2017 Little Giraffe Foundation Neonatal Grant Awards

After long deliberations, Little Giraffe Foundation voted to fund 17 initiatives for 2017, totaling over $41,000 – 3 Neonatal Research Grants to forward medical care for premature babies and 14 NICU Support Grants designed to improve the lives of the families and babies in the NICU.

 

Neonatal Research Grants

Boston Children’s Hospital, Harvard Medical School, Boston, MA - $10,000 Awarded

Research: Assessing the immunomodulatory capacity of mesenchymal stem (stromal) cell derived-exosome subtypes in models of bronchopulmonary dysplasia

Gareth R Willis, PhD – PI, Fellow – postdoctoral, Division of Newborn Medicine and Department of Pediatrics, Boston Children’s Hospital, Harvard Medical School

With no effective single therapy to prevent or treat bronchopulmonary dysplasia (BPD), a multifactorial chronic lung disease of preterm infants, the need for new therapies is urgent. BPD impacts the pulmonary and overall health of ~15,000 premature infants in the United States annually. It occurs predominantly in preterm infants receiving oxygen therapy and mechanical ventilation, and is characterized by lung growth arrest, diminished alveolar and blood vessel development and impaired pulmonary function, which collectively contributes to life-long cardio-respiratory morbidity. Our preliminary data has found that a bolus dose mesenchymal stem (stromal) cell-exosomes (MSC-exos) provide drastic histological and functional improvements in an established preclinical model of BPD. The overarching goal of this proposal is to support the preclinical development of MSC-exo therapeutics for the treatment of BPD. Specifically, the objective of is to: (i) isolate the bioactive exosome subtype (ii) explore therapeutic mechanism(s)-of-action (iii) demonstrate immunomodulatory / therapeutic actions of MSC-exo subtypes in vivo. Our working hypothesis is that MSC-exos (specifically the TSG101/Alix enriched MSC-exo subtype), through immunomodulatory pathways that dampen lung inflammation, inhibit the development of lung vascular and parenchymal injury. To test this hypothesis, we aim to isolate and characterize MSC-exo subtypes, and test their therapeutic and immunomodulatory effects in vivo using an established mouse model of BPD.

 

The Children’s Mercy Hospital, Kansas City, MO - $10,000 Awarded

Research: ITGB2 (Integrin β2) Immunomodulatory Gene Variants in premature infants with Necrotizing Enterocolitis

Lovya George, MD – PI, Division of Neonatology, Department of Pediatrics, Children’s Mercy Hospital, Kansas City, MO

Venkatesh Sampath, MD – Mentor and Co- PI, Department of Pediatrics, Children’s Mercy Hospital, Kansas City, MO

Necrotizing enterocolitis (NEC) is a devastating intestinal disease in premature infants with a mortality of 20 - 35%1. The NICHD estimates that NEC affects about 9,000 out of the 480,000 infants born preterm each year in the United States and is the leading cause of death in this population2. Despite extensive research, outcomes of NEC have remained unchanged over the last three decades. The total annual cost of caring for infants with NEC in the United States is estimated at $500 million to $1 billion3. A Critical gap in knowledge that has limited our ability to decrease NEC mortality is incomplete understanding of how it develops and why it affects only a select few infants. Although NEC is a multi-factorial disease, known risk factors cannot fully account for the variability in susceptibility to NEC. This has led to the recognition that genetic factors play a role in NEC susceptibility. Studies have shown that genetic variation in immune genes that regulate intestinal responses to gut microbiota can modulate the risk of NEC4-6. Toll like receptor (TLR) proteins regulate immune responses to bacteria in the gut and are critical for maintenance of bacterial tolerance. TLR4 is a ligand for bacterial lipopolysaccharide (LPS). There is increased expression of TLR4 in the premature intestine and activation of TLR4 by enteric bacteria, known to be a central event in NEC pathogenesis7, leads to increased epithelial injury and reduced epithelial repair. Animal studies suggest that loss of TLR4 signaling protects against experimental NEC. Our lab has published data on SIGRR (Single Immunoglobulin Interleukin-1 Related Receptor) gene variants that may increase susceptibility to NEC through loss of inhibition of TLR4- mediated inflammation5 and TLR genetic variants NFKB1 and NFKB1A which are associated with NEC6.

