Regenerative medicine has the potential to provide novel therapies for a number of diseases affecting newborns. William A. Carey, M.D., seeks to find innovative treatments for two such disorders for which there currently are no cures.
Abnormal growth and development of the lung, as seen in bronchopulmonary dysplasia and congenital diaphragmatic hernia, is a common cause of death and disability in the neonatal population. Likewise, an arrest in the development of the human brain, as seen in periventricular leukomalacia, may lead to long-term abnormalities in neurodevelopment, such as cerebral palsy and mental retardation.
Dr. Carey is pursuing antibody- and stem-cell-based therapies for these pulmonary and neurological conditions using histological, biochemical, imaging and physiological techniques.
Research in the fields of stem cell engineering and lung recellularization could lead to treatments for what otherwise would be lethal abnormalities of lung development.
- Stem cell engineering. Dr. Carey and his collaborators are learning how to use induced pluripotent stem (iPS) cells to reverse the arrest of pulmonary alveolar and vascular development in a model of bronchopulmonary dysplasia.
- Lung recellularization. Dr. Carey and his collaborators also use iPS cells to recellularize the decellularized porcine lung matrix such that a functional, transplant-ready lung is generated. A lung so created with patient-derived iPS cells could be used to treat lethal degrees of pulmonary hypoplasia in cases of congenital diaphragmatic hernia.
Research in the field of neuroimmunology could provide safe and effective treatments for a variety of diseases affecting the central nervous system.
- Antibody-based therapy. Dr. Carey and his collaborators use recombinant forms of naturally occurring human antibodies to prevent and treat abnormal brain development in a murine model of periventricular leukomalacia. These antibodies soon will be tested in a phase I clinical trial of treatment of adult central nervous system disorders.
Significance to patient care
Bronchopulmonary dysplasia affects 10,000 babies annually in the U.S., leading to prolonged hospitalization, impaired developmental outcomes and even death.
More than 1,500 cases of congenital diaphragmatic hernia are seen each year in the U.S., with approximately 50 percent of these babies dying due to severe pulmonary hypoplasia.
Periventricular leukomalacia affects perhaps 25,000 babies in the U.S. each year, with lifelong impairments in movement, learning, behavior and self-care.
For each of the above conditions, there currently is no effective preventive strategy or curative treatment.
- Recipient, Loan Repayment Program Award, National Institute of Child Health and Human Development, National Institutes of Health, 2003-2007