KL4 Surfactant Treats Lung Injury and Fibrosis Caused by Radiation in Early Study

KL4 Surfactant Treats Lung Injury and Fibrosis Caused by Radiation in Early Study

Windtree Therapeutics recently presented preclinical data supporting the potential effectiveness of its KL4 surfactant against acute and chronic lung injury and fibrosis induced by exposure to radiation.

The data were presented at the 62nd Radiation Research Society (RRS) Annual Meeting, that took place in Hawaii in October.

KL4 is a synthetic, peptide-containing surfactant structurally similar to the pulmonary surfactant in people. It contains the synthetic peptide KL4 (sinapultide), a 21-amino acid peptide that is designed to imitate the features of the human surface-active lipoprotein complex formed by type II alveolar cells in the lungs. These complexes are essential to reducing the surface tension of fluid in the lungs and keeping alveoli (the small air sacs) stable, preventing the lungs from collapsing with each expiration.

The KL4 surfactant is being developed to benefit individuals with lung injuries induced by radiation, like those caused by radiation therapy for lung and other thoracic cancers. It is also being developed for potential radiation exposure resulting from a nuclear accident or terrorist act.

Preclinical data presented at the RRS meeting, from a study conducted in mice, examined if the aerosolized KL4 surfactant could reduce acute and long-term lung injury related to radiation exposure. KL4 surfactant was administered into the animals’ lungs 24 hours after they had been exposed to high-dose thoracic-targeted X-ray irradiation (XRT).

The researchers looked for evidence of reduced blood oxygenation and signs of lung inflammation two to four weeks following exposure to XRT, as well as lung fibrosis, chronic pneumonitis, oxidative stress and local and systemic inflammation 18 weeks after XRT exposure. They assessed lung function, and analyzed bronchoalveolar fluid, serum and lung tissue.

Results showed that the surfactant preserved blood oxygenation, reduced lung inflammation, decreased lung fibrosis and pneumonitis, and reduced chronic radiation-induced lung injury.

“[A] Phase I SBIR grant of $600,000 from the … National Institutes of Health (NIH) provided us the opportunity to explore the use of KL4 surfactant to mitigate damage to lungs after radiation exposure,” Craig Fraser, president and chief executive officer of Windtree Therapeutics, said in a press release. “We are very encouraged by the results of this early preclinical work and are grateful for the support provided by the NIH.”

The company was recently given an additional $3 million “to support the further exploration of aerosolized KL4 surfactant as a potential medical countermeasure for radiation exposure,” Fraser added.

“Though an early study, these data are especially encouraging as the U.S. Department of Health and Human Services has indicated that there is an urgent and unmet need to develop medical countermeasures to prevent radiation pneumonopathy that can be efficiently administered within days, if not hours post-exposure.” said Robert Segal, MD, Senior Vice President, Clinical Development & Academic Affairs, Windtree Therapeutics.

“These data … represent progress toward potentially providing an effective and efficient means to counter exposure to potential radiation lung damage … including potentially as a result of cancer radiation therapy,” said Robert Segal, MD, senior vice president, Clinical Development & Academic Affairs, at Windtree.

KL4 surfactants may also be a potential therapeutic for lung diseases like pulmonary fibrosis.

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