St George's, University of London has signed an exclusive worldwide licensing agreement with rare-disease research-and-development firm Orphan Technologies Ltd to develop new therapies for deadly metabolic disorders.
St George's and Orphan aim to develop therapies based on an innovative and highly specialised cell-based enzyme-replacement technology, called Erythrocyte Encapsulated (EE) technology.
Their primary goal is to accelerate the development of an investigational therapy for mitochondrial neurogastrointestinal encephalomyopathy (MNGIE), a progressive disease that kills patients at an average age of 38. Upon approval, the new enzyme-replacement therapy would be the first approved drug treatment for a mitochondrial disease.
MNGIE is caused by a defect in the gene responsible for production of the enzyme thymidine phosphorylase (TP). Without this enzyme, mitochondria - the parts of the body's cells that create energy for the cells - cannot function properly, leading to problems with the nervous system and skeletal muscle. Symptoms of MNGIE include diarrhoea, constipation, gastroparesis, nausea, vomiting, weight loss, muscle weakness and nerve damage leading to loss of sensation and abnormal eye movements.
Globally, only 200 cases of MNGIE have been identified, but these are increasing and experts believe it has been underdiagnosed. The only current potential cure is a stem cell transplant technique, but this carries a high risk of death and most patients are ineligible as recruitment is restricted only to those with an optimal matched donor and without irreversible end-stage disease.
The investigational therapy for MNGIE is called Erythrocyte Encapsulated Thymidine Phosphorylase (EE-TP), which is based on introducing TP directly into patients' red blood cells (erythrocytes). This encapsulation technology has the advantages of increasing the period the enzyme is most effective for and minimising immunogenic reactions.
Several patients with urgent medical needs have already been effectively treated with EE-TP through compassionate use treatment. Administration of EE-TP was reported to be effective in reducing or eliminating the elevated plasma and urine concentrations of thymidine and deoxyuridine, toxic substances that accumulate in tissues of MNGIE patients. Clinical improvements have also been reported, with a reduction in the number of nausea and vomiting attacks, a reduction in weight loss, and an improvement in distal sensation in hands and fingers.
Dr Bridget Bax, head of the St George's team and one of the world's leading authorities on MNGIE, said: "MNGIE is a relentlessly progressive degenerative disease and for a majority of patients there are no treatment options other than supportive care. Our team is committed to addressing the unmet needs of these patients.
"Under the licensing agreement with Orphan, we intend to combine our strengths to accelerate the regulatory development of EE-TP. Our ultimate hope is that EE-TP will benefit patients with MNGIE and that patients globally have equitable access."