Blood Cell Infusions Helpful in MNGIE

Infusions of either mature blood cell fragments (platelets) or blood stem cells from healthy donors partially corrected biochemical abnormalities in three out of four patients with the mitochondrial disease MNGIE.

In this disease, mutations in the gene for the thymidine phosphorylase (TP) enzyme severely reduce its ability to metabolize thymidine and deoxyuridine, which accumulate to toxic levels and damage mitochondria, the energy-producing units of cells.

MDA grantee Michio Hirano at Columbia University in New York was involved in both studies, results of which were published Oct. 24 in Neurology.

The researchers reasoned that supplying patients with TP-producing blood cells from donors might normalize the chemical environment and reduce damage to mitochondria.

They infused (introduced through a blood vessel) mature, TP-producing platelets into a 23-year-old woman and a 16-year-old boy with MNGIE. In both cases, the infusions briefly increased TP levels and reduced levels of thymidine and deoxyuridine, although the patients’ symptoms didn’t improve.

The infused TP apparently doesn’t have to enter muscle cells to be effective; it only has to be in the vicinity to lower the potentially damaging compounds.

They next tried infusing stem cells from donors, with the hope that these cells might permanently establish themselves in the circulation (engraft) and continuously produce TP.

When umbilical cord stem cells were infused into a 21-year-old man with severe MNGIE, they failed to engraft. But when a 30-year-old woman with MNGIE received blood stem cells from her healthy brother, some of them engrafted, and she experienced less abdominal pain, better swallowing, and decreased numbness in her hands and feet.

The researchers note that direct administration of stabilized TP protein or perhaps gene therapy with the TP gene might be more effective treatments than cell infusions. They added that treatment should begin as early after diagnosis as possible, before irreversible damage to the mitochondria occurs.