Non-Ketotic Hyperglycinemia, (NKH), is a rare, genetic disorder that affects only one child in every 60,000.
It is caused by an excess of glycine on the brain that affects development.
The condition can vary in severity, with the more severe forms resulting in frequent seizures, immobility, and global developmental delay.
The condition is life-limiting, and there are only approximately 15 children in the United Kingdom and 500 children worldwide still surviving with NKH.
Huge strides are being made into understanding NKH and what makes our children so sick. MRI scans have been studied and the many genes that can cause the disorder have been mapped. We are now heading towards gene therapy, and a clinical trial is hopefully soon on the horizon.
Joseph’s Goal currently financially supports the research of Dr Johan Van Hove at the University of Colorado, Denver, USA, and Professor Nick Greene at UCL Great Ormond Street Institute of Child Health in London.
Excitedly, more NKH researchers are now coming forward, notably Boston Children’s Hospital and Dr Kasturi, who is based in Chicago.
At last, there appears to be some light at the end of a very dark tunnel.
Please click for additional information about NKH from Van Hove and Professor Greene.
Research on NKH by Dr Johan Van Hove at the University of Colorado, Denver USA
Dr Johan Van Hove, when we started fund-raising, was the world leader in NKH research.
His time and dedication to researching NKH is amazing and the families around the world are staggered at how much he has achieved in a relatively short amount of time.
We are proud to have given so much of our fundraising efforts to such a dedicated researcher. Our financial support has enabled him to employ further researchers in his lab and to understand NKH.
NKH is such a rare condition that Dr Van Hove’s first task was to determine what makes the brain so sick in a child with the disorder. Secondly, he undertook the huge ordeal of comparing the MRI scans of NKH children around the world and mapped the many varied genes that can cause the disease and how these genes can predict the severity of the illness.
Finally, he aims to review what the impact has been of the current existing treatment on the patients.
‘We hope that this will provide the way with which we can develop a treatment that changes the course of the disorder for these unfortunate children.’
Since Dr Van Hove started researching NKH, other research doctors from around the world have also taken an interest in this cruel and devastating disorder.
Research on Non-Ketotic Hyperglycinemia at UCL Great Ormond Street Institute of Child Health
The research group at University College London, led by Prof. Nick Greene, is focusing on studies to better understand the disease process of NKH and to develop new therapies. NKH is caused by a genetic defect that affects a protein complex in the body called the glycine cleavage system. This prevents the breakdown of a small molecule called glycine, which then accumulates to harmful levels in the body.
One hindrance in NKH research has been the lack of an experimental system. For this reason, the UCL group developed a mouse model, with disruption of the mouse equivalent of the gene which is most commonly defective in children with NKH. The mice show features of NKH such as elevated glycine and a range of approaches are now being used to study this model in more detail. For example, sensitive biochemical measurements have shown changes in particular aspects of metabolism. EEG is being used to ask whether NKH mice show altered brain electrical activity and the brain cells are being analysed in to ask where the injury occurs. Importantly, as well as generating new information on the disease process, these studies provide measures for assessing the effects of potential new treatments, such as new or untested drugs. For example, existing NKH treatments such as benzoate have been tested and other approaches are now being investigated.
A major line of research aims to make progress towards gene therapy for NKH. Mouse genetic tools are being used to restore expression of the glycine cleavage system gene in particular tissues and at different stages of development in the NKH mice, to ask whether this ‘rescues’ the disease. These experiments are a step towards testing gene therapy, in which a normal copy of the glycine cleavage system gene is introduced into the NKH mice. These tests are now in progress – if successful, this approach could potentially be developed for use in children with NKH.
In addition to the mouse models, the UCL group are also working to develop new models in zebrafish and in cell lines, each of which has advantages for asking particular research questions. Details on Prof. Greene’s research and publications can be found below.