Caspase Inhibitors and Inhibitors of Apoptosis in the Treatment of Infection Associated Preterm Delivery and Poor Pregnancy Outcome

Tech ID: equ000026

 

Introduction

Premature birth is a common problem in the US. Infection is the most common cause of preterm delivery and stillbirth globally. Infection plays a role in approximately 50% of total and 80% of early preterm deliveries (<32 weeks of gestation) in US. However, there are no effective prevention strategies or treatments. Recent studies found antibiotics do not offer a statistically significant prevention of preterm delivery. In some clinical trials, antibiotic treatment of intrauterine infections has been associated with even worse outcomes. Therefore, there is a definite need for alternative/complementary treatments to prevent infection induced preterm delivery.

Researchers at Cedars-Sinai have identified caspase inhibitors as new treatment for infection-associated preterm delivery.

 

Technology Description

Approximately 11% of all live births in the US are preterm. It is the leading cause of infant mortality and morbidity and costs >4 billion dollars/year. Although the etiologies of preterm birth are not clearly known, up to 80 percent of early preterm births (<32 weeks) are associated with intrauterine infection.

 

Caspases and apoptosis are thought to play a role in infection-associated preterm-delivery. Studies in mouse models suggest increased apoptosis in the placentas and membranes of the animals exposed to microbial antigens. Dr. Equils and colleagues at Cedars-Sinai Medical Center have previously showed that microbial antigens activate apoptotic machinery in the human placental cells. They also demonstrated in vitro treatment with pancaspase inhibitor, Z-VAD-FMK, protects trophoblasts from microbial antigen-induced apoptosis.

 

Dr. Equils et al further showed in preclinical in vivo studies that administration of pancaspase inhibitor Z-VAD-FMK delayed infection-induced preterm-delivery in mice. A topical formulation of Z-VAD-FMK is suggested to be safe and useful to delay infection-induced preterm-delivery.

 

Applications

• The technology can be developed into novel treatment and prevention method of infection-associated preterm delivery.

 

Intellectual Property

US 8,828,950 granted.

 

Publications

• Equils et al. Pretreatment with Pancaspase Inhibitor (Z-VAD-FMK) Delays but Does Not Prevent Intraperitoneal Heat-Killed Group B Streptococcus-Induced Preterm Delivery in a Pregnant Mouse Model. Infect Dis Obstet Gynecol. 2009;2009:749432. [LINK]

 

Patent Information:
For Information, Contact:
Wenyue Du
Associate - IP Management & Licensing
310-423-2241
wenyue.du@cshs.org
Inventors:
Ozlem Equils
Charles Simmons
Calvin Hobel
Keywords:
Infectious Diseases