A new Yale study offers insight into the development of an effective treatment for idiopathic pulmonary fibrosis.
IPF is a lung disease that leads to scarring within the lungs and impairs one’s ability to breathe. Researchers at the School of Medicine found that IPF patients show improvement after receiving supplementary doses of thyroid hormone. This finding offers researchers the opportunity to develop new treatments for IPF, a disease that typically leads to death three to five years after diagnosis in almost 50 percent of patients. This study was published in the journal Nature Medicine on Dec. 4.
“We identified key molecular pathways after seeing irregularities in a molecule that is a regulator of thyroid hormone activation,” said Naftali Kaminski, corresponding author of the study and chief of pulmonary medicine at the Yale School of Medicine. “But we still have dots that need to be connected.”
In the study, researchers administered the thyroid hormone in both injection and aerosol forms to treat mice with IPF, comparing those results to mice that had IPF but did not receive the treatment. The mice that received the treatment showed a decrease in lung scarring, indicating amelioration of the disease. The study concluded that administration of the thyroid hormone improves the functioning and processing of mitochondria, which are small cell organs that regulate metabolism. The team’s results hold up to precedent since malfunctioning mitochondria have already been linked to the progression of IPF, according to Kaminski.
Both methods of administration proved effective in restoring the functioning of cells’ mitochondria, according to the study. However, the injections made the levels of the thyroid hormone in the blood dangerously high, which killed some of the mice, Kaminski said. He added that the aerosol administration did not increase hormone levels in the blood but helped reduce the fibrosis, making it the preferred method of treatment. The team hopes to eventually convert the aerosol treatment into a pill for humans to take.
The study is especially relevant considering that incidence of IPF has continued to rise in the U.S., Kaminski said.
“[IPF] was considered rare until 10 or 15 years ago. We don’t know exactly why that is, but IPF has the same risk factors as many other 21st-century diseases, like diabetes and heart disease.” Kaminski said. “Many of the patients who used to die from heart disease now live longer, so they have a higher risk of developing IPF.”
The current treatment options for patients do very little to improve the quality of life, said Guoying Yu, a co-author of the paper and a member of Kaminski’s lab. The two Food and Drug Administration-approved treatment options for IPF slow down the process and slightly extend lifespan but do not make patients feel or get better, Kaminski said. He added that he is optimistic that the thyroid hormone treatment would be a better alternative, as it both reduces symptoms and extends lifespan.
The other benefit to developing this treatment is that the thyroid hormone has already undergone testing and has a known safety profile with the FDA, which means that the drug approval process would be significantly shorter, Kaminski said. This is known as drug repurposing, or switching the application of known drugs to treatment of new diseases. According to the FDA, it can take up to 10 years for new drugs to be evaluated and approved, but this IPF treatment could be available in just a few years, Kaminski added.
Although this potential is promising, the researchers must still continue running trials and collecting data, Yu said. He added that researchers must conduct additional studies to determine appropriate dosage and mode of delivery while ensuring that the treatment is safe and effective for humans.
IPF affects between 132,000 and 200,000 people in the U.S., according to the Pulmonary Fibrosis Foundation.
Madison Mahoney | madison.mahoney@yale.edu