Pliant’s PLN-101325 Improves Muscle Function in Preclinical Models
Pliant Therapeutics said it plans to ask the U.S. Food and Drug Administration (FDA) for permission to begin clinical testing of PLN-101325, its experimental therapy for muscular dystrophy, by the end of this year.
In preclinical studies involving cell and animal models — the results of which were presented at a conference this week — treatment with PLN-101325 led to higher body weight, better recovery after muscle injury, and increased diaphragm strength in mice with muscular dystrophy-like disease.
Moreover, in human muscle cells affected by Duchenne muscular dystrophy, PLN-101325 was found to substantially improve muscle fiber organization, data showed.
Scott Turner, PhD, senior vice president and head of research at Pliant, presented the new preclinical data at the New Directions in Biology and Disease of Skeletal Muscle Conference, being held June 20–23 in Fort Lauderdale, Florida. Turner’s talk was titled “Increased Laminin Binding Through α7β1 Integrin Activation Protects Dystrophic Muscle.”
PLN-101325 is an antibody-based therapy designed to activate a protein receptor called integrin alpha seven beta one (a7B1). This protein is expressed on muscle cells, and it participates in signaling cascades that help to stabilize muscle fibers — implying that increasing its activity may help improve muscle strength and prevent muscle damage.
Levels of a7B1 are increased in people with Duchenne, the most common type of muscular dystrophy.
“Our novel approach of employing an allosteric activating antibody to increase laminin adhesion of muscle cells, could reduce the ongoing muscle injury and potentially enhance regeneration in muscular dystrophy patients,” Turner said in a press release.
Pliant said it “anticipated entry into the clinic in early 2023” to begin testing PLN-101325.
Prior research done in MD mouse models has shown that mice lacking integrin a7B1 have more severe disease. Conversely, increasing the expression of this protein leads to milder disease symptoms.
Mutations in the gene that codes for integrin a7B1 cause a form of congenital muscular dystrophy, the researcher noted.
At the conference, Turner shared data from tests of PLN-101325 in cell and animal models. Experiments in human muscle cells affected by Duchenne showed that treatment with the experimental antibody markedly improved muscle fiber organization, leading the cells to be more resistant to high-frequency stimulation.
In other experiments, PLN-101325 was used to treat mice with muscular dystrophy-like disease. Results showed that, compared with control mice, animals given PLN-101325 had greater body weight and better recovery after muscle injury. The treated mice also had the ability to exert more force with their diaphragm, the muscle used to pull air into the lungs while breathing.
“The increased diaphragm strength and function seen in [muscular dystrophy] mice treated with PLN-101325 highlight the potential of this novel therapy to treat a leading cause of death in muscular dystrophy patients,” Turner said.
Collectively, these results support PLN-101325 as a potential therapy for muscular dystrophy, according to Pliant.
The company said its therapy may be useful in combination with current standard treatments, and may be particularly helpful for older individuals who aren’t good candidates for new treatments like gene therapy.