This technology includes the use of a new class of molecules (nanomolar ALK2 inhibitor) to impede bone morphogenetic proteins (BMP) signaling for the treatment of Fibrodysplasia ossificans progressiva (FOP). FOP is a rare disease, characterized by malformation of the great (big) toes during embryonic development. Individuals with FOP have identical heterozygous activating mutation (R206H) in the gene encoding ACRV1 (also known as ALK2), a BMP type 1 receptor. This compound was created by replacing a quinoline moeity with a naphthalene moeity which gave rise to a class of molecules that are not susceptible to aldehyde oxidase (AO) metabolism, a major pathway for quinoline-containing molecules. Elimination of this metabolic pathway can have major benefits, such as increased systemic exposure, prevention of potential toxic effects of quinoline metabolites, and avoiding inter-subject variability based on AO polymorphism.
A nanomolar ALK2 inhibitor could conceivably be used as prophylactic, acute, or chronic therapy for patients with FOP.
This therapy is derived from a new, distinct class of compounds and would benefit those suffering from this disorder where there is currently no effective treatment available.