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Rare Diseases February 2019

Enzyme replacement therapy approved for UK clinical trials


Dr Bridget Bax

Reader in Rare Diseases St George’s, University of London

Researchers at St George’s University of London are developing an enzyme replacement therapy for MNGIE (mitochondrial neurogastrointestinal encephalomyopathy), a progressive disorder where patients die at an average age of 35 years.

Patients with MNGIE have a defect in the gene that codes for the enzyme, thymidine phosphorylase and results in affected individuals producing insufficient enzyme. Thymidine phosphorylase is required for the normal metabolism of substances called thymidine and deoxyuridine. In its absence, these accumulate to toxic levels in the body, causing damage to the mitochondria, which are the powerhouses of the cell. Tissues that are heavily dependent on energy, such as muscle, the gastrointestinal system and nervous system are severely affected.

The St George’s team, led by Dr Bridget Bax (with Drs Michelle Levene and Niranjanan Nirmalananthan) are investigating the effectiveness of using the patient’s own red blood cells (erythrocytes) as a vehicle to carry the missing thymidine phosphorylase in the blood circulation. The erythrocytes provide a protected environment in which the enzyme can function. The encapsulated enzyme reduces the levels of toxic metabolites in the blood, relieving the nervous system and muscle of their damaging effects.

Data obtained from the compassionate use of erythrocyte encapsulated thymidine phosphorylase (EE-TP) in patients with MNGIE showed that a reduction in blood thymidine and deoxyuridine levels can be causally linked to clinical benefit. EE-TP has been approved by the Medicines and Healthcare products Regulatory Agency (MHRA), clearing the way for patient clinical trials to begin this year. The team are now applying for approval to extend trials to other countries.

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