Gingival and intraventricular haemorrhages are severe newborn diseases causing damage to white matter and neurological dysfunction in surviving newborns who can benefit from gene therapy
Authors: Dowaidar Moataz 
Published: June 2021

Gingival matrix haemorrhage (GMH) and intraventricular haemorrhage (IVH) are major neonatal disorders causing white matter damage (WMI) and neurological impairments in surviving neonates. Preclinical and clinical IVH research has advanced our understanding of the mechanisms driving IVH-induced WMI, including negative effects on oligodendrocyte progenitor cells (OPCs) and blood-generated axons, especially iron and thrombin.Right now, rehabilitation is the sole therapy option. As a result, new treatments must be developed faster to boost these neonates' outcomes. The most promising therapies in IVH124,147,151 infants are blood clot clearance (DRIFT or endoscopic lavage), early intervention (ELVIS), and stem cell transplantation.However, several barriers must be overcome before the findings of this research can be utilized in clinical practice, as both surgical intervention and intraventricular injection have inherent hazards and adverse effects. Brain damage is projected to be decreased by thorough neuro-endoscopic ventricular lavage surgery, and the optimal distribution strategy for stem cells is projected to enhance their therapeutic advantages. Therapy must begin before scarring and permanent damage develop in neonates with IVH, so determining the appropriate treatment window is critical for success.DRIFT clinical research was carried out in newborns with IVH at a median age of 20 days, and some improvements were found, but not as many as expected147.The median age of intervention in ELVIS was 9 days, leading to the lowest ventriculoperitoneal shunt rate observed in neonates with IVH to date and superior results at 2 years111. Nevertheless, prudence is suggested since early surgery may worsen IVH and aggravate damage.Several mechanism-targeted therapies were explored in preclinical animals. Oral or intramuscular thyroxine or celecoxib appear to be the most promising therapy in animal studies, as these drugs were previously granted to humans by the FDA, are straightforward to give and have low adverse-effect profiles. However, iron chelators or anti-thrombin treatment may be poorly tolerated and associated with significant adverse effects.Because the population of people with IVH is so different, a tailored approach to therapy selection may be needed. Blood clot removal, for example, is suitable for babies with grade III IVH but not isolated PVHI. Similarly, regenerative treatments and agents that reduce inflammation and oxidative stress in the brain (such as celecoxib, antioxidants, thyroxine, and stem cells) are likely to be most effective in infants with moderate to severe IVH, while the risk of side effects may limit their use in infants with IVH grade. Other frequent concerns in premature neonates include severe respiratory distress syndrome, low blood pressure, infection, patent ductus arteriosus, and low platelet levels, all of which may delay treatment. Despite these hurdles, feasible therapeutic solutions for neonates with IVH do not seem too far away.