Effect of deoxyribonuclease I therapy on free circulating DNA level and gene methylation profile changes in patients with endometriosis: Proof of concept and preliminary data.

ObjectiveEndometriosis is a systemic chronic disease with serious effects on various aspects of female health and wellbeing that has been associated with a significant increase in free circulating DNA (CfDNA) and gene methylation profile changes. Endometriosis is considered a worldwide health problem, affecting approximately 10-12% of women of reproductive age. It is defined as an estrogen-dependent syndrome associated with severe pain and a distinct epigenetic signature. The purpose of this study was to evaluate the effect of deoxyribonuclease (DNase) I therapy on these anomalies.MethodsThis study is a proof-of-concept investigation presenting preliminary data from sixteen patients with endometriosis who were evaluated during infertility consultations. CfDNA extraction, quantification and methylation status tests were performed using commercial kits. DNase I was administered subcutaneously every 2 days for one month, and the pre-treatment and post-treatment CfDNA levels and methylation status, along with the degree of patient discomfort, were compared.ResultsDNase I therapy was associated with a decrease in the overall CfDNA level. Targeted methylation profiles showed exploratory changes in several genes, presented descriptively because no paired inferential reanalysis was performed. Moreover, most patients (15/16) reported a reduction in pain, an improvement in their ability to assume professional activity and fewer sexual function difficulties.ConclusionsThis proof-of-concept study suggests that DNase I therapy may be associated with decreased CfDNA levels and changes in methylation profiles. Patient-reported improvements in pain and quality of life were observed, but they cannot be causally attributed to treatment in the absence of a placebo-controlled design. Further research into the potential use of DNase-based medicine for endometriosis patients involving more participants is warranted.