Inflammation may be playing a role in the development of epilepsy in Tuberous Sclerosis Complex (TSC) patients, suggested Dr. Michael Wong and his laboratory.
Tuberous Sclerosis Complex (TSC), a multi-system disease, greatly impacts patients and their families due to the central nervous system manifestations. It leads to benign tumor growth in several organs, such as the brain, kidneys, heart, eyes, skin, and lungs, as well as central nervous system manifestations, such as epilepsy, autism, and cognitive impairment. According to the National Institute of Neurological Disorders and Stroke, most people with TSC will have seizures at some point in their lives. There is evidence to support a role for mTORC1 signaling in the neurological symptoms associated with TSC, and mTOR inhibitors are being tested as potential treatments.
‘Anti-inflammatory treatment could be a potential therapy for epilepsy in Tuberous Sclerosis Complex (TSC) patients.’
However, understanding the mechanisms involved downstream of mTORC1 is
important for identifying more specific therapeutic targets to minimize
the side effects observed with mTOR inhibition. Dr. Michael Wong and his
laboratory have posited that inflammation may be playing a role in the
development of epilepsy in TSC patients. Several studies have found that proteins indicative of inflammation are present in brain tissue from TSC patients. However, there are still many questions as to the inflammatory mechanisms involved, including the role of mTORC1 signaling.
With an Exploration - Hypothesis Development Award, Dr. Wong and colleagues screened for markers of inflammation in a mouse model of TSC that develops seizures around three to four weeks of age. They found the mRNA levels of several inflammatory molecules to be different from control mice at four weeks of age.
When the researchers checked at two weeks of age, they found mRNA levels were different at this earlier time point for three of the molecules, CCL2, IL-1beta, and CXCL10.
This suggests that the increase in CCL2, IL-1beta, and CXCL10 precedes seizures, but the difference in expression of the other molecules at four weeks of age may have been due to seizure activity. The Wong lab further demonstrated that protein levels of IL-1beta and CXCL10 were increased in the brain tissue of the TSC mice.
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Since rapamycin has been previously studied in epilepsy, Dr. Wong focused on ECG treatment in the mice and found that treatment did minimally correct some of the brain tissue abnormalities seen in the mouse model, but, more importantly, there was a small decrease in seizure development and slightly improved survival in these mice.
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Source-Eurekalert