University of Pennsylvania News, Medlinx, February 24, 2020

Diabetes adults are at an increased risk of fracturing a bone as compared to the general adults. If they do break one, it will take longer time to heal than normal individuals. In the March issue of Biomaterials, Henry Daniell, Shuying (Sheri) Yang, and colleagues at Penn’s School of Dental Medicine share favourable outcomes from an animal model wherein a plant-grown protein drug enhances recovery of a bone fracture. The study, which utilized the protein insulin-like growth factor-1 (IGF-1), demonstrated that an orally delivered, shelf-stable medication grown in lettuce plants could encourage the growth of bone-building cells and stimulate bone regeneration.

The corresponding author on the paper, Daniell, states that “it’s remarkable how one protein influenced fracture healing”. The novel drug for diabetic patients with a fracture needs repetitive injections and hospital visits and, therefore, patient adherence is low. Over here an oral drug once a day can be given and faster healing was seen. The paper’s co-corresponding author, Yang states that “Fracture healing is an essential health issue, particularly for diabetes patients”. They tend to have lowered bone repair and escalated fracture risk, introducing a treatment challenge. Delivering this current human IGF-1 though eating lettuce is potent, easily delivered, and an appealing option for patients. The study offers a novel and ideal therapeutic alternative for diabetic fracture and other musculoskeletal diseases.

The study utilized the plant-based drug composition platform that Daniell has established for several years, which involves presenting a protein of interest into plant cells, encouraging them to begin revealing that gene in their cells, ultimately developing that protein in their leaves which can be harvested and utilized in an oral therapy. In the current case, the goal was a novel IGF-1, a protein essential for bone and muscle health. Lower levels of IGF-1 in the blood are recognised to be correlated with an escalating risk of breaking a bone.

From previous work emphasis on muscular dystrophy was carried out with former Penn Dental Medicine faculty member Elizabeth Barton, now at the University of Florida, the researchers considered that a specific form of IGF, a precursor of the protein that involves a separate component termed as an e-peptide, probably to encourage reproduction superior to mature IGF-1 lacked the peptide. Present IGF1 utilized in the clinic not only has insufficient e-peptide but also glycosylated, a less active form. The team performed methods that Daniell has refined to highly convey the human version of IGF-1 in plant leaves and eliminate the antibiotic resistance gene that is utilized to choose for plants growing the target protein, critical steps to receive a therapy available for clinical use. They paired the IGF-1 precursor protein with another protein, CTB, which assist ferry the fused proteins from the digestive tract into the bloodstream. After cultivating the transgenic lettuce plants, they freeze-dried and powdered the leaves, certifying the outcome was shelf-stable for aproximately three years.

In both mouse and human cells, the investigators revealed that the plant-derived drug generated a variety of cell types which includes oral-tissue cells and osteoblasts, or bone-building cells, to develop and differentiate, or spilt to create a variety of distinct cell types. Moving next to estimate the performance of the drug in animal models, the investigators primarily provide that feeding mice the plant-based product had their IGF-1 levels enhanced. And in the end, in a diabetic mouse model, they determined that feeding it to animal’s improved bone volume, density, and area, signs of a more robust healing process. Daniell states that “they are expecting to find partners to elaborate this work as there are a plenty of diabetes people who could benefit from a therapy like this”.

In future study, the investigators hope to proceed establishing the plant-growing IGF-1 to transfer it to the clinic, not simply for bone fracture healing but also for other musculoskeletal problems as well, including osteoporosis and bone regeneration following cancer.