Prior to this lecture at Oxford, my understanding of KD has been superficial but after reading an explanation by Dr Fischbeck and attending his lecture at Oxford University I have a much better grasp.
We have a repeat of a CAG pattern in the Androgen Receptor gene on our X chromosome. If one has up to 36 repeats you will not have KD but 38 and above you will and generally the more repeats the earlier the onset and severity. These extra repeats cause us to produce a longer Androgen Receptor protein which isn’t good but in itself would not cause KD, it is the toxicity it causes to the neurons and muscle cells this in turn damages the cells and ultimately results in the death of these cells. Below is the more technical description, took me several hours and Wikipedia to get a basic understanding.
So what is happening in the world of research regarding treatment? Well there are research groups in America, Copenhagen, Padua, Nagoya and here in London and Oxford. There is research mainly in five areas.
Testosterone assists in the process of this toxic damage so they have been looking at reducing the level of testosterone. Trials have taken place in Japan and in the USA but the results show only small gains and unfortunately the side effect is to decrease the patient’s quality of life. They have not abandoned this line of research but are trying to refine the reduction of the androgen to affect targeted areas only.
A drug used for prostate cancer HSP90 (heat shock protein) has also been tested because it increases or enhances cellular protection and reduces the toxic effect. This has worked in mice; a trial is planned with patients.
We lose muscle strength due to the toxic effects and ways to strengthen muscles was investigated, but it was found that exercise was the least invasive and produced similar results to drugs used. So regular aerobic exercise is highly recommended, but care should be taken not to overdo exercise as this is detrimental to the muscles of a KD sufferer.
Another avenue being explored is injections of micro RNA focusing at altering the RNA to stop producing the mutant protein, has worked in mice, but in humans?
Lastly Dr Fischbeck is working with groups on a synthetic curcumin which show good lab results in reducing toxicity and strengthening the x cells ability to resist. We asked how this research was going and was told trials possibly in the UK would start in the near future. It was stated many times during the lecture that intervention at an early stage gave better results. So I asked what at 63 could I expect if trials went well, he stated he believed I could regain some of my strength.
I had thought that no treatment would be available in my lifetime hopefully I will be proved wrong. To finish, Dr Fischbeck said our best tool for overcome this disease is Hope.
Dr Kenneth Fischbeck is one of the leading figures in KD research. Colin attended Dr Fischbecks lecture as a representative of KD-UK in June. Colin, along with his two brothers, is a KD sufferer himself.