Researchers diagnose previously unknown cellular health condition called MINA syndrome

Deep inside your nervous system, a tiny fault in how cells make energy can quietly change the course of a life. That hidden glitch is at the heart of a newly identified genetic disease that slowly weakens muscles and movement, and it has given scientists a rare window into how fragile your motor nerves really are.

An international team led by Shinghua Ding at the University of Missouri has described a previously unknown condition called Mutation in NAMPT Axonopathy, or MINA syndrome. The disorder stems from a rare change in a gene that encodes NAMPT, a protein your cells rely on to make and recycle energy molecules.

NAMPT helps build NAD+, a crucial chemical that keeps your mitochondria working. Those tiny structures inside cells act like power plants. When NAMPT falters, NAD+ levels drop, and cells struggle to produce enough fuel to stay healthy.

That shortage hits motor neurons especially hard. These are the long nerve cells that carry signals from your brain and spinal cord to your muscles. When they begin to fail, everyday tasks, from walking across a room to lifting a foot, slowly become more difficult.

Over time, people with MINA syndrome develop muscle weakness, balance problems, and deformities in the feet. Symptoms can worsen as the years pass. In severe cases, someone may eventually need a wheelchair to get around.

“Although this mutation is found in every cell in the body, it seems to primarily affect motor neurons,” Ding 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.”

The story of MINA syndrome began long before any patient had a name for their condition. In 2017, Ding and colleagues showed that NAMPT is essential for keeping neurons alive in animal models. When they removed this protein from nerve cells, the animals developed paralysis and signs that looked similar to amyotrophic lateral sclerosis, or ALS.

That result caught the attention of a medical geneticist in Europe who was treating two siblings with unexplained muscle weakness and poor coordination. Their symptoms did not match known disorders. After reading Ding’s earlier work, the physician wondered if NAMPT might be involved and reached out to his team.

The collaboration brought together careful clinical observation and deep lab expertise. Researchers analyzed the siblings’ DNA and found that both carried the same rare change in the NAMPT gene. The mutation alters a single building block in the protein, enough to disrupt its function.

To test whether this variant truly caused the disease, the team studied cells taken from the patients and created a mouse model carrying the same genetic change. That work confirmed that the NAMPT mutation was not just a random finding. It lay at the center of the nerve damage.

In cells from people with MINA syndrome, NAMPT’s enzyme activity was clearly reduced. With that drop came lower NAD+ levels and sluggish energy metabolism. The cells showed signs of oxidative stress, a chemical strain that can damage proteins, lipids, and DNA.

Motor neurons paid the highest price. These cells stretch long axons from the spinal cord to distant muscles, especially in the legs and feet. To maintain those long connections, they need a steady flow of energy. When that supply shrinks, they cannot keep up with repairs or signal traffic, and they gradually degenerate.

As motor neurons falter, muscles receive fewer signals and begin to shrink. Feet may curve or twist as balance is lost. A doctor examining a patient may see a positive Babinski sign, an abnormal reflex that points to nerve pathway damage. The chain from gene to energy failure to nerve injury becomes painfully clear.

The mutation sits in every cell, but tissues with lower energy demands can cope. Motor neurons cannot. Their dependence on a constant energy stream makes them the first to show the damage that MINA syndrome brings.

When the same NAMPT mutation was placed into mice, the animals did not show obvious movement problems in daily life. At first glance, it would have been easy to dismiss the variant as harmless. But when the research team looked closer at the animals’ nerve cells, they saw the same internal faults present 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.”

That gap between outward behavior in mice and subtle damage in nerves is a reminder for you that laboratory models always have limits. They are powerful tools, but they do not fully capture how a disease feels and unfolds in a human body.

By pairing the mouse work with detailed tests on patient cells, the researchers built a stronger case. The mutation in NAMPT is not only biochemically disruptive. It causes a real sensory and motor neuropathy, now recognized as MINA syndrome and described in the journal Science Advances.

Right now, there is no cure for MINA syndrome. Still, the research gives scientists a clear target: the broken energy pathway inside motor neurons. Because the disease centers on NAD+ production, one approach is to boost this molecule or shore up related metabolic routes.

In the lab, Ding’s team and others are testing compounds that increase NAD+ levels or support mitochondrial function in affected cells. If these treatments can restore energy balance in nerve tissue, they might slow or ease symptoms. Such strategies could also inform therapies for more common neurological conditions that involve energy failure.

For families living with unexplained muscle weakness and coordination loss, the recognition of MINA syndrome also has emotional weight. It offers a concrete explanation, a defined cause, and a path toward genetic testing. That clarity can help guide care and connect patients to research efforts across borders.

This work shows how a single change in an energy related gene can selectively damage motor neurons, even though the mutation sits in every cell in your body. That insight sharpens the way scientists think about nerve health. It underscores the idea that maintaining strong energy metabolism is central to keeping long axons alive.

In practical terms, the discovery gives doctors a new diagnosis to consider when a child or adult presents with progressive weakness, coordination problems, and foot deformities that do not match known diseases. Genetic testing for NAMPT mutations could shorten the long, frustrating search for answers.

For researchers, MINA syndrome provides a clear model of how disrupted NAD+ production harms nerve cells. Therapies that boost NAD+ or protect mitochondria, if successful here, might be adapted for other neurodegenerative diseases where energy failure plays a role.

The study also highlights the power of collaboration between basic science and clinical practice. Years of careful work on NAMPT in the lab made it possible to recognize a rare disorder in a real family. That chain, from molecular experiments to bedside insight, offers a path forward for many other unexplained conditions.

Over time, understanding MINA syndrome may help protect movement and independence for people whose nerves are slowly losing power, and it may guide new treatments that keep motor neurons energized and alive.

Research findings are available online in the journal Science Advances.

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