New study finds potential treatment target of SMA

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New study finds potential treatment target of SMA

Postby biokit » Nov 03 2016 8:34 am

Scientists have found for the first time through recombinant human proteins that mitochondria of nerve cells or motoneurons that affect muscle movement in the spinal muscular atrophy (SMA) are defective and mitochondria are the organelles that supply cells with energy. Damage of mitochondrial structure and function in motoneurons happens before the onset of symptoms, suggesting that they may play a role in disease progression. The findings, published in the journal Human Molecular Genetics, point to new possibilities for targeted therapies for SMA.

"Recovery of mitochondrial function may be a novel SMA treatment strategy," said Dr. Yongchao Ma, a senior author of the study. Dr. Ma is an MD, Ph.D., at the Stanley Muller Institute for Childhood Research at the Robert H. Lurie Children's Hospital in Chicago. He is also a Ph.D. research fellow at the American College of Pediatrics and Neurology at Northwestern University and assistant professor of physiology.

Infants who are born with SMA can't support their head or sit on their own, and they rarely survive 2 years of age. "Although the genetic causes of this devastating disease have been identified, our study describes how mitochondrial dysfunction may promote motor neuronal disruption even before the onset of symptoms," Dr. Ma said. "Our findings provide new insights into the pathogenesis of SMA, which are critical to the development of new therapies."

In analyzing the gene expression profiles of motoneurons from SMA and control mice, Dr. Ma and colleagues first discovered that mitochondria are associated with SMA. They observed that genes associated with many mitochondrial functions were significantly dysregulated in SMA motor neurons.

Using sophisticated techniques, the study found that in SMA motor neurons, mitochondria produce energy at a slower rate, depleting nerve energy. SMA mitochondrial membrane potential decreased, which proved that it is not so "healthy". It also has elevated levels of oxidative stress, which are toxic to neurons. Mitochondrial movement is also damaged, leading its joints in the nerve and muscle movement to be blocked, leaking toxins and eventually disrupting the neuromuscular junction. Mitochondria in SMA motor neurons are also broken and swollen, which is consistent with the mitochondrial functional defects measured in this study. "Motor neurons have higher energy requirements, which makes them very susceptible to defects in their own mitochondria," Dr. Ma said. "These defects may lead to the degeneration of motor neurons in SMA."
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