Scientists at Northwestern University have found that the upper motor neurons are the main cause of ALS (Amyotrophic Lateral Sclerosis), a rapid and deadly neurodegenerative disease that causes illness and paralyzes victims. We have identified the first compound to eliminate denaturation.
In addition to ALS, upper motor neuron degeneration also causes other motor neuron diseases such as hereditary spastic paralysis (HSP) and primary lateral sclerosis (PLS).
In ALS, motor neurons in the brain (upper motor neurons) and muscle control neurons in the spinal cord (lower motor neurons) die. The disease results in rapidly progressing paralysis and death.
So far, there are no drugs or treatments for the brain components of ALS, and no drugs for HSP and PLS patients.
“Upper motor neurons are involved in the initiation and regulation of movement, and their degeneration is an early event of ALS, but so far there have been no therapeutic options to improve health,” said senior author Hande. Associate Professor Osdinler said. Neurology at Northwestern University School of Medicine Feinberg. “We have identified the first compounds to improve the health of diseased upper motor neurons.”
The study will be published at Clinical and translation medicine February 23.
Osdinler collaborated with research author Richard B. Silberman and Professor Patrick G. Ryan / Aon of Chemistry at Northwestern University.
The study was initiated after Silberman identified compound NU-9, which was developed in his laboratory for its ability to reduce protein misfolding in critical cell lines. This compound is non-toxic and crosses the blood-brain barrier.
NU-9 compounds address two key factors that cause upper motor neurons to become ill in ALS: protein misfolding and protein aggregation in cells. Proteins work by folding in a unique way. When they are accidentally folded, they become toxic to neurons. Like the pathology of TDP-43 protein, proteins can aggregate inside cells to cause pathology. It occurs in about 90% of the brains of all ALS patients and is one of the most common problems with neurodegeneration.
The researchers began investigating whether NU-9 could help repair diseased upper motor neurons due to increased misfolding of ALS proteins. The result in mice was positive. Scientists then conducted experiments to find out how and why the diseased upper motor neurons regained health.
New compounds restore neurons to robust health
After administration of NU-9, both mitochondria (cell energy producers) and endoplasmic reticulum (cell protein producers) began to regain health and integrity, improving neuronal health.
The upper motor neurons were more intact, their cell bodies were larger, and the dendrites were not full of holes. The diseased neurons resembled healthy control neurons 60 days after NU-9 treatment, as they stopped degenerating so much.
Improving the health of brain neurons is important for ALS and other motor neuron diseases. “
Hande Ozdinler, Principal Investigator and Associate Professor of Neurology, Northwestern University School of Medicine Feinberg
Upper motor neurons are the commander-in-chief of the brain. They carry the brain’s input to the spinal cord target to initiate spontaneous movements. Degeneration of these neurons impairs the connection from the brain to the spinal cord, causing paralysis in the patient.
Lower motor neurons are directly connected to muscles and contract muscles to perform exercise. Therefore, the activity of lower motor neurons is partially controlled by upper motor neurons.
Ozdinler and colleagues plan to complete more detailed toxicology and pharmacokinetic studies before starting Phase 1 clinical trials.
Scientists identify new compounds that reverse damage to ALS neurons
Source link Scientists identify new compounds that reverse damage to ALS neurons