liver diseases, both inherited and acquired.
(3) Susceptibility Weight Imaging (SWI) as a New Method of Detection:
Currently, Magnetic Resonance Imaging (MRI) is used to image the brains of Wilson’s Disease patients to examine the extent of copper deposition in their brain. However, more sensitive imaging is needed to detect copper metabolism in the brain more effectively. A new study has also proposed using new SWI, susceptibility weighted imaging (sometimes referred to as BOLD venographic imaging), technology that is more sensitive than MRI at detecting mineral deposits in the brain. (Xiang-Xue et. al. 2014) SWI uses a GRE (gradient recalled echo) pulse sequence to acquire images which allows SWI to pick up on specific differences in tissues. (Xiang-Xue et. al. 2014) Because of this, SWI is effective at looking at venous blood and metal storage. (Xiang-Xue et. al. 2014) SWI is currently being used mainly for detecting traumatic brain injury because of its sensitivity dependence on blood oxygen levels. However, new research has also shown that SWI is capable of detecting abnormal iron and copper metabolism in the brain. (Xiang-Xue et. al. 2014) Another study on the use of SWI and Wilson’s Disease has used SWI to look at copper deposition specifically in the deep grey nuclei in the brains of Wilson’s Disease patients. (Bai et. al. 2014) They have found that there is an increased abnormal phase value in the brains of Wilson’s Disease patients and propose that this shift could be used as a biomarker for detecting Wilson’s Disease in patients. (Bai et. al. 2014) However, more research is required before SWI can be put into widespread use for detecting Wilson’s Disease. SWI could serve as an important diagnostic tool for Wilson’s Disease in the future. An SWI image of the copper deposition in a Wilson’s Disease brain can be seen below in Figure 2.
Many advances have been made in the identification and treatment of Wilson’s Disease since Kinnier Wilson first discovered it in 1912. More effective treatments such as zinc therapy and more effective diagnostics such as specific blood and urine tests have been developed. However, there is still no widely available, life long cure for Wilson’s Disease and therefore many people continue to suffer. The avenues for research outlined above as well as potentially looking into new treatments such as enzyme replacement therapy and new nanoparticles that could be injected into liver cells and selectively detoxify copper.(Kandanapitiye et.al. 2015) Research should also look into new diagnostic tests that can detect Wilson’s Disease before significant copper deposition has occurred would be viable avenues for future research. Hopefully in future years research will continue to search for better diagnostics, more effective treatments, and potential cures for Wilson’s Disease.
Other Pages on Wilson’s Disease: