Researchers find first gene target for brain motor neurons
Neuroscientists at Northwestern Medicine have discovered that treating amyotrophic lateral sclerosis (ALS) involves targeting the brain. This contradicts long-held beliefs that the disease begins in the spinal motor neurons and that any therapy must target the spine.
The latest Northwestern study indicates that brain motor neuron degeneration is not only a consequence of spinal motor neuron degeneration.
“We have discovered that the brain degenerates early in diseases like ALS, sends us warning signals and shows defects very early in the disease,” says Hande Ozdinler, lead study author.
“Therefore, we need to repair the brain motor neurons if we want long-term and effective treatment strategies. The brain is important in ALS.”
ALS is a rapidly progressing and fatal neurological disease that leaves patients paralyzed.
As many as 250,000 persons in the United States are affected each year by upper motor neuron diseases, such as ALS, hereditary spastic paraplegia, and primary lateral sclerosis. In the absence of a cure, there is no viable long-term treatment.
For the first time, a study has shown that brain motor neuron degeneration is not a result of spinal motor neuron degeneration, but rather is a separate condition.
Additionally, the research is the first to demonstrate that the gene UCHL1 is required for the health of brain motor neurons that are sick due to two distinct underlying reasons. The first is the buildup of incorrectly folded proteins, whereas the second is the accumulation of sticky protein clumps within cells. These complications are present in more than 90% of cases with ALS and other upper motor neuron diseases.
“Our findings not only give legitimacy for targeting brain motor neuron health in ALS as a therapeutic intervention, it also reveals the first target gene that can help these neurons be revitalized,” says Ozdinler.
“This has huge clinical implications,” adds Ozdinler.
“Being able to modulate gene expression in diseased brain motor neurons in upper motor neuron disease patients is mind boggling. Since movement starts in the brain, if we can make the brain motor neurons happy and healthy, if we can boost their health and integrity with directed gene delivery, we may begin to develop personalized treatment options especially for patients with upper motor neuron disease, who currently have no effective treatment options.”
NU-9, a compound discovered by researchers at Northwestern University, is the first to stop the degeneration of upper motor neurons, which is a major contributor to ALS. It has now been shown that treating the upper motor neurons in ALS is of critical importance as well as the primary genetic target.
The next step is to test the drug in at least two distinct ALS disease models to see if it improves movement and reduces disease symptoms. After conducting preclinical toxicological tests, scientists will move on to conduct clinical trials, a procedure that will likely take several years.
Source: Gene Therapy
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