Nimodipine Can Prevent Spasticity Following Spinal Cord Injury, Mouse Study Shows

Nimodipine Can Prevent Spasticity Following Spinal Cord Injury, Mouse Study Shows
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Nimodipine, an approved medication to prevent brain damage caused by hemorrhage, can be used to prevent spasticity following a spinal cord injury, a mouse study shows.

In addition to spinal cord injury, nimodipine may be a promising treatment for neurodegenerative disorders such as multiple sclerosis (MS) and amyotrophic lateral sclerosis, in which spasticity often develops, investigators noted.

Findings were reported in the study, “Early delivery and prolonged treatment with nimodipine prevents the development of spasticity after spinal cord injury in mice,” published in the journal Science Translational Medicine.

Spinal cord injury (SCI), a condition in which a portion of the spinal cord becomes damaged, often leads to permanent motor and sensory impairments that can affect different parts of the body, depending on the location of the injury.

Excessive tightness and involuntary muscle contractions, also known as spasticity, is one of the most frequent comorbidities of SCI. Indeed, statistics indicate that in the months following SCI, up to 70% of patients develop spasticity.

“Despite major progress in neurorehabilitative and pharmacological approaches, therapeutic strategies for treating spasticity are lacking,” researchers wrote.

Investigators at the University of Copenhagen, in Denmark, in collaboration with colleagues at the Karolinska Institutet, in Sweden, and the Central Institute of Mental Health, in Germany, discovered that nimodipine — a medication originally developed to treat high blood pressure — can prevent spasticity in a mouse model of SCI.

In their experiments, researchers showed that when they treated mice with nimodipine — administered by an under-the-skin injection at a dose of 10 mg/kg — for a period of six weeks, starting the day after the spinal cord lesion, animals did not develop spasticity or showed only mild signs of it for the following nine weeks.

However, if they started treating animals later — six weeks after the lesion, rather than on the following day — nimodipine was no longer effective at preventing the onset of spasticity.

“We show that nimodipine by and large can prevent the development of spasticity after a spinal cord injury if administered soon after the injury and for an extended period of time,” Ole Kiehn, professor in the department of neuroscience of the University of Copenhagen, and co-author of the study, said in a press release.

“One of the most surprising and interesting elements in the study is that the effect continues, even after treatment has stopped,” Kiehn said.

Carmelo Bellardita, co-author of the study, said: “We had guessed that the spasticity would be blocked for as long as the pharmacological treatment was ongoing. But we were positively surprised to see that the development of spasticity remained blocked even after we stopped the pharmacological treatment.”

Nimodipine works by blocking the activity of L-type calcium channels, a type of calcium channel found in nerve cells that potentially could be involved in the onset of spasticity following SCI.

In the study, investigators found that nimodipine blocks a particular subtype of these channels, called CaV1.3. They also showed that in genetically-modified animals whose neurons were unable to produce CaV1.3, spasticity failed to develop following SCI, mimicking the effects of nimodipine.

The team is now planning to investigate if nimodipine could have similar effects in humans.

“We are quite optimistic that nimodipine will have the same effect in humans. But we cannot be certain. Nimodipine is an approved drug that easily enters the brain, and we will now begin trials together with other researchers where we test nimodipine on healthy test subjects to study the effect on various reflexes and motor skills. Subsequently, it may potentially be possible to test the drug on people with spasticity,” Kiehn said.

Investigators also noted these findings are relevant not only in the context of SCI, but also for other neurodegenerative conditions in which spasticity often develops, as in MS.

“Because spasticity is commonly expressed in other neurological disorders like cerebral palsy, stroke, amyotrophic lateral sclerosis, and multiple sclerosis, the therapeutic action of the drug treatment may be of interest for several neurodegenerative pathologies [diseases],” the researchers wrote.

Joana holds a BSc in Biology, a MSc in Evolutionary and Developmental Biology and a PhD in Biomedical Sciences from Universidade de Lisboa, Portugal. Her work has been focused on the impact of non-canonical Wnt signaling in the collective behavior of endothelial cells — cells that made up the lining of blood vessels — found in the umbilical cord of newborns.
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Patrícia holds her PhD in Medical Microbiology and Infectious Diseases from the Leiden University Medical Center in Leiden, The Netherlands. She has studied Applied Biology at Universidade do Minho and was a postdoctoral research fellow at Instituto de Medicina Molecular in Lisbon, Portugal. Her work has been focused on molecular genetic traits of infectious agents such as viruses and parasites.
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Joana holds a BSc in Biology, a MSc in Evolutionary and Developmental Biology and a PhD in Biomedical Sciences from Universidade de Lisboa, Portugal. Her work has been focused on the impact of non-canonical Wnt signaling in the collective behavior of endothelial cells — cells that made up the lining of blood vessels — found in the umbilical cord of newborns.
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