Novel flu treatment knocks out symptoms – in mice, anyway

November 3, 2003

Brussels, 31 Oct 2003

Scientists report they have treated the world's most deadly type of flu. If effective in humans, the treatment could halt the spread of future pandemics, such as SARS – at the very least it will put a stop to the dreaded winter aches and pains.

A research team from Imperial College London reported in this month's Journal of Experimental Medicine that they have developed a new strategy for treating the symptoms of the most virulent type of flu – influenza A – in animal tests.

This type of virus has been blamed for pandemics, such as the 1919 outbreak of 'Spanish flu', which killed over 20 million people worldwide. Unlike current attempts to prevent or treat influenza – yearly vaccinations which try to anticipate how the virus might mutate, or anti-viral drugs which must be given as soon as there is contact with the virus – this new treatment can be given after symptoms present themselves.

It is the immune system's over-reaction to flu which causes most of the damage. This exaggerated response during the onset of the virus produces inflammatory molecules which generate what is known as a 'cytokine storm'. Essentially, too many cells clog up the lungs and hamper oxygen transferring into the bloodstream. By selectively reducing this cellular overload, the team proved it is possible to eliminate clinical symptoms whilst effectively tackling and clearing the infection.

"Three times in recent history the flu virus has evolved from a disease characterised by coughs and sneezes into a world killer," said Dr Tracy Hussell of Imperial's Centre for Molecular Microbiology and Infection and senior author of the paper. The recent SARS epidemic highlights how quickly a deadly virus can spread and we are long overdue for the next flu pandemic, she warned. "The sobering reality is that influenza is one of the grand masters at evading human immune response."

Flu invaders

The body has two major classes of white blood cells, T and B lymphocytes. While B cells produce tailor-made antibodies which help the body remember and quickly respond to invaders, T cells patrol the body, seek out and destroy diseased cells. But the T cell response also produces inflammatory mediators which cause the 'storm'.

Until now, treatments to tackle this problem focused on inhibiting all T cells. But this leaves the patient unable to clear the virus and susceptible to other infections. Hussell's team developed a way of "down regulating" a molecule known as OX40 that only targets T cells which have recently been alerted to the presence of the flu virus.

Results show that, six days after infection with flu, mice immediately treated with a fusion protein called OX40:Ig were indistinguishable from uninfected control mice. But untreated mice lost 25% of their body weight, appeared hunched and lost their appetite – classic flu symptoms. The treatment also reversed these symptoms in mice several days after being infected. What's more, re-infected mice were found to be unaffected by the reduced T cell immunity brought on by the initial infection.

This remedy has scope in any disease characterised by an excessive T cell inflammatory response, whether in the lungs, such as bronchitis and asthma, or rheumatoid arthritis in the joints, said Hussell. "If the clinical symptoms of SARS are caused by an excessive immune response, it too could be effectively treated," she concludes.

DG Research
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