Dr Nathan Davies
Lecturer in biochemistry at the Institute of Hepatology, University College London.
Dr Nathan Davies is working with the company Gambro to develop a new type of liver dialysis. The MRC is funding the research through an MRC Industry Collaboration Award (MICA).
The body’s kidneys and liver are responsible for the removal of toxic or unwanted substances from the blood. If they are damaged, one treatment option is to do their job for them: take the patient’s blood outside their body and use an artificial filter. This process is called dialysis.
Replicating kidney function is relatively straightforward and kidney dialysis is well established in the clinic. The liver’s job is more challenging: it removes substances that do not dissolve in water or that require metabolism first, so it is no simple filter. Liver dialysis has been pursued for many years, however, and a commercial design using albumin was developed in the early 2000s. Albumin has many important functions, including transporting substances in the blood. Putting albumin on one side of the membrane and the patient’s blood on the other created a concentration gradient that pulled protein-bound toxins from the blood into the albumin.
The device was used in a multi-centre trial, partly conducted at UCL. When the researchers looked at the results, they saw that although the system worked to remove protein bound substances, the liver patients were not getting better. After further study, the UCL researchers came to the conclusion that a key factor was that the patients’ own albumin was not working properly. The more severe the liver condition, the less albumin the patient had, and what albumin they did have functioned poorly. This meant that toxins stayed in the patients’ tissues rather than being transported in the blood to either the liver or the dialysis machine.
Dr Nathan Davies and colleagues have been working on a new version of liver dialysis. The first component of their device replaces the patient’s albumin. By removing poorly functioning albumin, they take out any toxins that are bound to it and reduce the risk that damaged albumin may itself pose to the patient. They then replace it with normal albumin, which is readily available as an ‘off the shelf’ plasma product.
Liver patients are susceptible to infection and studies at UCL have shown that they are especially at risk due to inflammation caused by bacterial endotoxins. So the new device also includes a specific filter to remove endotoxins – this approach is used to treat sepsis but it has not been combined with liver dialysis before.
In 2006, multinational dialysis company Gambro had bought out the company behind the liver dialysis machine that had been tested at UCL. When the idea for UCL’s new liver dialysis device came up, they approached Gambro for support to help build a prototype. Gambro agreed, bringing the technological know-how and component manufacture capability the UCL researchers needed.
“It is fantastic to be able to access their practical expertise,” says Dr Davies. “The MRC funding allows the academic side of the collaboration to work. With that in place, we can get the in-kind support from the company, including components and their time and practical expertise.”
Now the team is examining each component of the device to see where it could be further improved. This will lead to a final design which can be tested in models. After that, the next stage will be trials in human patients. “From a university perspective,” says Dr Davies, “if you want to see something taken on and become a success, then finding someone with the resources to do it is great. The MRC funding is ideally suited for this project. It’s the right scheme at the right time, filling the gap between proof-of-concept and the phase when we’re ready to push into trials and marketing.”
Published July 2011