Researchers from Northwestern University have discovered a compound with the ability to stop the progressive degeneration of motor neurons in those with amyotrophic lateral sclerosis (ALS). The continued breakdown of these neurons is a key driver of the neurodegenerative condition. This information is not only helpful for the development of ALS treatments, but for other rare diseases as well, such as primary lateral sclerosis and hereditary spastic paraplegia.
Amyotrophic lateral sclerosis (ALS) is a progressive, neurological disease in which nerve cells in the brain stem, brain, and spinal cord deteriorate. Due to this deterioration, muscles weaken and people lose control of them and their voluntary movement. In the late stages of ALS, the muscles necessary for breathing weaken, resulting in death. There are two forms of this disease: sporadic and familial. The former is the most common, with 90-95% of cases falling into this category. In the familial form of the disease, it is known that a mutated gene is inherited from parents, but it is still not fully understood and only accounts for 5-10% of cases. Otherwise, the cause of ALS is unknown. Researchers believe that there is a connection between frontotemporal dementia and ALS. Another theory is that exposure to certain substances or toxins leads to the development of ALS.
Symptoms of ALS vary between individuals. They also worsen as the disease progresses. Symptoms begin with difficulty with small movements and everyday things like walking. At the onset of the disease, people may trip and feel weakness in their arms, hands, and legs. As it progresses, people experience difficulties with speaking and swallowing, slowed and slurred speech, twitches and cramps in the muscles, and difficulty holding good posture. In the later stages people will be unable to move their muscles gradually, which affects the entire body. This inability affects movements like blinking. While people with ALS experience loss of muscle function, they do not lose any of their cognitive abilities.
About the New Compound
Titled NU-9, this compound was discovered by Hande Ozdinler and Richard B. Silverman, two professors from Northwestern University. Their study will be published in Clinical and Translational Medicine.
NU-9 is able to better the health of upper motor neurons by confronting two of the factors that lead to disease. These are proteins misfolding and clumping. In the majority of ALS patients, proteins fold incorrectly and build up within cells, becoming toxic and causing pathology, such as the TDP-43 protein pathology.
The researchers believed that their new compound would address the upper motor neurons that see misfolded proteins aggregate. When tested in mice, data suggested that they were correct. The research team noticed that the endoplasmic reticulum and mitochondria of the cells were becoming healthier, therefore improving the overall health of the motor neurons. In fact, the compound helped so much that disease neurons were comparable to healthy neurons after 60 days.
Ozdinler and Silverman plan to continue to evaluate these results in a Phase 1 trial of NU-9. They believe that this compound has the potential to help many with ALS and other neurodegenerative conditions.
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