Genetically Engineered Mesenchymal Stem Cells for the Treatment of Vertebral Compression Fractures.

Funding Type: 
Disease Team Therapy Development - Research
Grant Number: 
ICOC Funds Committed: 
Public Abstract: 

Approximately 10 million people in the United States currently have osteoporosis, and an additional 34 million people are at risk for osteoporosis. Osteoporotic vertebral compression fractures (VCFs) are the most common fragility fractures in the US; there are approximately 700,000 such injuries each year, twice the rate of hip fractures. Approximately 70,000 VCFs result in hospitalization each year, consuming enormous amounts of health care resources. Currently, treatment is focused primarily on prevention. When fractures occur in patients with osteoporosis, treatment options are limited because open surgery with implants often fails. In recent years, new therapies involving injection of cement into the fractured vertebra (such as vertebroplasty) have been developed. Unfortunately, these procedures do not regenerate bone tissue and carry risks of cement leakage and emboli. Recent publications in a leading medical journal question the effectiveness of those procedures. Based on these studies the American Academy of Orthopaedic Surgeons issued a set of new guidelines and recommended against the use of vertebroplasty.

We need a new biological treatment that will promote repair of such fractures in a safe and efficient manner. Our plan is to develop a therapy that uses adult mesenchymal stem cells (MSCs) that are genetically engineered to express a bone-forming gene, bone morphogenetic protein 6 (BMP6). These cells have been shown to promote bone formation and fracture repair in numerous studies. Specifically, we intend to use allogeneic ("off the shelf") human MSCs. These cells will be genetically engineered with BMP6 DNA in a virus-free method, using technology currently approved for clinical use. BMP6–engineered MSCs not only secrete BMP6 protein and promote bone formation but also differentiate into bone-forming cells themselves. This combined effect leads to fast and robust bone formation, which could be an attractive therapy for a variety of clinical conditions involving bone loss. An image-guided injection of BMP6–overexpressing MSCs into a fractured vertebra could lead to rapid fracture repair and shortened hospitalization time. We propose to use allogeneic, off-the-shelf, MSCs, which do not require the patient to undergo additional medical procedures such as bone marrow aspiration. Whereas use of autologous cells is limited by the number of cells that can be obtained from the patient, use of allogeneic cells is not limited by cell number. If successful, this therapeutic strategy could revolutionize the treatment of patients with VFCs, offering a minimally invasive biological solution. We plan to analyze aspects of efficiency and safety of use of the proposed therapy in a pre-clinical model, which will enable us to submit an approvable Investigational New Drug application (IND) to the Food and Drug Administration (FDA) by the end of the 4-year project.

Statement of Benefit to California: 

Approximately 10 million people in the United States have osteoporosis, while an additional 34 million have low bone mass. The lifetime incidence of fragility fractures secondary to osteoporosis in women older than 50 years of age is approximately 1 in 2, and that in men of the same age is 1 in 4. Osteoporosis-related vertebral compression fractures (VCFs) are the most common fragility fractures in the United States, accounting for approximately 700,000 injuries per year, twice the rate of hip fractures. Approximately 70,000 VCFs result in hospitalization each year, with an average hospital stay per patient of 8 days. Fragility fractures due to osteoporosis also place a severe financial strain on the health care industry. Estimates show there were approximately 1.5 million osteoporosis-related fractures in the United States in 2001, the care for which cost about $17 billion. Moreover, as the number of individuals over the age of 50 continues to increase, costs are predicted to rise to an estimated $60 billion per year by 2030. VCFs previously received limited attention from the spine care community. This oversight may be a result of the perception that VCFs are benign, self-limited disorders or that treatment options are limited. However, it has become clear that VCFs are associated with significant functional impairment and increased mortality, even in patients not presenting for medical evaluation at the time of fracture. Current treatment of osteoporotic patients is mostly focused on prevention of VCFs. There are few treatment options when VCFs actually occur. Since open surgery involves morbidity and implant failure in the osteoporotic patient population, nonoperative management, including medications and bracing, is usually recommended for the vast majority of patients. Unfortunately, large numbers of patients report intractable pain and an inability to return to activities. Currently there is no efficient biological solution for the treatment of VCFs. In the proposed study we will continue to develop a biological therapy to accelerate repair of VCFs. This treatment will rely on adult stem cells that have been genetically engineered to overexpress an osteogenic gene, BMP6, by using a nonviral technique that is clinically approved. It will also involve an injection of these cells into the fracture site, instead of a percutaneous injection of a polymer, which does not restore lost bone tissue. Data generated from this study could potentially revolutionize the treatment of vertebral fractures and other complex fractures in patients suffering from osteoporosis. This will benefit the citizens of California by reducing loss of workdays, duration of hospital stays, and operative costs, and by improving quality of life for Californians with osteoporosis, who are at risk for VCFs.