AI Article Synopsis

  • Menkes disease is a serious genetic disorder linked to copper metabolism, caused by mutations in the ATP7A gene, leading to a deficiency in dopamine-beta-hydroxylase.
  • A new diagnostic test was created to detect Menkes disease early, allowing for timely copper treatment that has improved survival rates and neurodevelopment outcomes for affected patients.
  • Researchers are exploring gene therapy using adeno-associated viruses in a mouse model to improve brain function and survival in patients with non-responsive ATP7A mutations, with cerebrospinal fluid catechols as potential indicators for therapy effectiveness.

Article Abstract

Menkes disease is a lethal X-linked recessive disorder of copper metabolism caused by mutations in ATP7A, a copper-transporting ATPase with diverse and important biological functions. Partial deficiency of dopamine-beta-hydroxylase is a biochemical hallmark of this illness due to the normal role of ATP7A in delivery of copper as an enzymatic cofactor. We exploited this fact to develop a diagnostic test for Menkes disease, which proved highly sensitive and specific. The assay has enabled early identification of affected patients, leading to enhanced survival and improved neurodevelopment after early copper treatment, including some completely normal outcomes. In preclinical efforts to develop improved therapies for patients with non-copper-responsive ATP7A mutations, we used brain-directed adeno-associated viral gene therapy to rescue a murine model of the disease. Statistically significant improvement in brain catechol ratios correlated with enhanced survival, and cerebrospinal fluid catechols represent candidate surrogate markers of treatment effect in a future gene therapy clinical trial.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6421562PMC
http://dx.doi.org/10.1016/B978-0-12-411512-5.00011-7DOI Listing

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