Scientists Discover New Genetic Disease behind Mysterious Muscle Weakness

An international team of researchers led by Shinghua Ding at the University of Missouri has discovered a new genetic disorder that interferes with muscle control and movement, the journal Science Advances reported.

The condition, known as Mutation in NAMPT Axonopathy (MINA) syndrome, damages motor neurons, which are the nerve cells responsible for transmitting signals from the brain and spinal cord to muscles. It develops from a rare mutation in a key protein called NAMPT that supports the body’s ability to produce and use energy. When this protein malfunctions, cells cannot generate enough energy to maintain normal function.

As energy levels drop, affected cells gradually weaken and die, leading to symptoms such as muscle weakness, coordination problems, and foot deformities that can become more severe with time. In advanced cases, individuals may lose mobility and require the use of a wheelchair.

“Although this mutation is found in every cell in the body, it seems to primarily affect motor neurons,” Ding, a professor in Mizzou’s College of Engineering, said. “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.”

This discovery builds on years of foundational research by Ding and his collaborators.

In 2017, Ding published a landmark study showing that NAMPT is critical for maintaining healthy neurons. He found that a lack of NAMPT in nerve cells leads to paralysis and symptoms similar to ALS, a well-known motor neuron disease.

That finding caught the attention of a medical geneticist in Europe, who later reached out to Ding after seeing two patients with unexplained muscle weakness and coordination issues. The doctor asked if Ding’s team could investigate.

Ding and collaborators studied the patients’ cells and a mouse model. They found both patients had the same NAMPT mutation, confirming it was the cause of the disease. Interestingly, the mice carrying the mutation did not show visible symptoms, but their nerve cells displayed the same internal problems seen in the human 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.”

While there’s no cure yet for MINA syndrome, researchers are already testing ways to boost energy levels in affected nerve cells.

This research marks a significant step forward in understanding rare genetic diseases and how disruptions in cellular energy metabolism can affect nerve health. It also demonstrates how basic scientific research can lead to discoveries that have direct implications for patients living with rare, unexplained conditions.

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