Issue SUMMER 2019 68 What’s INSIDE 1 Greeting 2 Research News 5 Awareness News 6 Lung Transplant Updates 8 Fundraising News 11 Report from Stichting ACD (Netherlands) 12 Report from The David Ashwell Foundation (UK) 13 Remembering Our Babies and Welcome to New Families 14 Safe Arrivals and Connect With Us Please see pages 2-4 for information about recent significant developments in ACDMPV research. The two research institutions discussed in the articles, Cincinnati and Baylor, are both recent NORD grant recipients. Thank you for supporting the ACDA and making research developments possible. Regards, Eliza Rista, President RESEARCH NEWS $50,000 for ACDMPV research closed on June 18, 2019. NORD has begun the review of all NORD GRANT UPDATES: submitted applications and will move forward with the selection process for the 2019 2018 NORD Grant: recipient. The previously announced 2018 NORD grant (see 2020 NORD Grant: Issues #63 and #64 of The ACDA is in the process of raising funds for ACDA Notes) in the amount a potential 2020 NORD grant. Please note the of $50,000 for ACDMPV minimum amount required for a NORD grant research was recently for ACDMPV research is $35,000. Please click awarded in June 2019 to Dr. HERE to donate. Csaba Galambos at University of Colorado Denver in Aurora, Colorado, USA for the study entitled, “The role of serotonin signaling in the pathogenesis of alveolar capillary dysplasia.” AT A GLANCE The ACDA initially presented Dr. Galambos’ Two possible therapeutic theory about the possible role of serotonin in approaches for ACDMPV ACDMPV patients in Issue #63 of ACDA (pending the development Notes, stating his prior study “contemplates a new area of exploration in both the of clinical trials): pathogenesis of and possible future Nanoparticle technology delivering a development of new therapeutic strategies for STAT3 protein to the lungs of ACDMPV ACDMPV. In the meantime, the next proposed babies, which could trigger the step of this research is to confirm whether or not ACDMPV patients display elevated development of blood vessels in the serotonin levels.” The ACDA will support Dr. lungs Galambos’ current research by facilitating the • Science Daily (June 19, 2019) collection of 24-hour urine samples of approved ACDMPV patients. • Medical Daily (June 20, 2019) Cell transplantation of c-KIT-positive Dr. Galambos is a pediatric pathologist and endothelial progenitor cells from donor prior NORD grant recipient for ACDMPV lungs, to increase the development of research in 2014. He has maintained a close pulmonary capillaries in ACDMPV working relationship with other key ACDMPV babies research institutions, including Baylor College of Medicine. Please read additional information (see pages 3- 4) about each of the above possible therapeutic approaches. Note: The two research institutions discussed in 2019 NORD Grant: the articles, Cincinnati and Baylor, are both The abstract submission deadline recent NORD grant recipients. Thank you for the previously announced for supporting the ACDA and making 2019 NORD grant (see Issue #67 significant research developments of ACDA Notes) in the amount of possible. ALVEOLAR CAPILLARY DYSPLASIA | ACDA Notes 2 Journal Article (AJRCCM) (Nanoparticle Baylor College of Medicine in Houston, the Technology): Kalinichenko lab analyzed genetic information from human ACDMPV cases to generate the The developmental first clinically relevant animal model of biology research group ACDMPV. Scientists used a gene editing at Cincinnati Children's method called CRISPR/Cas9 to generate mice Hospital Medical that faithfully mimic ACDMPV. The new Center in Cincinnati, laboratory model allowed researchers to Ohio, USA (see Issues pinpoint the ailment's cause and develop a #57, #62 and #63 of potential and desperately needed nanoparticle- ACDA Notes), recently based treatment. collaborated with the genetic research team The authors theorized that treating newborn at Baylor College of Medicine in Houston, mice with STAT3 would stimulate blood vessel Texas, USA to publish a manuscript entitled development in the lungs, but they had to “The S52F FOXF1 Mutation Inhibits STAT3 figure out how to get the protein to the Signaling and Causes Alveolar Capillary lungs…Researchers turned to nanoparticle Dysplasia” in the American Journal of technology to deliver a STAT3 mini-gene to Respiratory and Critical Care Medicine, which lungs of newborn mice. They created a novel can be found HERE. formulation for what are known as polyethylenimine (PEI) nanoparticles. Pending the development of a clinical trial, nanoparticle technology delivering a STAT3 The gelatin-like PEI nanoparticles can carry protein to the lungs of ACDMPV babies therapeutic genetic material to different parts may be a future possible