A long-acting prolactin to combat lactation insufficiency

Human infants are born to breastfeed. While 50% of lactating persons struggle to make enough milk, there are no governmentally-approved drugs to enhance lactation[1][1]. Here, we engineer a variant of the naturally-occurring driver of lactation, the hormone Prolactin, to increase its serum half-life and produce a viable drug candidate. Our engineered variant, Prolactin-eXtra Long-acting (Prolactin-XL), is comprised of endogenously active human prolactin fused to an engineered human IgG Fc domain designed to overcome the unique drug development challenges specific to the lactating person-infant dyad. Our Prolactin-XL has a serum half-life of 70.9h in mice, 2,625-fold longer than endogenously active prolactin alone (70.9h v. 0.027h). We demonstrate that Prolactin-XL increases milk production and restores growth of pups fed by dams with pharmacologically-ablated lactation. We show that Prolactin-XL-enhanced lactation is accompanied by reversible, lactocyte-driven changes in mammary gland morphology. This work establishes long-acting prolactins as a potentially powerful pharmacologic means to combat insufficient lactation. ### Competing Interest Statement The authors have declared no competing interest. All sequences used in this work are listed in the supplement. All the other data that support the findings of this study are available from the corresponding author upon request. [1]: #ref-1