Diabetes patients are more susceptible to bone fractures and take longer than usual to heal
A research paper from the Penn School of Dental Medicine in the United States has shown that a new “plant-grown protein drug” may be a boon for those suffering bone fractures. The drug — that uses the protein ‘insulin-like growth factor-1’ (IGF-1) — stimulates growth of bone-building cells and promotes bone regeneration, according to the study.
The finding may prove to be beneficial for those who have diabetes, as they are more susceptible to bone fractures. Diabetes patients also take longer than usual to heal from such injuries.
“It’s amazing how one protein impacted fracture healing,” said Henry Daniell, one of the study’s authors. “The current drug for diabetic patients with a fracture requires repetitive injections and hospital visits and as a result patient compliance is low,” he added.
The shelf-stable medication — grown in lettuce plants — was administered orally to patients, after which their healing was “greatly accelerated”, said Daniell.
A plant-based drug production platform developed by Daniell for many years was used in the study. The protein was created from this platform after the introduction of a protein of interest into the plant cells. The plant cells then express that gene, producing that protein in their leaves. The protein can then be harvested and used in oral therapy.
The researchers thus targeted the IGF-1, important for bone and muscle health. Those who have lower levels of IGF-1 in blood are prone to an increased risk of breaking bones.
Diabetes patients “tend to have reduced bone repair and increased fracture risk, presenting a treatment challenge,” said Shuying (Sheri) Yang, the study’s co-author.
“The study provides a new and ideal therapeutic option for diabetic fracture and other musculoskeletal diseases. Delivering this novel human IGF-1 though eating lettuce is effective, easily delivered, and an attractive option for patients,” she added.
How researchers developed the protein
Earlier work on muscular dystrophy had found that a particular IGF type — which included a separate component known as e-peptide and was an earlier form of IGF-1 — would stimulate regeneration better than IGF-1. the protein lacked the peptide and the form used in the clinic not only lacked the e-peptide, but was also a less active form (glycosylated).
Researchers used methods from this earlier work to express the human form of IGF-1 in plant leaves and then remove a resistance gene used to select for plants growing the target protein, steps which were significant to get the therapy ready for clinical use.
They then paired the precursor IGF-1 protein with another protein known as CTB, which transports fused proteins from the digestive tracts to the bloodstream.
The lettuce leaves were then freeze-dried and powdered to ensure the shelf-stability of the product for 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,” said Daniell.
Testing in mice
Oral-tissue cells and osteoblasts (bone-building cells) grew and differentiated to form a variety of cell types in mouse and human cells after the plant-derived drug was introduced.
Researchers then fed the drug to mice and found that IGF-1 levels in the non-diabetic rodents increased, while diabetic rodents showed an improvement in their bone density, volume and area. They also showed a vigourous healing process.
The researchers now aspire to move their research on IGF-1 to other musculoskeletal problems, including osteoporosis and bone regeneration following cancer.
The study on IGF-1 was published in the March edition of the journal Biomaterials. The research on muscular dystrophy was conducted by Elizabeth Barton, a former Penn Dental Medicine faculty member.
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