KM-391, an experimental drug being developed by Cellceutix Corporation, has shown promise in autism treatment, the company announced.
KM 391 is a small molecule that is being developed to treat autism.
Preliminary testing of KM 391 in mice revealed that the test animals showed a significant increase in serotonin uptake compared to controls, with no apparent side-effects in the long-term administration of KM 391 in mice.
The equalization of serotonin uptake is considered by many researchers as an important development in the treatment of autism spectrum disorders.
Neonatal serotonin depletion and increased plasticity of the brain are salient features observed in autism.
To experimentally induce these changes, 5,7-dihydroxytyptamine (5,7-DHT) was injected into the forebrain bundle on the day of birth of Wistar rat pups. Litter mates were injected with saline with progeny matched mice serving as controls.
5,7-DHT treated control rats significantly reduced their exploration in response to spatial rearrangement and object novelty, suggesting increased anxiety in response to change.
A decrease in brain plasticity was observed, as well as a significant decrease in serotonergic (5-HT) innervation in the cortex and hippocampus; however, not in the subcortical forebrain.
These changes and abnormalities are similar to our understanding of brain disorders presenting with cortical morphogenetic abnormalities and altered serotonin neurotransmission, as in Autism.
For the study, 100 µl of 5,7-DHT were injected 4 hours after birth. The animals were observed hourly for a few days until survival was established.
Pair matching was done taking into consideration litter mating. Each group consisted of 10 male and 10 female rats with pair matching.
KM-391 was given orally at 2.5 or 5 mg/kg; for comparison, fluoxetine was given at 5 mg/kg; and the 4th group served as 5,7-DHT-treated controls.
The compounds were administered orally up to 90 days. The animals were scored for behaviorial patterns, plasticity and serotonin levels.
Behavioral scoring was done by standard behavioral test scoring, plasticity was calculated by surgical scoring, and serotonin levels were obtained by immunohistochemistry.
“Research on autism has been difficult because there has been no reliable animal model,” stated Dr. Krishna Menon, chief scientific officer of Cellceutix.
Autism is a behavior disorder, characterized by an impairment in social communication, social interaction, and social imagination.
Those with autism often have a restricted range of interests and display repetitive behaviors and mannerisms, along with altered reactions to the everyday environment.
1 percent of the population of children in the U.S. ages 3-17 have an autism spectrum disorder. Prevalence is estimated at 1 in 110 births.
More children will be diagnosed with autism this year than with AIDS, diabetes & cancer combined, studies suggest.
About 1 to 1.5 million Americans live with an autism spectrum disorder. 1 percent of the adult population of the United Kingdom have an autism spectrum disorder.
Cellceutix Corporation is a preclinical cancer and anti-inflammatory drug developer.
Cellceutix owns the rights to eight drug compounds, including Kevetrin, which it is developing as a treatment for certain cancers, and KM-391, which it is developing for the treatment of autism.