Patients with IPF may benefit from pressure-treated yeast fiber compounds

Inhalable therapy is being developed using pressure-treated yeast beta-glucan for people with COVID-19 as well as other serious lung diseases, including idiopathic pulmonary fibrosis (IPF). Beta-glucans are fiber compounds that are found naturally in the cell walls of grains, bacteria, and fungi, such as yeast.

Ceapro, a biotechnology company based in Alberta, Canada, uses its patented Pressurized Gas eXpanded (PGX) technology to transform beta-glucans into highly soluble dry microparticles or free flowing powders with adjustable particle sizes.

Ceapro began collaborating with researchers at McMaster University in Canada in 2019 to use PGX-treated beta-glucans (PGX-YBG) to develop inhalable delivery systems to optimize therapy formulations for treat chronic illnesses, such as IPF. PGX-YBG particles have unique aerodynamic properties that allow them to be inhaled deep into the lungs, where tissue scarring (fibrosis) occurs.

Preliminary experiments with PGX-YBG alone or in combination with a drug, however, showed that PGX-YBG was able to modulate immune responses and function as an active component in anti-fibrosis treatment, rather than simply serving as a carrier. .

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“We have shown that PGX technology can convert materials that cannot be easily inhaled, in particular a YBG-based particle that has inherent immunomodulatory properties, into materials that can easily access the lung”, Todd Hoare, PhD, from McMaster’s chemical engineering department, said in a press release.

“By combining this property with the very large internal surface area of ​​the PGX-treated microparticles which enables high concentration drug loading using Ceapro’s supercritical drug impregnation process, we are very excited about the potential of this technology to treatment of lung disease, ”he said. added.

In IPF, excessive scar tissue formation leads to stiffening and hardening of lung tissue, making it difficult for patients to breathe. Recent studies have shown that pulmonary fibrosis can also occur and persist for months in some COVID-19 patients.

Evidence suggests that certain immune cells known as M2-type macrophages remain in fibrous lungs and release cell signaling molecules that stimulate other cells to constantly generate and deposit scar tissue.

Further experiments indicated that PGX-YBG selectively binds to a protein receptor, Dectin-1, found on the surface of macrophages. This binding event reprograms M2-type cells into M1-type macrophages which no longer release pro-fibrotic signaling molecules, initiating the removal of excess tissue.

” We showed, in vitro, that PGX-YBGs have the ability to prevent the activation of macrophages to a pro-fibrotic [behavior]. In addition, treatment with PGX-YBG of macrophages that have already acquired a pro-fibrotic effect [behavior] results in the reprogramming of macrophages to a [behavior] not known to be pro-fibrotic, ”said Kjetil Ask, PhD, pulmonary fibrosis expert at McMaster.

“Using cells from animals lacking the Dectin-1 beta-glucan receptor, we have shown that it is dependent on the presence of the Dectin-1 receptor,” Ask added. “These results are very exciting because reprogramming of macrophages is considered a viable therapeutic strategy against fibrotic disease and PGX-YBG appears to have this ability.”

PGX-YBG has also been shown to be safe when administered to mice, and preliminary data suggests that it was able to stop pro-fibrotic processes in an experimental animal model of pulmonary fibrosis. According to Ask, the team is now working to validate these results.

In anticipation of potential human trials, Ceapro scientists are working to optimize the delivery of PGX-YBG to the lungs and further validate the ability of PGX-YBG to reduce pulmonary fibrosis, both alone and when loaded with anti-inflammatory therapies.

“We are very satisfied with the progress made in this research project… [and] we believe that it certainly becomes necessary to conduct additional animal studies before undertaking human trials to develop the best possible tool in the fight against pulmonary fibrotic diseases, ”said Gilles Gagnon, President and CEO of Ceapro .

“We are grateful for the collaborative work with the McMaster University team and look forward to further development,” Gagnon added.

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