An illustration of Guillain-Barré syndrome, which occurs when the immune system mistakenly attacks the fatty sleeves (orange) that surround nerves and the fibres extending from peripheral nerves (blue), located outside the brain and spinal cord

NEMES LASZLO/SCIENCE PHOTO LIBRARY

A treatment for Guillain-Barré syndrome has worked well in a late-stage clinical trial and may be approved next year. This would make it the first targeted treatment for the sudden and debilitating autoimmune condition.

“Patients got better sooner and more completely on every measure in our studies,” says Doug Love at Annexon Biosciences, the Californian company developing the treatment.

Guillain-Barré syndrome is a rare condition that can affect anyone who has recently had an infection, like food poisoning or influenza. After fighting the bacterium or virus causing the infection, a person’s immune system starts mistakenly attacking their nerves, for reasons that are poorly understood.

This assault causes weakness or tingling in the arms and legs, which can progress to difficulty walking, speaking, swallowing and breathing, and sometimes paralysis or death. “It’s one of the most striking diseases I’ve seen in 30 years working in biotech,” says Love. “It is completely sudden, it is completely indiscriminate – it can affect young, old, male, female, rich or poor – and it is immediately life-threatening,” he says.

The new treatment, called tanruprubart, is a monoclonal antibody that works by blocking a protein in the blood called C1q. This switches off a branch of the immune system called the classical complement pathway that is misdirected to attack nerves in Guillain-Barré syndrome. 

In a late-stage trial in Bangladesh and the Philippines, 241 people who had recently been diagnosed with the condition were given a single intravenous infusion of tanruprubart or a placebo infusion. On average, those treated with tanruprubart required 28 fewer days of mechanical ventilation to help them breathe and seven fewer days in intensive care, and were able to walk independently 31 days earlier. A higher proportion also reported feeling “very much improved” after one week.

People with the syndrome often take a long time to recover, but the participants who received tanruprubart experienced greater quality of life and mobility after two months compared with those who had the placebo. The results were presented at the Congress of the European Academy of Neurology in Geneva, Switzerland, in June.

No serious side effects occurred in the trial, and even though tanruprubart switched off part of the immune system, it didn’t appear to make the participants more vulnerable to infection. “Because it’s only a single infusion and you’re not chronically blocking the immune system, the risk of getting an infection is diminished,” says Love.

Based on these results, Annexon Biosciences recently submitted tanruprubart for approval from the European Medicines Agency. “It’s under review and we hope to get approval in the first part of next year,” says Love. The company will also submit it to the US Food and Drug Administration in the next few months, he says.

Guillain-Barré syndrome is most prevalent in low-income countries due to there being higher rates of infections that can trigger it, but it also occurs in high-income nations, including about 8000 cases in the US each year.

In rare cases, the condition can also be triggered by vaccines. This is because vaccines train the immune system to attack bacteria or viruses, which can sometimes lead to a mistaken immune attack on the nerves. However, infections are more likely to cause Guillain-Barré syndrome than the vaccines designed to prevent them.

Although tanruprubart was effective at treating Guillain-Barré syndrome in Bangladesh and the Philippines, it is unclear whether it will work as well in other countries, says Stefan Blum at the Princess Alexandra Hospital in Brisbane, Australia. This is because the condition tends to be triggered by different infectious agents depending on the location. “In developing countries, it’s often associated with gastrointestinal illnesses, like from [the bacterium] Campylobacter jejuni, whereas in developed countries it is much more associated with viral infections.”

Currently, Guillain-Barré syndrome is treated with plasma exchange or intravenous immunoglobulin, which help to calm the overactive immune system. However, because these treatments are non-targeted, they have limited efficacy. “They’re useful, but not fantastic,” says Blum. “It would be fantastic to have some new therapies for Guillain-Barré syndrome because there’s been absolutely nothing new on the market for 25 or 30 years now.”