PhaseBio Announces Positive Data For Duchenne Muscular Dystrophy therapy in Pre-Clinical Mice Models

Margarida Azevedo, MSc avatar

by Margarida Azevedo, MSc |

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PhaseBio Pharmaceuticals, Inc., a clinical-stage biopharmaceutical company that develops novel drugs to treat diabetes and cardiovascular dysfunction in patients suffering from rare diseases, recently announced positive data from a pre-clinical study for the use of PB-1046 in Duchenne Muscular Dystrophy (DMD) mice models. The results were presented in a poster session this week during the 67th Annual Meeting of the American Academy of Neurology (AAN) that took place at the Walter E. Washington Convention Center in Washington, DC.

PB1046 is based on Vasoactive Intestinal Peptide (VIP), a naturally occurring neuropeptide that activates G protein-coupled receptors – VPAC1 and VPAC2 that are widely distributed throughout the cardiovascular, pulmonary and immune systems.

The poster “Chronic treatment with PB1046, a stable and long-acting vasoactive intestinal peptide receptor agonist, improves cardiac and skeletal muscle function in mouse models of Duchenne Muscular Dystrophy” reports the results of a study conducted by the Columbus-based QTest Labs in partnership with Ohio State College of Veterinary Medicine and the Nationwide Children’s Hospital.

Results from the study conducted in pre-clinical models of MDX, dystrophin-deficient mice, revealed that treatment with PB1046 improved DMD myopathies, decelerated cardiac deterioration, and by reducing fibrosis, PB1046 protected skeletal muscle.

“Patients with DMD are living longer primarily due to improvements in pulmonary support and as a result these patients are ultimately dying of heart failure. Current heart failure therapies have not been shown to normalize cardiac function in these patients. These data generated with chronic administration of PB1046 show the drug may be effective at slowing cardiac deterioration and protecting against contraction-induced damage, which could provide a valuable new therapeutic avenue for DMD and Becker muscular dystrophy,” said Pradeep Mammen, M.D., FACC, FAHA, Medical Director of the Neuromuscular Cardiomyopathy Clinic and Director of Translational Research for the Advanced Heart Failure Program at the University of Texas Southwestern Medical Center in a recent news release.

Specifically, findings from the study revealed that chronic administration of PB1046 was able to decelerate cardiac deterioration in MDX mice models, and provide important insights for clinical development strategies. During the study, the researchers observed the preservation of the fractional area shortening, an index of systolic function. In the mice models, the compound had shorter QRS intervals (preserved ventricular conduction) in comparison to the animals that were treated with a placebo. Results in DKO (double knockout) were similar, as the researchers observed that treatment with PB-1046 moderated the QRS prolongation.

Results from the in vivo analysis revealed that the treatment with PB1046 was able to improve cardiac contractility (elevated maximal rate of pressure rise dp/dtmax — an index of systolic function) and relaxation (Tau constant of relaxation).

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In MDX mice, PB1046 was found to protect against contraction-induced damage on isolated extensor digitorium longus (EDL) muscles during skeletal muscle evaluation. In addition, in MDX mice, the treatment with PB1046 lessened the gastrocnemius collagen content (an indicator of fibrosis), and also the collagen content in MDX mice heart muscle.

“Results of this pre-clinical study support the continued advancement of PB1046 into clinical trials for cardiomyopathy in DMD and BMD patients,” said Jonathan Mow, Chief Executive Officer of PhaseBio in the news release. “Moreover, this novel approach might serve as a complementary therapy to other DMD compounds in clinical development.”