An international team led by Shinghua Ding at the University of Missouri has identified a rare genetic disorder called Mutation in NAMPT Axonopathy (MINA) syndrome, tied to a mutation in the NAMPT protein that undermines energy production in nerve cells and impairs motor function.
Scientists say the newly described MINA syndrome shows how a single genetic change can steadily erode movement. The condition stems from a mutation in NAMPT, an enzyme essential for cellular energy production through the NAD+ salvage pathway. When NAMPT falters, cells struggle to generate sufficient energy, and motor neurons—the nerve cells that relay signals from the brain and spinal cord to muscles—appear especially vulnerable.
Symptoms develop over time and can include muscle weakness, poor coordination, and foot deformities. In severe cases, people may ultimately need a wheelchair. “Although this mutation is found in every cell in the body, it seems to primarily affect motor neurons,” Ding said, adding that long nerve fibers and high energy demands may make these cells particularly susceptible.
The work builds on earlier research from Ding’s group. In 2017, a Cell Reports study from the team showed that loss of NAMPT in neurons triggers ALS-like paralysis and neurodegeneration in mice, highlighting the enzyme’s central role in neuronal health. That research prompted a medical geneticist in Europe to contact the Missouri lab after encountering two patients with unexplained movement problems.
By analyzing the patients’ cells and creating a corresponding mouse model, the researchers found the same NAMPT mutation driving disease biology in both cases. While mice carrying the mutation did not show obvious outward symptoms, their neurons displayed the same cellular defects seen in human cells—an example, the team said, of why patient-derived cells are crucial to understanding human disease. “Animal models can point us in the right direction, but human cells reveal what’s really happening in people,” Ding noted.
There is no cure yet for MINA syndrome. The researchers are testing ways to boost energy production in affected nerve cells, with the aim of slowing or stabilizing disease.
The findings were published in Science Advances on September 26, 2025, under the title “A sensory and motor neuropathy caused by a genetic variant of NAMPT.”
