Table 2.
New protein delivery to treat MNGIE
| Reference | Age/gender | Intervention | Outcome measures | Outcome | Reported adverse events |
|---|---|---|---|---|---|
| Bax et al., 2013 | M/28 | Encapsulated TP | Plasma dThd and dUrd levels between cycles | Thd and dUrd levels reduced to 8.1 and 12.6 mmol/l from 20.5 and 30.6 mmol/l, respectively after 27 cycles. | Mild transient reaction to infusion with coughing and head and neck erythema. |
| Urinary dThd and dUrd levels between cycles | Urinary dThd and dUrd levels reduced to 192–282 and 0.0–184 mmol/24 from 421 and 324 mmol/24 h, respectively from cycle 21. | ||||
| Plasma creatine kinase | Creatine kinase level reduced from 1200 U/l pre-therapy to 254 U/l (normal range 40–320 U/l) at 23 months. | ||||
| Clinical condition | Increase in MRC power sum score 56 (baseline) to 74 (23 months post-infusion). Improvements in gait, balance, sensory ataxia and finger dexterity. Weight increased from 57.4 kg (baseline) to 61.2 kg (post-infusion). No change in EMG or nerve conduction studies. Patient self reported an increased walking distance from 1 to 10 km. | ||||
| Moran et al., 2008 | F/21 | Encapsulated TP | Plasma dThd and dUrd levels | 3 days post-infusion plasma dThd and dUrd levels reduced (but not to within normal range) but then began to rise. | |
| Urinary dThd and dUrd levels | 3 days post-infusion urinary dThd and dUrd levels fell to 6% and 13% of the pre-therapy values respectively (these values were still not within normal range). | None reported. | |||
| Clinical condition | Clinical condition remained poor and the patient died 21 days post-infusion. |
Systemic protein delivery: thymidine phosphorylase (TP) encapsulated in erythrocytes. Thymidine phosphorylase can be encapsulated in autologous blood erythrocytes by reversible hypo-osmotic dialysis, these erythrocytes can then used for infusion to increase the functional thymidine phosphorylase levels of the recipient. Results from two case reports of infusion of thymidine phosphorylase encapsulated in erythrocytes for patients with MNGIE demonstrated initial reductions in toxic product levels post transplantation and some reported clinical improvement. MRC = Medical Research Council; dTHd = thymidine; dURD = deoxythymidine.