Research Fund

Apart from The Kidney Dialysis Foundation’s (KDF) existing mission to look after the well being of kidney patients stricken with end stage kidney diseases, the Board of KDF has embarked on its next strategic mission to identify and support research work that lead to the prevention and cure of kidney failure due to diabetes and other complications. To facilitate this, the Memorandum and Articles of Association of the KDF was amended on 7 December 2006 and consent granted from the Commissioner of Charities on 15 March 2007. The Board of Directors on 25 May 2007 restricted fund designated “Research Fund” be set up.

The 1:1 government matching grant applied by the National University of Singapore has recently been approved and added to the KDF-NUS Research Fund. This would significantly aid us in making an important contribution in this area where the possibility of getting a new form of treatment for these patients is potentially in sight.

Areas of Research

As the cause of kidney failure in 50% of the new dialysis patients is due to diabetic complication of the kidney, a cure of diabetes will reduce the need for dialysis drastically. Through research, KDF aims to move up-stream and support research projects that will lead to the prevention of kidney failure and the need for expensive dialysis treatment. The other possible areas of research would be in area for alternative therapy to replace the existing dialysis treatment

Research Advisory Committee

To facilitate the review of research projects for their scientific and medical merits, the Board of Directors have commissioned the Research Advisory Committee to be set up under the Chairmanship of Prof Yap Kim Hui, Senior Consultant, Head, Division of Paediatric Nephrology, Immunology and Urology, National University of Singapore. Other members of the Research Advisory Committee include Associate Professor Lina Choong, Associate Professor Evan Lee and Dr Grace Lee.

Working Relationship with National University of Singapore

A working relationship is being established with the Yong Loo Lin School of Medicine, National University of Singapore, to provide the resources and infrastructure required to monitor and evaluate the progress of specific projects funded by the KDF Research Fund.  To achieve this, NUS and KDF have set up a Selection and Review Committee. This Committee comprises of Associate Professor George Yip, Assistant Dean (Grants) as the Chairperson and Professor Vathsala and Professor Yap Hui Kim as members for the period 2011 to 2015.