therapeutic of the body by administering them to patients approach for ACDMPV, to trigger the intravenously. Different formulations of PEI development of blood vessels in the lungs. nanoparticles are currently being tested in Please read news articles published in Science clinical trials for adult cancer at other Daily (June 19, 2019) and Medical Daily (June institutions, according to study authors…This 20, 2019) for further details. From the Science stimulated blood vessel growth in the animals Daily article: and the formation of air sacs called alveolar.” "There are no effective treatments other than a "If the efficacy of PEI nanoparticles is lung transplant, so the need for new confirmed in the clinical trials under way for therapeutics is urgent," said Vlad Kalinichenko, adult cancer, PEI could be considered for MD, PhD, at the Cincinnati Children's STAT3 gene therapy in infants with Perinatal Institute Center for Lung ACDMPV," Kalinichenko said. "Considering Regenerative Medicine and lead study that ACDMPV is a rare disease, a multicenter investigator. "We identified a nanoparticle clinical trial would be needed to assess the therapeutic strategy to increase the number of efficacy of STAT3 gene therapy in ACDMPV alveolar capillaries and help preserve newborns and infants." respiratory function for at least a As background, the Kalinichenko Research subset of the babies with this Lab at Cincinnati was the winner of the 2017 congenital lung disease." NORD grant for ACDMPV research. The long- “In collaboration with the team of term goal of the Kalinichenko Research Lab is Pawel Stankiewicz, MD, at the "to discover novel therapeutic approaches and ALVEOLAR CAPILLARY DYSPLASIA | ACDA Notes 3 generate novel FDA-approved drugs for pulmonary capillaries in ACDMPV babies. treatment of these severe respiratory disorders." To learn more about the Kalinichenko Research Lab, please click Journal Article (AJRCCM) (Diagnostics): HERE and read about their current projects. The genetic research team at Baylor College of Medicine in Houston, Journal Article (AJRCCM) (Cell Texas, USA recently Transplantation): collaborated with an The developmental international team to biology research group publish a manuscript discussed above at entitled “Clinical, Cincinnati Children's Histopathological, and Hospital Medical Molecular Diagnostics Center in Cincinnati, in Lethal Lung Ohio, USA also Developmental Disorders” in the American recently collaborated Journal of Respiratory and Critical Care on another manuscript Medicine, which can be found HERE. entitled “Postnatal The research team examined a series of Alveologenesis Depends on FOXF1 Signaling pediatric lethal lung developmental disorders, in c-KIT+ Endothelial Progenitor Cells” in the including (1) ACDMPV, (2) acinar dysplasia American Journal of Respiratory and Critical (AcDys), (3) congenital alveolar dysplasia Care Medicine, which can be found HERE. (CAD), and (4) other unspecified primary The article focused on a severe pediatric lung pulmonary hypoplasias. The team reviewed disorder called Bronchopulmonary Dysplasia histopathological samples from lung biopsy or (BPD) with an objective to determine whether autopsy. c-KIT+ EC progenitor cells stimulate “The histopathological continuum in these alveologenesis (the formation of the alveoli) in lethal developmental disorders has made the neonatal lung. The conclusion of the study accurate diagnosis challenging. Over the past was that cell therapy involving c-KIT+ EC decade, genetic studies have revealed the progenitors can be beneficial for treatment of causative role of the FOXF1 gene or other BPD. nearby variants in chromosome 16 for In July 2019, the ACDA corresponded with Dr. ACDMPV patients. In contrast, the molecular Kalinichenko at Cincinnati (discussed above) bases of two of the other lethal lung to further understand the significance of this development disorders, AcDys and CAD, have important research and how it applies to remained poorly understood but the article ACDMPV. Pending the development of a discusses recent progress for these other clinical trial, cell transplantation of c-KIT- disorders, including disruption of the TBX4- positive endothelial progenitor FGF10-FGFR2 pathway. The team proposes cells from donor lungs may be that for a more precise diagnosis of lethal lung a future possible therapeutic developmental disorders such as AcDys and approach for ACDMPV, to CAD, a diagnostic pathway including whole increase the development of genome sequencing should be implemented.” ALVEOLAR CAPILLARY DYSPLASIA | ACDA Notes 4 AWARENESS NEWS Upcoming Date: Sci Foo Conference (David Ashwell): August 19, 2019 – Day of Hope Amelia Ashwell, ACDA mother to David “August 19th is about coming together as a Ashwell (March