We've launched a partnership to develop a new enzyme replacement therapy

We’re really pleased to say that the AKU Society has launched a partnership with Protein Technologies Ltd, a bio-tech start-up, to develop a new model of enzyme replacement therapy for AKU that could have positive implications for many other rare diseases.

In the first of a series of studies, Protein Technologies Ltd will be producing a range of recombinant mutants of homogentisate 1,2-dioxygenase (HGD  – the deficient enzyme in AKU) and test them in vitro and in vivo in mice models for their effects on homogentisic acid (the damaging substance in AKU). Using site-directed mutagenesis techniques and its proprietary unnatural protein technology, Protein Technologies Ltd will seek to prove that a recombinant HGD can be synthesized which is more active and more stable than the naturally occurring enzyme.

This work will be in close collaboration with our scientific team at the University of Liverpool. We’re extremely excited about this project. If successful, it will open up a new avenue of potential treatment not just for AKU, but for a wide range of other rare diseases caused by deficient enzymes.

For more about Protein Technologies Ltd, read this article entitled “Project ‘could be as revolutionary as silicon chip’”: http://menmedia.co.uk/manchestereveningnews/news/business/s/1408919_project_could_be_as_revolutionary_as_silicon_chip.

Here’s what the enzyme, homogentisate 1,2-dioxygenase (HGD), looks like:

HGD enzyme

 

This is very exciting work for us. More than 65 mutations in the homogentisate oxidase enzyme (HGO) gene have been identified in people with AKU. It is widely believed that these mutations result in disruption of the structure and function of the HGO enzyme, thereby increasing the levels of homogentisic acid, which is the molecule causing the damage in AKU.

HGO is expressed mainly in the liver and kidneys. A promising strategy for the treatment of AKU is therefore administration of a recombinant version of HGO that can restore HGA to normal levels. Such a recombinant HDO analogue must be active enough to break down HGA but not so active as to bring about tyrosinemia (i.e. high levels of tyrosine in the blood). Longevity of action is also important as is the route of administration which, in addition to injection or nano-needle array, could also potentially include include oral, topical and inhalation.

 

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