Schizophrenia gene function offers hope for drug R&D

By Wai Lang Chu

- Last updated on GMT

An AstraZeneca collaboration has identified the location of a
schizophrenia gene that is set to offer hope for more effective
drugs. The gene appears to affect the production of myelin, the
material that insulates nerve fibres.

The discovery sets up a scenario that could lead to an enhanced treatment of schizophrenia - one of the most common psychiatric health disorders that affect an average of one per cent of the world population.

Today's methods of treatment can partially alleviate the symptoms but many patients are not helped at all by them. Normally patients become ill between the ages of 15-30 and remain so for the rest of their lives.

Researchers from Uppsala University and AstraZeneca had previously found the QKI gene is a possible contributing cause of the disease schizophrenia. Now they have found that QKI normally regulates the myelin genes.

In addition, the study revealed that the genetic expression of QKI is altered in schizophrenic patients and that the change correlates directly with the change in the myelin gene expression.

Resent research has suggested that approximately 70 per cent of patients will benefit from current treatments but there is conflicting evidence that suggests the chances of any one drug working for a person may be only 50 per cent so.

Second-generation antipsychotics (also called atypical antipsychotics) have shown more success with some patient population in treating negative and cognitive symptoms.

"In schizophrenics, fewer myelin proteins and less myelin are produced, we believe. Since myelin functions as an insulating substance around nerve fibres, impulse transmission is hampered in schizophrenics,"​ said Elena Jazin, research scientist at Uppsala University.

The team of scientists has also seen that a variant of QKI called 7kb is the variant that changes most in schizophrenic patients. This 7kb also has a major effect on the expression of myelin genes in these patients.

"Just how the reduction of myelin affects the symptoms in schizophrenic patients is something we must investigate further,"​ Jazin commented.

It is hoped that the new findings will lead to improved treatment of schizophrenia in the future.

"We hope that existing drugs can be altered so that more patients will be helped and the side effects reduced. Perhaps the findings will also lead to new medicines. But this will require research and will take a long time,"​ she added.

According to the American Psychiatric Association antipsychotic medications are indicated for nearly all acute psychotic episodes in patients with schizophrenia.

In addition to antipsychotic medications, some patients also take anti-depressants or mood-stabilizers to help control related symptoms.

The main issue though is that antipsychotic drugs are only thought to provide symptomatic relief from the postive symptoms of psychosis.

The newer atypical antipsychotic medications (such as clozapine, risperidone, olanzapine, quetiapine, ziprasidone and aripiprazole) are usually preferred over older typical antipsychotic medications (such as chlorpromazine and haloperidol) due to their favourable side-effect profile.

Bristol Myers Squibb's Abilify (Aripiprazole) is a drug from a new class of antipsychotic drugs (normally named 'dopamine system stabilisers' or 'partial dopamine agonists') that recently been developed and is now widely licensed to treat schizophrenia.

Related topics: Preclinical Research

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