Little-known drug could help people with deadly and incurable condition

A little-known drug may offer hope for a currently incurable and deadly condition, with many patients dying within three years of diagnosis. Idiopathic Pulmonary Fibrosis (IPF) is a progressive and terminal disease that leads to lung scarring and increasing difficulty with breathing. It’s a serious and life-limiting illness affecting around 70,000 people in the UK annually, according to Action for Pulmonary Fibrosis. Amy Price, mother of Katie Price, was diagnosed with IPF in 2017 and continues to fight the disease.

Sadly, there is no cure and while treatments can help, they can only delay its progression. And whilst this is a disease of aging and is rarely seen before age 50, the experts say the findings also massive hope that this approach could work for other similar aging related diseases. However a current drug that is used for cancer could hold the key. According to the latest research by Tulane University, researchers at have identified a potential new way to treat IPF.

In a study published in the Journal of Clinical Investigation, researchers at Tulane University suggests that an FDA-approved cancer drug could assist the immune system in removing damaged cells responsible for lung scarring, potentially improving lung function in patients with IPF. The research highlights that in healthy lungs, fibroblasts, specialised cells, aid in tissue repair. However in individuals with IPF, some fibroblasts and nearby epithelial cells malfunction, becoming "senescent"—cells that neither divide nor die as they should. These dysfunctional cells accumulate, contributing to the development of stiff and scarred lung tissue.

The researchers discovered that senescent, or aging, cells accumulate when the immune system is unable to effectively eliminate them. This appears to be due to a protein called CTLA4, which acts like an emergency brake, dampening immune activity. To address this, scientists used the cancer drug ipilimumab in mice to block CTLA4. By lifting this immune "brake," they enabled T cells—key immune defenders—to clear out the aging fibroblast cells. As a result, the mice showed improved lung healing and reduced scarring.

“The CTLA4 protein normally functions to prevent excessive inflammation by blocking overactive T cells,” said senior author Dr. Victor Thannickal, professor and Harry B. Greenberg Chair of Medicine at Tulane University’s John W. Deming Department of Medicine. Too much of this ‘blocker protein’ may result in losing the ‘good’ inflammation that is needed to remove senescent cells. What we’re doing is blocking the blocker.”

The researchers focused on CTLA4 as a possible treatment target after finding high levels of it on T cells in the most scarred parts of lung tissue from humans and mice with IPF. Mice treated with ipilimumab healed their lungs better and recovered faster than those that didn’t get the drug.

“This opens up an entirely new direction for potential treatment of IPF,” said lead author Santu Yadav, PhD, assistant professor of medicine at the Tulane University School of Medicine. “Instead of using drugs to kill senescent cells, we are re-activating our own immune system to clear them out.”

More studies are needed to see how well drugs that target CTLA4 or other “checkpoint proteins” can help refresh the immune system. One major challenge is finding a safe dose that lets the immune system clear out aging cells without triggering too much inflammation.

“If it works in IPF, this immune rejuvenating approach to treatment may be effective in other diseases such as Alzheimer’s or cardiovascular diseases in which senescent cells are known to accumulate,” Thannickal said. “Can the right drug activate T cells in a way that clears senescent cells without causing collateral damage? If so, we may be closer to combating many aging related diseases and perhaps even aging itself.”

Common symptoms can include:

• Shortness of breath (breathlessness)
• Dry cough
• Tiredness (fatigue)
• Unexplained weight loss
• Clubbing of fingers and toes (swollen and rounded finger and toe tips)

Risk factors for pulmonary fibrosis can include:

• Ageing
• Family history (the genes inherited from your parents)
• Breathing in something that irritates the lungs, such as smoke or dust – this will usually happen repeatedly over a long time
• Some medications
• Other conditions, such as rheumatoid arthritis
• Gastro-oesophageal reflux disease (GORD)