Integrin β2 (ITGB2) as a genetic locus for NEC susceptibility: β2 integrins are involved in fine tuning of TLR- mediated inflammatory responses8. The ITGB2 gene has an established role in T cell development and function and mutations in ITGB2 have been found to be associated with disease phenotypes including Leucocyte Adhesion Deficiency (a primary immunodeficiency disease),chronic colitis and Hirschsprung’s associated Enterocolitis9(another severe intestinal inflammatory phenotype specific to neonates). Deficiency of ITGB2 has been shown to cause hyper-responsiveness to TLR stimulation8. As TLR signaling plays a central role in the pathogenesis of NEC, we speculate that loss of function ITGB2 genetic variants would predispose premature infants to NEC. Preliminary data from our lab (see below) suggest that ITGB2 variants are enriched in infants with NEC, hence supporting a potential pathogenic role.

 

University of California - Los Angeles, Los Angelos, CA - $10,000 Awarded

Research: Targeting Epithelial Membrane Protein 2 (EMP2) in retinopathy of prematurity

Alison Chu, MD – PI, Assistant Professor-in Residence, Department of Pediatrics, David Geffen School of Medicine, University of California-Los Angeles

Madhuri Wadehra, PhD – Co-PI, Associate Professor, Department of Pathology, David Geffen School of Medicine, University of California-Los Angeles

Retinopathy of prematurity (ROP) is a disease exclusively seen in premature neonates, and can result in devastating neurodevelopmental consequences due to long-term vision impairment and even blindness. The exposure of premature neonates to hyperoxia and then normoxia, results in high levels of vascular endothelial growth factor (VEGF) and ultimately abnormal retinal neovascularization. Current therapies for ROP include anti-VEGF treatments such as bevacizumab and ranibizumab. However, studies have shown that both of these agents can cause systemic suppression of VEGF. As VEGF plays a critical role in ocular homeostasis required to maintain vascular integrity, prolonged VEGF inhibition has been shown to lead to cell death and vision loss in animal models as well as in human randomized clinical trials. Thus, more specific therapies are needed. To this end, we propose to study the utility of targeting EMP2 as a more specific agent against ROP. EMP2 is highly expressed in retinal pigmented epithelia (RPE), a cell type implicated in ROP disease pathogenesis. In this proposal, we test two hypotheses: i) EMP2 is upregulated in RPE cells; and ii) anti-EMP2 antibodies will reduce RPE derived VEGF in vitro and in animal models.

 

NICU Support Grants

 

  • Comanche County Memorial Hospital, Lawton, OK -- to receive $800 toward their Pics for Preemies program for cameras and SD Disks
  • Children’s Minnesota, Minneapolis, MN -- to receive $1,000 for food and hygiene products for NICU parents
  • Baptist Health Floyd, Floyd Memorial Foundation, New Albany, IN -- to receive $650 toward mamaRoo infant seats for NICU babies
  • Epic Homeschool Network, Inc., Austell, GA -- to receive $1,000 toward their Gift Bag Program to provide books/toys to NICU families at WellStar Cobb Hospital in Austell, GA
  • The Tiny Miracles Foundation, Darien, CT -- to receive $1,000 toward their NICU Pantry Program for stocking food in the family rooms at five area hospitals
  • The Family Childbirth & Children’s Center at Mercy Medical Center, Baltimore, MD -- to receive $650 toward their Soothing Care to NICU Infants Program for mamaRoo infant seats and corresponding seat inserts
  • Good Samaritan Hospital, Los Angeles, CA -- to receive $1,000 toward their Be There for Baby Program for food vouchers and transportation assistance for NICU families
  • University of Mississippi, Children’s of Mississippi Hospital, Jackson, MS -- to receive $1,000 toward The Kangaroo Care Project for Joeyband SleepBelts for NICU infants
  • Franciscan Health Foundation-Lafayette, Lafayette, IN -- to receive $390 for car seats for discharged NICU babies
  • Queens Hospital Center, New York City, NY -- to receive $650 toward mamaRoo infant seats and corresponding seat inserts for NICU infants
  • Children’s Hospital Foundation, Norton Children’s Hospital, Louisville, KY -- to receive $1,000 toward their Food and Gas Voucher Program for gas and restaurant gift cards to NICU families
  • Rockdale Medical Center, Conyers, GA -- to receive $1,000 toward their NICU Family Support Program for gas gift cards, journals, children’s books, and meal cards for eligible families
  • Franciscan Health Foundation-Chicago Heights, Chicago Heights, IL -- to receive $999 for 111 sleep sacks for NICU infants to aid in safe sleep practices
  • Edward Hospital, Naperville, IL -- to receive $500 for their Beads of Courage Program for NICU families


Upcoming Events!

 

 

Please consider donating a toy to a preemie during this particularly difficult time for families with babies in the NICU!