Erythrocyte Encapsulated Thymidine Phosphorylase in MNGIE Patients
Research type
Research Study
Full title
A Multi centre, Multiple dose, Open label Study to Investigate the Safety, Tolerability, Pharmacodynamics, and Efficacy of Erythrocyte Encapsulated Thymidine Phosphorylase (EE TP) in Patients with Mitochondrial Neurogastrointestinal Encephalomyopathy (MNGIE)
IRAS ID
253249
Contact name
Niranjanan Nirmalananthan
Contact email
Sponsor organisation
St George's University of London
Eudract number
2018-003000-39
Duration of Study in the UK
2 years, 5 months, 0 days
Research summary
Mitochondrial-Neurogastrointestinal-Encephalomyopathy (MNGIE) is a disease which affects the digestive and nervous systems. MNGIE leads to nutritional failure and muscular disability causing death around 38 years old. MNGIE results from a mutation in the TYMP gene which codes for thymidine phosphorylase (TP), the enzyme responsible for breaking down thymidine and deoxyuridine. This leads to accumulation of thymidine, deoxyuridine and damage to DNA found in mitochondria (mtDNA). Mitochondria are structures within cells responsible for generating energy. Mutations accumulate in mtDNA affecting mitochondrial function.
There are no specific treatments for MNGIE whose effectiveness has been evidenced in clinical studies.
The treatment is made by taking about 1 cup of blood form the patient, the drug substance (functional) TP is inserted into the patient’s own red blood cells using a red cell loader to form the treatment EE-TP which is then administered back into the patient via infusion. This prolongs the half-life and will potentially minimise immune reactions. Thymidine and deoxyuridine crosses cell membranes and exists in equilibrium between the cell and plasma. Strategies that reduce the concentrations of plasma thymidine and deoxyuridine may be beneficial to patients with MNGIE. The development of enzyme replacement therapies have successfully treatment of other inherited metabolic diseases. The administration of the missing enzyme enables the elimination of the pathological substrates that accumulate in these metabolic disorders, translating into clinical benefit.
This is a Multi-centre, Multiple dose, Open label Study to Investigate the Safety, Tolerability, Pharmacodynamics, and Efficacy of EE-TP in Patients with MNGIE. The study will enrol 12 adult treatment naïve adult patients with MNGIE, and a further 8 adolescent/paediatric patients. All patients will be administered EE-TP. EE-TP will be administered every 3 weeks until metabolic correction is achieved. From Day 78 it is planned that patients will receive EE-TP every 2 to 4 weeks for 22 months.REC name
South West - Central Bristol Research Ethics Committee
REC reference
18/SW/0266
Date of REC Opinion
9 Jan 2019
REC opinion
Further Information Favourable Opinion