Scientists have identified a new compound that reverses damage to ALS neurons

Scientists at Northwestern University have identified the first compound that eliminates the continuous degeneration of upper motor neurons that become ill and are a key factor in ALS (amyotrophic lateral sclerosis), a rapid and fatal neurodegenerative disease that paralyzes its victims.

In addition to ALS, upper motor neuron degeneration results in other motor neurone diseases, such as hereditary spastic paraplegia (HSP) and primary lateral sclerosis (PLS).

In ALS, nerve cells in the brain that drive movement (upper motor neurons) and nerve cells that control the muscles in the spinal cord (lower motor neurons) die. The disease results in rapidly progressing paralysis and death.

To date, there has been no drug or treatment for the cerebral component of ALS, nor a drug for patients with HSP and PLS.

“Although upper motor neurons are responsible for triggering and modulating movement, and their degeneration is an early event in ALS, so far there has been no treatment option to improve their health,” said senior author Hande Ozdinler, an associate professor of neurology at the School of Medicine. University of Northwestern Feinberg. “We have identified the first compound that improves the health of upper motor neurons that become diseased.”

The study will be published in Clinical and translational medicine February 23.

Ozdinler collaborated with study author Richard B. Silverman and Patrick G. Ryan / Aon, a professor of chemistry in the Northwest.

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

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

The research team began researching whether NU-9 will be able to help repair upper motor neurons that become ill due to increased protein misalignment in ALS. The results on the mice were positive. The scientists then performed experiments to find out how and why the diseased upper motor neurons regained their health.

The new compound restores neurons to good health

After administration of NU-9, both the mitochondria (cellular energy producer) and the endoplasmic reticulum (cellular protein producer) began to regain their health and integrity resulting in improved neuronal health.

The upper motor neurons were more intact, their cellular bodies were larger, and the dendrites were not filled with holes. They stopped degenerating so much that diseased neurons became similar to healthy control neurons after 60 days of NU-9 treatment.

The main commanders of the movement

Improving the health of brain neurons is important for ALS and other motor neurone diseases. “

Hande Ozdinler, Senior Study Author and Associate Professor of Neurology, Northwestern University School of Medicine, Feinberg

The upper motor neurons of the brain are the main commanders of movement. They carry the brain that enters the targets of the spinal cord in order to initiate voluntary movement. Degeneration of these neurons disrupts the connection from the brain to the spinal cord and leads to paralysis in the patient.

The lower motor neurons have direct connections with the muscle, contracting the muscle to perform the movement. Therefore, the activity of the lower motor neuron is partially controlled by the upper motor neurons.

Ozdinler and colleagues will now complete more detailed toxicological and pharmacokinetic studies before launching a phase 1 clinical trial.

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