Study Identifies New Molecular Treatment Candidate for IPF

Study Identifies New Molecular Treatment Candidate for IPF

Researchers have found that the activity of a protein, called heat shock protein 90 (Hsp90), is elevated in lung cells of patients with idiopathic pulmonary fibrosis (IPF). They also identified a molecule (17-AAG) that attenuated the activity of Hsp90 and prevented fibrosis in an IPF mouse model. The molecule could be a new IPF treatment candidate, researchers say.

Their work was published in the journal JCL insight, in an article titled “Hsp90 regulation of fibroblast activation in pulmonary fibrosis.”

In IPF, the lung tissue gets thick and scarred, and breathing becomes increasingly difficult. Fibroblasts are cells that produce collagen and other proteins in connective tissues, and play an important role in repairing tissue injuries. Studies for the past decade suggest that repeated activation of fibroblasts, by chronic injury,  are responsible for the formation of scar tissue in IPF, and researchers are seeking to identify the molecular cause of this activation.

With that intent, a research team at Cincinnati Children’s Hospital Medical Center used a publicly available gene expression database from IPF patients (lung biopsies), as well as other computational analyses, to enhance its understanding on the biological mechanisms behind IPF and search for new potential treatment targets.

They found that the activity of the protein Hsp90 was increased in fibroblasts of IPF patients.

“We investigated how fibroblasts become dysregulated, leading to their persistent activation and fibrosis,” Anil Goud Jegga, DVM and leader of the study, said in a press release. “We found that Hsp90 activity is elevated in fibroblasts isolated from fibrotic lesions and that it serves to activate the development of pulmonary fibrosis. By understanding this molecular mechanism, we were able to identify and test a potential treatment to reverse established and ongoing fibrotic lung disease,” he said.

Researchers identified several treatment candidates for IPF. One molecule in particular, called 17-AAG (17-N-allylamino-17-demethoxygeldanamycin), showed a potent weakening effect of Hsp90 activity.

When the team treated IPF mice with 17-AAG, they found that it significantly attenuated Hsp90-driven fibroblast activation, and prevented further fibrotic processes in the animals, suggesting that 17-AAG could be a new therapy candidate for IPF.

Because of the fibrosis-producing effects of Hsp90, this protein is of emerging research interest in different fibrosis areas, including the lungs, skin, heart and kidneys. In fact, a previous study also showed that blocking Hsp90 activity with 17-AAG attenuated fibrosis in the kidney and liver of a murine model. In addition, 17-AAG also has been found to control a number of proteins required for tumor growth and is currently being tested for cancer treatment.

“Our study also provides preclinical data to test safety and efficacy of 17-AAG or other Hsp90 inhibitors as potential treatment in patients with severe fibrotic lung disease,” said Satish K. Madala, PhD, co-leader of the study. “The small molecule Hsp90 inhibitors are currently in advanced clinical trials for various cancers. Hence, findings of this study can be relatively rapidly translated into clinical trials in patients with fibrotic diseases.”

One comment

  1. Randy Travis says:

    Interested in the 17-AAG . I’m 55 years old diagnosed IPF 2 years ago . I have lost my brother and my uncle to the disease .I have done stem cell therapy . My FVC is 44 percent.

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