Infantile spasm (IS) is a severe childhood epileptic syndrome and accounts for 50% of all cases of epilepsy that occur in children during the first year of life. Current treatment options for this disorder are limited, and most affected children grow up with developmental delays, intellectual disabilities, and other types of severe epilepsy.
An innovative study, conducted in the laboratory of Dr. John Swann, director of laboratories at the Gordon and Mary Cain Pediatric Neurology Research Foundation, researcher at Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital and professor at Baylor College of Medicinerevealed that the growth factor levels of insulin -1 (IGF-1) and its downstream signaling are reduced in the brains of both infantile spasm patients and animal models analyzed in the laboratory.
Not only, the team of experts revealed that administering an IGF-1 analogue to an animal model with infantile spasm successfully eliminated the spasms and abnormal brain activity. The extraordinary results of this research open new frontiers for the treatment of children diagnosed with infantile spasm.
The results of the study have been published in the scientific journal Annals of Neurology .
Infantile spasm: this is what the research says
Dr. Swann is one of the foremost experts in epilepsy research and, together with his team, has made discoveries that can be defined as pioneering in the field of severe epilepsy among subjects diagnosed with tuberous sclerosis.. Not only that, the distinguished scientist has developed a treatment for this pathology which has been approved by the FDA. In addition, Swann and his group of experts have long studied infantile spasm, an epileptic disorder diagnosed in approximately 2,500 children in the United States each year.
“It was previously reported that patients diagnosed with infantile spasm with pre-existing brain abnormalities have low levels of IGF-1 in their CSF and based on that study, we were interested in investigating whether IGF-1 levels were altered in the brains of animals. and patients with IS“Said Swann.
For their research, Swann’s team used an established method of inducing spontaneous epileptic spasms in rodents.. This methodology, developed in 2008 in Swann’s laboratory, involves chronic infusion of tetrodotoxin (TTX) into the cortex of the newborn rat brain, which causes lesions at the infusion site and causes spasms virtually identical to those seen in patients with infantile spasm.
“As expected after brain injury, we saw an increase in IGF-1 levels in non-neuronal support cells (also called glia) at the TTX infusion site. However, we were very intrigued by the noticeable and widespread decrease of IGF -1 expression in cortical neurons in brain regions adjacent to or further away from the TTX injection site, a phenomenon that had never been reported before “, Swann specified.
In a second step, Swann’s team of collaborators analyzed resected cortical tissue from patients with IS who had had previous perinatal strokes and had undergone surgery to control their intractable seizures. The results were remarkably similar to those they had seen in the IS animals.
“More importantly, we found that this reduction in cortical levels of IGF-1 had significant consequences in IS animal models because it dampened the overall activity of the molecular signaling pathways of IGF-1 that regulate many important biological processes involved in development. early brain and neuronal function “said Dr. Carlos Ballester-Rosado, a postdoctoral associate in Swann’s lab and first author of the study.
To determine whether increasing IGF-1 levels in the IS animal cortex could improve spasms, the team used a smaller version of IGF-1 that can cross the blood-brain barrier with greater ease than hormone a. full picture. The IGF-1 tripeptide they tested is a natural byproduct of IGF-1 breakdown that is normally found in the brain. Furthermore, this analog has previously been shown to successfully reverse behavioral defects in animal models of other neurodevelopmental disorders such as Rett syndrome and Phelan-McDermid syndrome.
“Using several lines of evidence, we first confirmed that this IGF-1 tripeptide was capable of activating the IGF-1 signaling cascade in mice.“, Explained Swann:”We then found – to our amazement – that IGF-1 administration successfully eliminated the spasms and an IS-specific chaotic brain activity pattern called hypsarrhythmia in most IS animals. We are thrilled because these findings raise the tantalizing possibility that this IGF-1 analogue may be used to treat patients with IS in the future. “
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