BridgeBio Creates ML Bio Solutions to Develop Therapy for Limb-Girdle Muscular Dystrophy Type 2
Rare Daily Staff
BridgeBio Pharma said it has established ML Bio Solutions as a new subsidiary to developing a substrate supplementation therapy for limb-girdle muscular dystrophy type 2i, a progressive and debilitating neuromuscular disease that results in loss of mobility and ultimately respiratory and cardiac failure.
Limb-girdle muscular dystrophy type 2i (LGMD2i) is an autosomal recessive disease wherein loss-of-function mutations in the FKRP gene lead to decreased glycosylation of alpha-dystroglycan (α-DG). Properly glycosylated α-DG anchors muscle cells to proteins outside of the cell in the extracellular matrix as well as shock absorber proteins inside of the muscle cells, such as dystrophin. In LGMD2i, α-DG has a defective sugar backbone, and thus cannot effectively bind these proteins to stabilize the muscle cell, leading to muscle cell fragility and damage under stress. Damaged and degenerating muscle cells can result in global loss of muscle strength. LGMD2i affects an estimated 7,000 patients across the United States and Europe. Presently, there is no approved treatment.
In creating ML Bio, BridgeBio intends to begin a natural history study of LGMD2i before the end of 2019, and to initiate interventional trials soon afterward to test its small molecule oral therapy BBP-418.
The McColl Lockwood Laboratory for Muscular Dystrophy Research at Atrium Health will continue to support the program alongside BridgeBio.
ML Bio’s compound BBP-418 aims to bypass the core metabolic defect in LGMD2i by providing a pro-drug to the other enzymes in the pathway that can be metabolized into the missing substrate in the α-DG sugar backbone. This therapeutic approach originates from the discovery and translational work of scientific co-founder Qi Long Lu, director of the McColl-Lockwood Laboratory for Muscular Dystrophy Research at Atrium Health.
“BBP-418 is a novel approach that targets LGMD2i at the source of disease, and exemplifies the BridgeBio mission of creating life-altering medicines by pairing well-understood genetically- driven phenotypes with treatments whose mechanisms target the sources of disease,” said Uma Sinha, chief scientific officer of BridgeBio Pharma.”
Formed in 2015 to create “life-altering medicines” that target genetic diseases that arise from defects in a single gene, BridgeBio’s pipeline includes more than 15 development programs ranging from early discovery to late-stage development, including two gene therapy candidates.
The company follows a capital efficient business model that involves licensing the rights and setting up subsidiaries to house each candidate in its pipeline. The subsidiaries share resources with the parent company and each other. BridgeBio said its early stage candidate subsidiaries have fewer than five-member teams that can grow as candidates reach human-testing stage.
Photo: Uma Sinha, chief scientific officer of BridgeBio Pharma