First Research Project Sponsored by the KDF-NUS Research Fund

KDF-NUS Gene Therapy and Cell Therapy 
The research aims to find cell that are readily available and get these cells to produce insulin. 
Umbilical cord cells 
The team has been working on cells from the umbilical cord. There is no problem with supply as umbilical cord is normally discarded. At the moment, these umbilical cord cells can grow and mature in the direction of the pancreas cells. There have been some success but the cells do not secrete insulin all the time. In one of the projects, the team has used a virus to put in the insulin gene so that these cells secrete insulin. When these cells were put into diabetic mice, these cells were able to lower the blood sugar and improve the diabetes. In these earlier experiments, these cells had an extra advantage in that they secreted a substance called HLA-G which would also prevent immune rejection – and so the mice did not need any of the anti-immune drugs that normally would be given to prevent rejection. This was the work of a student who has got her PhD, and the work was published in Cell Transplantation this year (2011). The team hopes to continue the next stage of the research with umbilical cord cells, with and without using a virus to put in the extra insulin gene. Ideally, if the cells can be made to secrete enough insulin when needed and to stop when there is no need for the insulin anymore. This fine regulation is essential. However, the results so far (which is similar to what other researchers are finding in other parts of the world); is that there is not enough insulin secretion and extra insulin from putting in the insulin gene by using a virus or using other techniques, is necessary. 
Bone Marrow cells 
The team is also working with two other laboratories on another source of cells from the bone marrow – mesenchymal stromal cells (MSCs). There is already a lot of experience with using bone marrow in the treatment of leukemia and other cancers. Obtaining bone marrow is almost a routine procedure in many medical centres. The team has been working on these cells with Professor M Ghoneim in Egypt, and with Professor Kon OL in the National Cancer Centre in Singapore General Hospital in getting these Bone Marrow MSCs to secrete insulin. Professor Ghoneim has already succeeded in getting rat bone marrow cells to secrete insulin and cure diabetes in mice. By working with Professor Ghoneim and Professor Kon on larger animals, the team hopes that together they shall be able to make some advances using larger animal models with diabetes. They hope to be able to treat some dogs with diabetes with dog bone marrow in the next stage of their research. 
The team is also working at the same time on human bone marrow MSCs to try to get these cells to secrete insulin with the fine regulation needed. The use of methods of culturing bone marrow MSCs that Professor Ghoneim has used in Egypt have had mixed results so far. The team hopes that in this next stage of the research, they shall be able to get these cells to make more insulin.
Updates – Interview with the NUS Research Team 
It’s a small team with a big dream – to find a cell or gene therapy for diabetes, which affects over 10 percent of the adult population in Singapore, and is a key cause of severe kidney disease requiring dialysis.
But the team of two NUS researchers – Dr Gan Shu Uin and Professor Lee K O – has, under the leadership of Sir Roy Calne, a pioneer in organ transplantation, and supported by a gift from the Kidney Dialysis Foundation (KDF), recently had some surprising success with their collaborators in Egypt: using human cells to cure diabetes in mice. Professor M Ghoneim’s team in Egypt is the first to demonstrate this important finding.
“This is an important step” says Sir Roy. "This is the only case of human bone marrow being used to cure diabetes in mice. I don't think there have been any other reports of that.” The NUS team has been collaborating with Professor M Ghoneim from the University of Mansoura in Egypt and Professor Kon Oi Lian from the National Cancer Centre at the Singapore General Hospital.
The procedure involves extracting mesenchymal stromal cells from human bone marrow, and growing ‘daughter’ cells that are taught to produce insulin. These can cure a diabetic mouse. One of the characteristics of these cells is that they not only produce insulin, they release insulin according to the requirements of the body.
The team is now keen to move a step forward from "the little mouse" says Sir Roy, and try treating dogs as dogs naturally get diabetes like humans. This procedure will involve the use of the human insulin gene in dog bone marrow cells. These insulin producing bone marrow cells will then be used to treat the diabetic dog.
So what does this mean for people suffering from diabetes? Is help at hand?
Sir Roy says, "If we can cure a diabetic dog, I think, though some people may disagree, that the argument for moving to clinical trials for people would be very strong. I would say, we should be trying the treatment on dogs within 18 months and if that works, we will look into the initiation and preparation of clinical trials."
The mood is one of cautious optimism, the team agrees. As Sir Roy says, “In science one trips up. You think you know where you are going, but there is a brick on the road.” There are many unknowns, he says. "We don't know if it will work in man as a dog eats once a day while man eats three meals, and are we going to produce enough insulin at the right time to stop the secondary complications like blindness, heart failure, kidney failure..." These are just some of many concerns.
This work involving dogs will be carried out in collaboration with veterinarian Dr Robert Foale, who is an expert in diabetes in dogs, and Professor Andrew Lever from University of Cambridge making this a three-continent collaboration - Singapore (Asia), Cambridge (Europe) and Egypt (Africa).
"This would have been impossible without Sir Roy," says Prof Lee. "Through his connections, his friendships he was able to bring us all together and get this done.”
Dr Gan adds, “Scientists often work in their own little niche, but with Sir Roy’s help, our little group has the advantage of collaborative work – with scientists, clinicians, veterinarians. We learn from each other’s experience. Each collaborator brings their unique perspective and this enables us to see the problem in a holistic manner rather than just at the cellular level.”
The breakthrough in this research locally would not have been made possible without KDF donors. Both KDF and NUS would like to thank all supporters that have played the vital role in this project, and have helped to keep this dream of preventing kidney failure alive.

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About Us

The Kidney Dialysis Foundation (KDF) is a non-profit charitable organisation, established in February 1996.

KDF provides subsidised dialysis treatment to needy members of our community so that these patients will not be deprived of treatment.

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