A global team of researchers led by Shinghua Ding at the University of Missouri has discovered a new genetic disorder that interferes with muscle function and movement control.

The condition, known as Mutation in NAMPT Axonopathy (MINA) syndrome, harms motor neurons – the nerve cells responsible for transmitting signals from the brain and spinal cord to the body’s muscles. It stems from a rare mutation in the NAMPT protein, which plays a crucial role in helping cells produce and use energy. When this protein malfunctions, cells cannot generate the energy they need to survive and perform properly.

How Energy Failure Affects the Nervous System

As the energy deficit worsens, cells gradually weaken and die, leading to symptoms such as muscle weakness, poor coordination, and deformities in the feet. These symptoms typically progress over time, and in the most severe cases, individuals may eventually require a wheelchair.

“Although this mutation is found in every cell in the body, it seems to primarily affect motor neurons,” Ding explained. “We believe nerve cells are especially vulnerable to this condition because they have long nerve fibers and need a lot of energy to send signals that control movement.”

Building on Years of Foundational Research

The new finding expands on earlier research conducted by Ding and his team. In 2017, they published a pivotal study showing that NAMPT is vital for keeping neurons healthy. Their work revealed that losing NAMPT function in nerve cells can lead to paralysis and symptoms resembling amyotrophic lateral sclerosis (ALS), a well-known motor neuron disease.

This earlier study drew the attention of a medical geneticist in Europe who had encountered two patients with unexplained muscle weakness and coordination problems. Seeking answers, the doctor contacted Ding’s lab to investigate the potential connection.

Confirming the Genetic Cause

By analyzing cells from the patients and creating a corresponding mouse model, Ding and his collaborators confirmed that both patients shared the same NAMPT mutation responsible for their symptoms. Interestingly, although the mice carrying the mutation did not display outward physical symptoms, their nerve cells showed the same internal cellular defects seen in the patients’ cells.

“This shows why studying patient cells is so important,” Ding said. “Animal models can point us in the right direction, but human cells reveal what’s really happening in people.”

Toward New Treatments and a Deeper Understanding

There is currently no cure for MINA syndrome, but researchers are already exploring methods to boost energy production in affected nerve cells.

The discovery represents a major advance in understanding rare genetic conditions and illustrates how problems in cellular energy production can lead to nerve damage. It also highlights how years of basic laboratory research can ultimately lead to breakthroughs that provide real hope for patients with rare and unexplained diseases.

The findings were published in Science Advances under the title “A sensory and motor neuropathy caused by a genetic variant of NAMPT.”