Disease Team Therapy Planning I
It is anticipated that there will be approximately 100,000 diagnosed vertebral compression fractures (crush fractures of the spine) among Californians in 2011. Most of these fractures will be the result of osteoporosis of the bones in the spine. Take, for example, the case of Mr. G. Mr. G. was an active 70-year-old life-long resident of [REDACTED]. He was the first in his family to attend college, receiving his undergraduate degree from [REDACTED]. He is the CEO of a company expanding into markets in Latin America. Four months ago he experienced the acute onset of low back pain upon bending over and lifting his carry-on luggage to the overhead compartment on his flight to a “new market” city. He was seen in the emergency room and diagnosed with compression fractures of two adjacent vertebral bodies in his lower back; he had a family history of osteoporosis but he did not know that he was affected by the disorder. He was confined to bed and then a wheel chair for a total of five weeks. At four months post fracture he is just now back to work part-time. He lost an inch in height and now endures a permanent change in the shape of his lower back. He suffers from chronic low back pain has yet to resume flying to promote his business. He reports that he will “probably never get back to where I was before the fracture” Mr. G’s story is not uncommon among Californians. Up to 50% women and 20% men over age 50 will suffer an osteoporosis-related fracture in their remaining lifetime. Aging can significantly reduce the number of bone forming stem cells in the body, a fundamental cause of osteoporosis, The loss of adequate bone forming stem cell activity over time results in a decrease in bone strength and the development of osteoporotic “fragility” fractures. Current medical management of osteoporotic vertebral compression fractures such as those suffered by Mr. G includes pain control and best rest. With more severe fractures, causing persistent pain and disability, surgery is usually indicated. However, current surgery options are limited to injection of a fractured vertebral body with a cement compound that is toxic to living tissues including bone stem cells. Once set, the unnatural stiffness of the cement relative to bone can increase the risk of refracture of the treated vertebrae or cause new fractures in the adjacent vertebrae. In addition, cement leakage and entry to the blood stream can cause life-threatening complications. Thus, current therapies for osteoporotic vertebral compression fracture are less safe than possible and do not address the fundamental stem cell defect in osteoporosis. The current proposal seeks to deploy a novel bone stem cell inducing biologic device, [REDACTED], in crushed vertebral bodies to relieve the fracture victim’s pain and disability. It is our goal to establish a safe way to restore living, long-lasting bone to sites where it has been lost.
Statement of Benefit to California:
This well-developed proposal aims to enable IND submission for the use a novel growth factor to direct the differentiation of human endogenous stem cells for bone regeneration. This highly multi-disciplinary project has many near-term and long-term benefits to the State of California. 1. California’s unmatched climate is attractive to people of all ages, particularly the elderly. Unfortunately, a large fraction of the aged population suffers from osteoporosis. In 1998, the health care burden for osteoporosis exceeded $2.4 billion in California alone. By promoting the repair of both normal and healing-impaired bone in a safe and effective manner, our mature technology will reduce the long term health care burden for California’s public health insurance program. 2. Besides direct health cost, bone injuries and diseases can result in hospitalizations and long term disabilities that can lead to sick days and lost productivity. The hard working Californians are responsible for California’s annual gross domestic product of $1.8 trillion, which rank our state among the top eight largest economies in the world. By promoting the restoration of bone lost to osteoporosis in a safe and effective manner, our mature technology will reduce the loss of work productivity at the front end, reduce work disability costs, and reduce the loss of state income tax. 3. California boasts a highly diverse population with numerous ethnic groups. While this diversity offers amazing opportunities for cross cultural discoveries, some ethnic groups (e.g. Latinos and some of Asian descent) may be disadvantaged in terms of donor matches for traditional stem cell sources. Our endogenous stem cell therapy eliminates the need for donor matches and can benefit these minorities and reduce the long term health care burden for California’s public health insurance program. 4. This project directly adds jobs at [REDACTED] and at the California-based companies that are involved in this project. 5. This project will procure supplies and equipment from California-based companies. 6. This project will produce intellectual property [REDACTED] 7. This mature project is precisely the type of cutting-edge, ethical, multi-disciplinary stem cell project that Californians imagined when they approved proposition 71 in 2004. The establishment of CIRM has transformed the research infrastructure at [REDACTED], increased our ability to recruit world-class stem cell scientists and attracted the attention of superb scientists from other disciplines to this new field. Working together, our team has compiled an impressive list of accomplishments and we are confident that we can successfully take this project to IDE submission in a timely fashion. Funding of this project will fulfill the promise of proposition 71.
EXECUTIVE SUMMARY Project Synopsis The project proposes to develop a novel treatment for vertebral compression fracture (VCF), which is common in patients with osteoporosis. This proposal seeks to develop a combination device that would promote bone regeneration and repair of VCF through induction of endogenous stem cells and relieve pain and disability. The project seeks to complete preclinical studies, submit a regulatory filing for an Investigational Device Exemption (IDE), and complete enrollment of a Phase I clinical trial within the four-year span of the project. Significance and Impact - Current treatment for VCF is cement; however, leakage can lead to fracturing of adjacent vertebrae. The product proposed here might have similar efficacy but with an improved safety profile. Although the preclinical studies did not address the possibility, the device could reduce the frequency of adjacent fractures. - There is a significant unmet clinical need to treat VCF, and this product could provide a viable alternative to currently available treatments for VCF. Project Rationale and Feasibility - The rationale is unclear for why the biologic device is not being compared against the device material alone in the proposed clinical trial to show benefit of the addition of the protein biologic component. - One reviewer noted that the control treatment method in the clinical design of this proposed study was shown to be ineffective by two different studies published in the New England Journal of Medicine. - There was a lack of detail regarding the novel biologic component of the device, how and where it would be produced, and how it would be attached or incorporated into the device. - Preclinical data were deemed reasonable and moderately convincing, but the lack of data showing the direct contribution of the biologic component of the system and that it improves outcome was a weakness. -One reviewer recommended conducting additional studies to determine the types and rates of adverse events observed with the combination of surgical mesh and the allograft. Principal Investigator (PI) and Planning Leader - PI has a strong academic publication record in osteogenesis and has good clinical experience but will more likely be playing an administration role in this project. - The planning leader appears to be well qualified and has experience in working with the FDA. - Overall the team seems well qualified.
- This application scored below the initial scientific merit funding line, no programmatic reason to fund the application was proposed, and the GWG voted to place the application in Tier 3, Not Recommended for Funding.