Wilson's Disease–Conclusions and Proposals for Future Work

(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.

The figure above shows how gene transfer and hepatocyte transplantation come together as a treatment for Wilson's Disease (Original image from Google Images, modified and Annotated by KC)
Figure 1: The figure above shows how gene transfer and hepatocyte transplantation come together as a treatment for Wilson’s Disease (Original image from Google Images, modified and Annotated to pertain to Wilson’s Disease by KC)

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.

swi cu pbrain
Figure 2: The above figure shows an SWI Image of the brain of a patient with Wilson’s Disease. The areas circled in purple are the areas of interest for researchers studying the deposotion of copper in the deep grey nuclei of the brain. (Bai et al. 2014)


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:

Wilson’s Disease–Title Page

Wilson’s Disease–History and Metabolic Context

Wilson’s Disease–Molecular Basis of the Disease State

Wilson’s Disease–Treatments and Disease Management

4 Replies to “Wilson's Disease–Conclusions and Proposals for Future Work”

  1. Hi Kelly! I thought this, and your other pages, were well written and informative considering my lack of knowledge on Wilson’s Disease prior to reading your posts. Gene therapy, as you mentioned, could be a viable opportunity to cure WIlson’s Disease. Since it seems that the current methods for disease management in Wilson’s Disease are being scrutinized, mostly because of long term side effects, I was wondering if any researchers have thought of trying enzyme replacement therapy as a treatment. While this is similar to gene therapy, enzyme replacement therapy might be a useful backup plan if gene therapy proves to be unsuccessful. Unfortunately, this would not provide a cure for Wilson’s Disease and would simply be another management technique. What are your thoughts on enzyme replacement therapy for Wilson’s Disease? Would it be a worthy avenue to explore or do you think that gene therapy is our best bet at managing Wilson’s Disease?
    Thanks so much, and I am looking forward to your response.

    1. Hi Matt! Thank you for taking the time to read and comment! In my research I was expecting to find enzyme replacement therapy as an possible treatment option, but I didn’t come across much of anything. I think there may be a few reasons for this. First, ATP7B is a membrane bound protein, so I think enzyme replacement therapy may be a little more complicated here than it would be with a freely floating enzyme. Also, I thin because ATP7B mutation is fairly rare, there is not a lot of research into treatments for solely Wilson’s Disease. Many of the treatment options and research into potential cures is applicable either to several kinds of liver disease or to several kinds of copper transport and metabolism disorders. In this way researchers can get “more bang for their buck” if you will by developing treatment strategies for multiple rare diseases. It seems that gene therapy would inherently be more specialized to just ATP7B mutation and therefore only helpful for Wilson’s Disease patients and therefore may not be a big research focus right now. Thanks!

  2. Hi Kelly! Really excellent job on your entire website; I enjoyed reading it. I have a couple questions. First, hepatocyte transplantation seems like an intriguing pathway for Wilson’s Disease clinical trials to go down on. I’m just curious though- I know you said that one donor liver can provide hepatocytes for several transplants, but would this treatment really circumvent the liver donor problem? There will always be a limited number of donor livers, and since hepatocyte therapy is not yet a common treatment for Wilson’s, do you think that the limited number of donor livers available will impede clinical research regarding Wilson’s and hepatocytes?

    In addition, I know you mentioned that there is obviously less of a chance of rejection of hepatocytes than of a full liver, but has there been any documented rejection of hepatocytes? Are the symptoms severe, or is it something that could be tolerated with immunosuppressive drugs?

    Last, and this is more of a comment, but SWI is really cool- I don’t know if you know this, but are there any other diseases for which SWI is an experimental diagnostic tool?

  3. Hi Gabbie! Thanks for taking the time to read and comment! I think SWI is cool too! Right now it is mainly used to detect traumatic brain injury because it is so sensitive to venous blood. My understanding is that that was the purpose for which it was designed. However, now that they have noticed it picks up metal deposits so well it shows potential as a diagnostic for diseases involving metal deposition in the brain. To the best of my knowledge though, it is not currently used as a mainstream treatment to detect these diseases. In terms of hepatocyte tranplantation, there will likely still be a liver donor shortage for research and hepatocyte transplant and there is still risk of rejection and the need to take immunosuppressive drugs. However, all of these things are slight improved by using hepatocytes instead of a whole liver. When there is a donor liver, it goes farther in research and transplant because it can be used in multiple patients. The required dose of immunosupressive drugs is lower and the risk of rejection is less because the hepatocytes are being added to the existing liver and used to regenerate it. So, while all the issues are still there, they are of lesser magnitude, which is still a step in the right direction and the closest shot we currently have at a cure! Thanks!

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