A novel strategy to increase the therapeutic potency of GBM chemotherapy via altering parenchymal/cerebral spinal fluid clearance rate.

Patients with glioblastoma (GBM) face a poor prognosis with a median survival of less than two years. Escalating the dose of chemotherapy is often impossible due to patient comorbidities; thus, we focused on modulating brain clearance as a mechanism to enhance drug accumulation. Given the recently identified interconnectivity between brain parenchymal fluid and cerebral spinal fluid (CSF), we reasoned enhancing drug concentration in the CSF also increases drug concentration in the parenchyma where a GBM resides.

Elesclomol alleviates Menkes pathology and mortality by escorting Cu to cuproenzymes in mice.

Loss-of-function mutations in the copper (Cu) transporter ATP7A cause Menkes disease. Menkes is an infantile, fatal, hereditary copper-deficiency disorder that is characterized by progressive neurological injury culminating in death, typically by 3 years of age. Severe copper deficiency leads to multiple pathologies, including impaired energy generation caused by cytochrome c oxidase dysfunction in the mitochondria.