Every year, approximately one in 50,000 children is born with Alport syndrome—a rare disease caused by gene mutations that lead to hearing defects, eye abnormalities and chronic kidney failure. By the time they are in their forties, their health will have worsened with most facing end-stage kidney failure, which can be fatal if they are unable to get a kidney transplant.

Now, new hope has come in the form of an antibody therapy developed by a team of scientists from Duke-NUS that preserves kidney function in these patients by blocking a cell signalling protein, interleukin-11 or IL11.

“IL11 had recently been implicated by other research in kidney scarring and dysfunction,” said Assistant Professor Anissa Widjaja from Duke-NUS’ Cardiovascular and Metabolic Disorders Programme. “We wanted to find out if it (IL11) played a role in Alport syndrome,” she added.

Using a preclinical model of Alport syndrome, Widjaja and her collaborators tracked IL11 levels during disease progression. Six weeks into the disease, the researchers found signs of kidney failure as the organ’s filtering sieve—the glomerulus—that separates blood from urine began to break down, causing blood cells to leak into the urine and waste products to accumulate in the body.

Around the same time, IL11 levels started to increase. Probing further, they looked at whether damage to the kidneys could be reduced by blocking IL11 with an antibody drug therapy, an anti-IL11, before the kidneys start to fail at this stage.

“We found that administration of anti-IL11 therapies, in the form of an antibody drug, has beneficial effects in reducing the severity of Alport syndrome in the preclinical model,” added Widjaja who collaborated with Professor Stuart Cook and Duke-NUS Dean nephrologist Professor Thomas Coffman on the study.

The findings could prove to be a gamechanger for Alport syndrome patients who are currently treated with angiotensin-converting enzyme inhibitors (ACEi) to reduce damage to the glomerulus by lowering the blood pressure in the kidneys. “ACEi are effective, but not in the long run,” said Widjaja. “Eventually, the kidneys will still fail.”

But with anti-IL11 therapy thrown into the mix, the team noticed something different. Instead of displaying the hallmarks of end-stage kidney failure, an improvement in kidney function was observed in the preclinical model that received the drug cocktail, increasing its lifespan. The team published their findings earlier this year in the Journal of the American Society of Nephrology.

“This is because anti-IL11 targets other symptoms of Alport syndrome like kidney inflammation and kidney scarring. So, if both drugs are taken together, it will be more effective as more symptoms are targeted at the same time,” explained Widjaja.

“This discovery spells new hope for treatment in Alport Syndrome—not just to arrest the progress of the disease, but even to restore lost kidney function. Also, the study suggests that anti-IL11 therapeutics can have additive effects with ACEi treatment, enhancing its potential utility in the clinical arena.”

Professor Thomas Coffman

With a promising treatment for Alport syndrome in the bag, Widjaja and her colleagues are far from finished. She said: “We are continuing our study to see if these therapeutics can be given not only as a preventative measure but also as treatment to reverse end-stage kidney failure.”