Researchers have uncovered a molecular pathway that is altered during the onset of schizophrenia. They then used a cancer drug currently in advanced clinical trials to reduce symptoms of the illness in mice.
Investigators believe the finding may one day lead to new pharmacological approaches for schizophrenia.
The research, published online in the journal Brain, is from a group led by neurobiologist Peter Giese, Ph.D., at King’s College London.
Schizophrenia affects about 24 million people worldwide. The illness is a long-term condition that causes a number of psychological symptoms, including hallucinations and delusions as well as behavior changes.
The exact cause of the illness is unknown, although it is generally believed to be a combination of genetic and environmental factors. According to the World Health Organization, 90 percent of people with untreated schizophrenia are in developing countries.
Current treatments for schizophrenia include behavioral approaches such as psychotherapy, counseling or cognitive behavioral therapy and/or medication. However, many of the antipsychotic drugs or major tranquillizers used to treat or manage the illness have significant side effects.
“For the first time we have found that an enzyme activator called p35 is reduced in patients with schizophrenia and moreover; modeling this reduction in mice led to cognitive impairment typical for this disease,” Giese said.
“This gives us a better understanding of the changes that occur in the brain during the onset of schizophrenia.”
According to experts, a protein called Cdk5 is necessary for proper brain development. The creation of Cdk5 results, in part, by the presence of an enzyme in the brain, called p35.
In a study of human post-mortem brains, there was approximately 50 percent less p35 in the brains of patients who had suffered from schizophrenia.
These molecular changes were then modeled and monitored in mice that had been modified to contain a comparable reduction in the p35 enzyme.
As a result of this reduction in p35, the mice showed a reduction in synaptic proteins – important in maintaining neural connections – and displayed symptoms associated with schizophrenia, including learning impairments and inability to react to sensory stimuli.
Understanding this signalling pathway and the impact of low levels of p35 is important in finding potential future treatments for the disease.
“We noted that the reduction in p35 affects the same molecular changes targeted by a cancer drug called MS-275, so we administered this drug to the mice. We were excited to find that MS-275 not only addressed the molecular changes but also alleviated the symptoms associated with schizophrenia,” Giese said.
“Our findings encourage the future exploration of these types of drugs for treating impaired cognition in schizophrenia.”
Source: King’s College London