Update: January 2013
Despite the holiday period, the PKU Research Team has continued to beaver away at our projects.
PKU Gene Research:
One of our PhD Scholars, Gladys Ho, has just had her final PhD thesis examined, and it was passed with flying colours! Gladys' work included extensive testing of the PAH gene in individuals with PKU seen at the clinic at the Children's Hospital. As expected, Gladys found that many of our patients have gene mistakes that have been reported before, but she also discovered some gene mistakes that have never been reported before. Of particular interest, using a test tube based system, she was able to study the functional consequences when two different mistakes are together, which is the situation we see in most patients with PKU. We hope to write up her novel findings for publication in the very near future. In addition, Gladys studied the potential usefulness of a class of drugs to correct a specific type of gene mistake seen in about 10% of people with PKU, so-called nonsense mutations. Her studies have provided evidence that new improved versions of these drugs could one day have a place in the clinic. A manuscript relating to this work is currently under review by a research journal.
Unfortunately for us, Gladys has to move on to other research, and we wish her every success in her future endeavours!
GM Probiotic Research:
Work continues in the development and testing of this potential new therapy for PKU. I was given the honour of presenting our proof-of-principle data at the prestigious American Society of Human Genetics Conference in San Francisco in November, which was very well received. In fact, there has been interest pressed by several pharmaceutical companies, and I am currently in discussion with them about potential clinical trials, which admittedly are at least 18 months away.
For now though there is still much work that needs to be done in the test tube and in our PKU mice to gather stronger evidence in support of the GM probiotic as a therapy for PKU. More recent experimental has shown that:
in the test tube our GM bug is able to clear phenylalanine much faster at 37oC than at 4oC, but that it is still stable at the lower temperature. This will hopefully mean that in the future it can be stored in the fridge, taken cold, and then when it gets to body temperature will be able to do its job.
if we give the GM probiotic to mice with milk this helps protect the bug from attack by acids in the stomach and digestive in the gut. We think we can do better than that, and Dr Tong continues to work on potential genetic modifications to further improve the resilience of the bug in the gut.
To date, most of our mouse experiments have been done when they are given free phenylalanine in solution, which is the simplest experimental system. We are now preparing some specialised reagents which cannot be bought "off the shelf", so that we can test the capacity of our GM probiotic to break down and clear phenylalanine that is actually contained within protein. This will be the "make or break" experiment. If it works efficiently on intact protein, then this will be our best evidence yet, and will push things along one step closer to future trials in PKU patients.
So, watch this space …