Future Clinical Targets

Neurodevelopmental Injury (NDI)

NDI occurs when premature infants affected by NEC have immune cells migrate from the gut to the brain, causing damage to brain cells. This results in abnormal neuronal communication and results in delayed learning and other disabilities for premature infants. The condition has a high morbidity rate, with survivors likely requiring long-term care. (Footnote: Sacchi C, Marino C, Nosarti C, Vieno A, Visentin S, Simonelli A. Association of Intrauterine Growth Restriction and Small for Gestational Age Status With Childhood Cognitive Outcomes: A Systematic Review and Meta-analysis. JAMA Pediatr. 2020 Aug 1;174(8):772-781. PMID: 32453414; PMCID: PMC7251506.) (Footnote: Bell EF, Hintz SR, Hansen NI, Bann CM, Wyckoff MH, DeMauro SB, Walsh MC, Vohr BR, Stoll BJ, Carlo WA, Van Meurs KP, Rysavy MA, Patel RM, Merhar SL, Sánchez PJ, Laptook AR, Hibbs AM, Cotten CM, D’Angio CT, Winter S, Fuller J, Das A; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Mortality, In-Hospital Morbidity, Care Practices, and 2-Year Outcomes for Extremely Preterm Infants in the US, 2013-2018. JAMA. 2022 Jan 18;327(3):248-263. doi: 10.1001/jama.2021.23580. Erratum in: JAMA. 2022 Jun 7;327(21):2151. PMID: 35040888; PMCID: PMC8767441.)

Broncho-Pulmonary Dysplasia (BPD)

BPD develops when the growth of blood vessels and alveoli (air sacs) in the lungs is disrupted, and the lung tissue becomes less flexible. If the disease does not result in morbidity(? death) it hinders neurocognitive development through adolescence and can result in chronic conditions like asthma and COPD later in life. (Footnote: Gilfillan M, Bhandari A, Bhandari V. Diagnosis and management of bronchopulmonary dysplasia. BMJ. 2021 Oct 20;375:n1974. doi: 10.1136/bmj.n1974. PMID: 34670756.)

Acute Respiratory Distress Syndrome (ARDS)

ARDS is one of the most common acute lung illnesses in adults and has exploded in prevalence since the start of the COVID-19 pandemic. The disease causes the lungs to become inflamed and filled with fluid, which can lead to scarring and breathing difficulties. By reducing inflammation with biotherapeutics, we aim to reduce the mortality rate of ARDS, which is currently 30%. (Footnote: Meyer NJ, Gattinoni L, Calfee CS. Acute respiratory distress syndrome. Lancet. 2021 Aug 14;398(10300):622-637. doi: 10.1016/S0140-6736(21)00439-6. Epub 2021 Jul 1. PMID: 34217425; PMCID: PMC8248927.)

Neurodegenerative
(Alzheimer’s, ALS, Parkinson’s)

Neurocognitive degeneration associated with multiple diseases such as Alzheimer’s Disease, Amyotrophic Lateral Sclerosis (ALS), or Parkinson’s Disease are debilitating diseases of aging and neuronal cell death that is driven by inflammatory cells in the brain. As the nervous system degenerates the disease affects mobility, balance, eating, breathing, bowel control, speech, and memory/cognition. (Footnote: Mawe GM, Browning KN, Manfredsson FP, Camilleri M, Hamilton FA, Hollander JA, Sieber BA, Greenwel P, Shea-Donohue T, Wiley JW. 2021 Workshop: Neurodegenerative Diseases in the Gut-Brain Axis-Parkinson’s Disease. Gastroenterology. 2022 May;162(6):1574-1582. doi: 10.1053/j.gastro.2022.02.004. Epub 2022 Feb 8. PMID: 35149029; PMCID: PMC9038653.) Preclinical work at Plakous has shown the ability to induce oligodendrocyte proliferation in vitro (Footnote: Data on file. Plakous Therapeutics.) and shows promise as potential therapeutic to target the root inflammatory cause for these neurodegenerative diseases.