A promising new strategy to help broken bones heal faster

February 24, 2020

People with diabetes are at a higher risk of fracturing a bone than the general population. And if they do break one it also takes longer than normal to heal.

In the March issue of Biomaterials, Henry Daniell, Shuying (Sheri) Yang, and colleagues at Penn's School of Dental Medicine share promising findings from an animal model in which a plant-grown protein drug sped healing of a bone fracture. The work, which used the protein insulin-like growth factor-1 (IGF-1), showed that an orally delivered, shelf-stable medication grown in lettuce plants could stimulate the growth of bone-building cells and promote bone regeneration.

"It's amazing how one protein impacted fracture healing," says Daniell, corresponding author on the paper. "The current drug for diabetic patients with a fracture requires repetitive injections and hospital visits and as a result patient compliance is low. Here we gave an oral drug once a day and saw healing to be greatly accelerated."

"Fracture healing is a significant health issue, especially for patients with diabetes," says Yang, the paper's co-corresponding author. "They tend to have reduced bone repair and increased fracture risk, presenting a treatment challenge. Delivering this novel human IGF-1 though eating lettuce is effective, easily delivered, and an attractive option for patients. The study provides a new and ideal therapeutic option for diabetic fracture and other musculoskeletal diseases."

The study employed the plant-based drug production platform that Daniell has developed over many years, which entails introducing a protein of interest into plant cells, prompting them to begin expressing that gene in their cells, eventually producing that protein in their leaves which can be harvested and used in an oral therapy.

In this case, the target was a novel IGF-1, a protein important for bone and muscle health. Lower levels of IGF-1 in the blood are known to be associated with an increased risk of breaking a bone.

From earlier work focused on muscular dystrophy conducted with former Penn Dental Medicine faculty member Elizabeth Barton, now at the University of Florida, the researchers believed that a particular form of IGF, a precursor of the protein that includes a separate component known as an e-peptide, was likely to stimulate regeneration better than mature IGF-1 that lacked the peptide. Current IGF1 used in the clinic not only lacks the e-peptide but is also glycosylated, a less active form.

The team used methods that Daniell has refined to highly express the human version of IGF-1 in plant leaves and remove the antibiotic resistance gene that is used to select for plants growing the target protein, crucial steps to get a therapy ready for clinical use. They paired the IGF-1 precursor protein with another protein, CTB, which helps ferry the fused proteins from the digestive tract into the bloodstream.

After growing the transgenic lettuce plants, they freeze-dried and powdered the leaves, confirming the product was shelf-stable for nearly three years.

"Fundamental to all these projects is we want to make the delivery of this drug affordable, comfortable, and possible to do at home," says Daniell.

In both mouse and human cells, the researchers showed that the plant-derived drug caused a variety of cell types, including oral-tissue cells and osteoblasts, or bone-building cells, to grow and differentiate, or divide to form a variety of different cell types.

Turning next to investigate the activity of the drug in animal models, the researchers initially showed that feeding mice the plant-based product caused their IGF-1 levels to increase. And finally, in a diabetic mouse model, they discovered that feeding it to animals improved bone volume, density, and area, signs of a more robust healing process.

"We're hoping to find partners to advance this work as there are a lot of people with diabetes who could benefit from a therapy like this," Daniell says.

In future work, the researchers hope to continue developing the plant-growing IGF-1 to move it to the clinic, not only for bone fracture healing but for other musculoskeletal problems as well, including osteoporosis and bone regeneration following cancer.
-end-
Daniell, and Yang's coauthors on the paper, all from Penn Dental Medicine, were first author Jiyoung Park, Guangqi Yan, Kwang-Chul Kwon, Min Liu, and Patricia A. Gonnella..

Henry Daniell is vice chair and W.D. Miller Professor in the Department of Basic & Translational Sciences in the University of Pennsylvania School of Dental Medicine.

Shuying (Sheri) Yang is an associate professor in the Department of Basic & Translational Sciences in the University of Pennsylvania School of Dental Medicine.

Funding for the study came from the National Institutes of Health (grants GM63879, HL107904, HL109442, HL133191, DE023105, and AR066101).

University of Pennsylvania

Related Diabetes Articles from Brightsurf:

New diabetes medication reduced heart event risk in those with diabetes and kidney disease
Sotagliflozin - a type of medication known as an SGLT2 inhibitor primarily prescribed for Type 2 diabetes - reduces the risk of adverse cardiovascular events for patients with diabetes and kidney disease.

Diabetes drug boosts survival in patients with type 2 diabetes and COVID-19 pneumonia
Sitagliptin, a drug to lower blood sugar in type 2 diabetes, also improves survival in diabetic patients hospitalized with COVID-19, suggests a multicenter observational study in Italy.

Making sense of diabetes
Throughout her 38-year nursing career, Laurel Despins has progressed from a bedside nurse to a clinical nurse specialist and has worked in medical, surgical and cardiac intensive care units.

Helping teens with type 1 diabetes improve diabetes control with MyDiaText
Adolescence is a difficult period of development, made more complex for those with Type 1 diabetes mellitus (T1DM).

Diabetes-in-a-dish model uncovers new insights into the cause of type 2 diabetes
Researchers have developed a novel 'disease-in-a-dish' model to study the basic molecular factors that lead to the development of type 2 diabetes, uncovering the potential existence of major signaling defects both inside and outside of the classical insulin signaling cascade, and providing new perspectives on the mechanisms behind insulin resistance in type 2 diabetes and possibly opportunities for the development of novel therapeutics for the disease.

Tele-diabetes to manage new-onset diabetes during COVID-19 pandemic
Two new case studies highlight the use of tele-diabetes to manage new-onset type 1 diabetes in an adult and an infant during the COVID-19 pandemic.

Genetic profile may predict type 2 diabetes risk among women with gestational diabetes
Women who go on to develop type 2 diabetes after having gestational, or pregnancy-related, diabetes are more likely to have particular genetic profiles, suggests an analysis by researchers at the National Institutes of Health and other institutions.

Maternal gestational diabetes linked to diabetes in children
Children and youth of mothers who had gestational diabetes during pregnancy are at increased risk of diabetes themselves, according to new research published in CMAJ (Canadian Medical Association Journal).

Two diabetes medications don't slow progression of type 2 diabetes in youth
In youth with impaired glucose tolerance or recent-onset type 2 diabetes, neither initial treatment with long-acting insulin followed by the drug metformin, nor metformin alone preserved the body's ability to make insulin, according to results published online June 25 in Diabetes Care.

People with diabetes visit the dentist less frequently despite link between diabetes, oral health
Adults with diabetes are less likely to visit the dentist than people with prediabetes or without diabetes, finds a new study led by researchers at NYU Rory Meyers College of Nursing and East Carolina University's Brody School of Medicine.

Read More: Diabetes News and Diabetes Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.