Table 1.
Exogenous stem cell therapy for nuclear gene mutations in MNGIE
| Reference | Age/Gender | Intervention | Outcome measures | Outcome | Reported adverse events |
|---|---|---|---|---|---|
| Hussein 2013 | Patient 1: M/24 | HLA fully matched BMT | TP activity | TP activity initially rose from 1 to 180 nmol/h/mg/protein but then dropped to 10 nmol/h/mg/protein 10 months post-transplantation. | GVHD |
| dThd and dUrd levels | Normalized. | ||||
| Clinical condition | Subjective improvement in walking, hearing, abdominal pain, dysphagia, vomiting and diarrhoea and weight gain 3 months post-transplantation. No improvement in peripheral neuritis or foot drop. | ||||
| Filosto et al., 2012 | Patient 1: F/34 | HLA matched HSCT | TP activity | Patient 1 and 2: TP activity rose from 0 nmol/h/mg/protein to within normal range. | Patient 1: Pyrexia of unknown origin, hyperglycaemia, pancreatitis, CMV reactivation, GVHD and complications of immunodeficiency. |
| Patient 2: F/22 | Clinical condition | Patient 1: no improvement in neurological assessment, nerve conduction studies or gastrointestinal symptoms. Patient died 15 months post-transplantation. | Patient 2: mild GVHD. Posterior reversible encephalopathy syndrome and C. difficile diarrhoea, followed by septic shock and ARDS. | ||
| Patient 2: reduced gastrointestinal discomfort but no improvement in neurological symptoms. Died 8 months post-transplantation. | |||||
| Sicurelli et al., 2012 | Patient 1: F/23 | HLA matched HSCT | TP activity | TP activity rose from 0 nmol/h/mg/protein to within normal range. | Worsening of sensory neuropathy. |
| dThd and dUrd levels | dThd and dUrd levels normalized. | ||||
| Blood lactate | Blood lactate decreased from 2.3 to 1.5 mmol/l. | ||||
| Clinical condition | Resolution of diarrhoea, vomiting and pain and fatigability 1 month post-transplantation. MRC muscle strength score increased by 16 points and proximal motor conduction velocities improved 12 months post-transplantation. Sensory neuropathy worsened and MRI defined leukoencephaolopathy was unchanged. | ||||
| Hirano et al., 2006 | Patient 1: F/21 | HLA matched placental cord blood transplant | TP activity | Patient 1 and 2: TP activity increased to peaks of 104 and 165 nmol/h/mg/protein after 1-2 months in patient 1 and 2 respectively but then decreased. | Patient 1: non-engraftment. |
| Patient 2: F/30 | HLA matched related SCT | dThd and dUrd levels | Patient 1 and 2: dThd and dUrd levels were reduced in both patients and to within normal range for patient 2 after 2 months. | ||
| Clinical condition | Patient 1: No symptomatic improvement was documented. Died 86 days Post-transplantation from disease progression. | ||||
| Patient 2: subjective improvement in abdominal pain, swallowing and distal limb numbness 6.5 months post-transplantation. Biceps and ankle reflexes returned | |||||
| Lenoci et al., 2011 (abstract only) | Patient 1: F/21 | HLA matched related HSCT | TP activity | TP activity normalized 55 days post-transplantation. | None reported. |
| dThd and dUrd levels | dThd and dUrd levels decreased. | ||||
| Clinical condition | Subjective improvement in vomiting, diarrhoea and abdominal pain with increase in body weight. No improvement in neurological symptoms was documented. | ||||
| Hill et al., 2009 | Patient 1: F/41 | HLA matched related peripheral blood SCT | TP activity | TP activity normalized by day 25 post-transplantation and was still normal 14 months post-transplantation. | Idiopathic thrombocytopenic purpura and gastrointestinal haemorrhage. |
| Clinical condition | Improvement in oral intake and increase in weight. Neurological performance status, repeat EMG and cerebral MRI scan were unchanged. |
A series of case reports of stem cell therapies in eight patients with MNGIE showed variable results. Overall thymidine phosphorylase activity tended to increase post-transplantation and some improvements in gastrointestinal and neurological symptoms were reported.
ARDS = acute respiratory distress syndrome; BMT = bone marrow transplant; CMV = cytomegalovirus; EMG = electromyogram; F = female; GVHD = graft versus host disease; HLA = human leukocyte antigen; HSCT = haematopoietic stem cell transplantation; M = male; MRC = Medical Research Council; SCT = stem cell transplant; TP = thymidine phosphorylase; dTHd = thymidine; dURD = deoxythymidine.