Early Translational IV
$4 411 388
Cleft palate is among the most common of all birth defects and affects about one in 1,500 births each year in the U.S. alone, resulting in physical, medical, social, emotional, and developmental problems in affected children in addition to the high health care costs. Current treatment requires an initial surgical closure of the cleft, orthodontic dental care, speech therapy, bone grafting, and multiple surgeries over the course of 18 years. Thus, there is a pressing need to develop new and effective methods for treatment to provide young patients with a safer and more efficient option that will result in a complete and permanent closure of the palatal cleft shortly after birth. This application focuses on developing a new and innovative bone product which can be customized to meet the needs of individual patients. This product utilizes a novel scaffold that supports efficient bone regeneration using the patient’s own stem and progenitor cells. Cleft palate can be detected prenatally by ultrasound and confirmed by a physical examination after birth allowing the collection of the necessary stem and progenitor cells for the customized product. If successful, this approach will eliminate the need for multiple surgeries and correct the problem early in life providing a substantial benefit to infants and children.
Statement of Benefit to California:
Cleft palate is the most common birth defect (1 in 1,500) and has an extensive socioeconomic impact on the State of California. Most children born with clefts require ongoing care that generally involves multiple surgeries and frequent visits to health care professionals. A recent study by the Centers for Disease Control and Prevention has shown that the average expenditure for an infant with cleft palate is approximately $100,000. Another study by ReSurge International estimated the lifetime economic impact of cleft palate repair to be between $152,372 and $375,412 per affected individual. In consideration of the socioeconomic burden/impact imposed upon the State of California, the technology proposed could dramatically reduce millions of dollars in direct and indirect medical costs. In addition to the overall economic benefit, the intent is to provide the technology to all patients including those through special needs programs geared towards reducing the costs to the patient and the State of California once this product is commercialized. The State of California will also generate revenue from license fees and royalties from worldwide sales of the scaffold which is the basic building block of the proposed product. If successful, this technology will result in the development of other stem cell-based orofacial and orthopedic treatments in California and subsequent revenue generation.
This application for a development candidate award focuses on creating a bone product for cleft palate repair. Cleft palate is a congenital condition in which an opening exists in the roof of the mouth and is among the most common birth defects, affecting 1/1500 newborns in the U.S. Current treatment requires multiple surgeries over the course of 18 years. The applicant proposes using autologous cells in combination with a scaffold to create a vascularized bone autograft product that will grow with the patient, eliminating the need for multiple surgeries. The major aims of this proposal are 1) to compare the efficiency of cleft palate repair in an in vivo model using scaffolds seeded with one of two different autologous cell sources, 2) to determine whether the addition of autologous endothelial progenitor cells improves the vascularization of the scaffold/mesenchymal cell bone grafts, and 3) to evaluate the safety and effectiveness of human mesenchymal cells with or without addition of human endothelial progenitor cells seeded into the scaffold for forming bone grafts in an immunosuppressed in vivo model. Objective & Milestones - Reviewers stated that the milestones lacked clear, quantitative, and translationally relevant criteria for success. - The milestones prioritize demonstration of pre-clinical efficacy of a very complicated product without much emphasis on the production process. Rationale & Significance - Reviewers agreed that this application addresses a significant congenital defect. However, some reviewers felt that the proposed method was prohibitively costly and likely to be only incrementally better than current surgical procedures. It was not clear why this construct was expected to result in fewer secondary surgical procedures than current methods. Feasibility & Design - The preliminary data were insufficient to convince reviewers that the cells and scaffold would have the desired properties. In addition, little evidence was provided that vascularization of the graft would occur. - There was a lack of information regarding the seeding and incubation of the cells on a three-dimensional construct prior to implantation, which was felt to be a critical step in developing this product. - Reviewers cited the lack of comparisons with standard treatments such as acellular dermal scaffold grafts and flap repair as a major deficiency in the description of the experimental plan. - Reviewers felt the experimental design was overly complex and were concerned that some of the most relevant outcome measures such as fistula or velopharyngeal inadequacy (VPI) were not being measured. - The proposed in vivo study is too underpowered to draw meaningful conclusions. Qualification of the PI (Co-PI, Partner PI, if applicable) & Research Team - The research team appeared generally capable; however, there is no evidence the PI previously has led a project of this complexity and magnitude. Collaborations, Assets, Resources, & Environment - Overall, the reviewers did not highlight any relevant concerns. Responsiveness to the RFA - The reviewers deemed this application to be responsive to the RFA.