Antipsychotics treat brain virus

A type of drug used to treat schizophrenia can protect brain cells from a virus that causes a fatal nervous system disorder, say experts.
The disorder is called progressive multifocal leukoencephalopathy or PML.

It affects people with weakened immune systems, such as people with Aids or organ transplant patients.

A US study in Science found the antipsychotic drug clozapine appeared to be most effective at preventing the infection without side-effects.


This approach may offer hope for the treatment of one of the most unpleasant opportunistic illnesses of all
Keith Alcorn, National Aids Manual

PML is caused by a virus which destroys glial cells that produce the fatty sheath that covers nerve cells.
Most people carry the virus. But a healthy immune system suppresses it, and it only causes PML in people with weakened immune systems.

The symptoms of PML include dementia, vision loss, movement and speech impairment, paralysis and coma. The condition is always fatal.

The scientists found the virus attaches itself to a receptor on the surface of glial cells.

That receptor opens and allows the virus to get inside cells.

It normally binds with serotonin, a brain chemical that plays an important role in depression and anxiety, leading the scientists to investigate if medications which act as serotonin-receptor blockers could be effective.

Entry blocked

The team at Brown University and Case Western Reserve University focussed on a particular protein, called clathrin within the cells, which plays a role in bringing substances into the cell.

They then tested drugs to see which might be effective in blocking the action of this protein.

Chlorprozamine, a drug used to control psychotic symptoms such as hallucinations and delusions, was found to work.

But it can cause serious side effects, such as lowered blood pressure, stiffness and tremors.

This led the team to test seven similar drugs. They found that three others, most notably the antipsychotic clozapine, also prevented infection in human glial cells without the side effects.

The team say their research shows that the virus can be stopped in its tracks using clozapine and comparable serotonin receptor blocking drugs.

They suggest other drugs could have the same effect, and plan further studies.

Dr Walter Atwood, a virologist based at Brown University who worked on the study, said the drugs may prove to be an effective, ready-made therapy for PML prevention or treatment.

He added: "This is very promising. These are generic drugs we can take off the shelf that may help a lot of people."

'Difficult to treat'

Bryan Roth, professor of biochemistry at the Case School of Medicine, who also worked on the research, said: "It is likely that there are many other drugs with none of the potential side effects of antipsychotic drugs that will also block infection."

Keith Alcorn of the National Aids Manual, said: "This approach may offer hope for the treatment of one of the most unpleasant opportunistic illnesses of all."

He added: "PML is now rare in people with HIV but remains extremely difficult to treat in patients who succumb to it despite successful antiretroviral treatment."

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