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Northwestern Scientists Repair and Reverse ALS Neuron Damage in Lab Using New Non-Toxic Compound


In a study that used a non-toxic substance in mice, Northwestern University researchers identified the first compound that eliminates the ongoing degeneration of brain neurons in the crippling disease known as ALS.

Researchers Hande Ozdinler and Richard Silverman -Northwestern

Amyotrophic lateral sclerosis is a neurodegenerative disease in which upper motor neurons are degraded in victims, leading to rapid and fatal death.

In addition to ALS, other motor neuron diseases, such as hereditary spastic paraplegia (HSP) and primary lateral sclerosis (PLS) progress in a similar way.

In ALS, the nerve cells that initiate movement in the brain (upper motor neurons) and the nerve cells that control the muscles in the spinal cord (lower motor neurons) die and, until now, there has been no drug or treatment to the brain component of ALS and no drugs for patients with HSP and PLS.

“Although upper motor neurons are responsible for the initiation and modulation of movement, and their degeneration is an early event in ALS, until now there has not been a treatment option to improve their health,” said lead author Hande Ozdinler, associate professor. of neurology at Northwestern University Feinberg School of Medicine.

“We have identified the first compound that improves the health of diseased upper motor neurons.”

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Ozdinler collaborated with study author Richard B. Silverman, a Northwestern professor of chemistry, and published the results in Clinical and Translational Medicine last month on February 23.

The study began after Silverman identified a compound, NU-9, developed in his laboratory for its ability to reduce protein misfolding in critical cell lines. The compound is non-toxic and crosses the blood-brain barrier.

“I’m very excited to find out if our hypothesis that upper motor neuron stabilization in mice will translate to humans and NU-9 will bring hope to those with currently untreatable upper motor neuron diseases,” said Silverman.

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Compound NU-9 addresses two of the important factors that make upper motor neurons sick in ALS: protein misfolding and protein buildup within the cell. Proteins fold in a unique way to function; when they fold badly, they become toxic to the neuron. Sometimes proteins aggregate within the cell and cause pathology as in the TDP-43 protein pathology. This occurs in about 90% of all the brains of ALS patients and is one of the most common problems in neurodegeneration.

The research team began investigating whether NU-9 could help repair upper motor neurons that become diseased due to increased protein misfolding in ALS. The results in mice were positive. Next, the scientists conducted experiments to reveal how and why diseased upper motor neurons regained their health.

Restore neurons for solid health

After NU-9 was administered, both the mitochondria (the cell’s energy producer) and the endoplasmic reticulum (the cell’s protein producer) began to regain their health and integrity, resulting in better neuron health . The upper motor neurons were more intact, their cell bodies were larger, and the dendrites were not riddled with holes.

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They stopped degenerating so much that diseased neurons became similar to healthy control neurons after 60 days of NU-9 treatment.

Movement Chief Commanders

Upper motor neurons are the commanders-in-chief of brain movement. They carry information from the brain to targets in the spinal cord to initiate voluntary movement. The degeneration of these neurons affects the connection of the brain to the spinal cord and leads to paralysis in patients.

The lower motor neurons have direct connections to the muscle, contracting the muscle to execute movement. Therefore, the activity of the lower motor neuron is controlled in part by the upper motor neurons.

Ozdinler and his colleagues will now complete more detailed toxicology and pharmacokinetic studies before starting a phase 1 clinical trial.

(Source: Northwest News Now)

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