Debates over orphan drug pricing: a meta-narrative literature review

Hanchard, M.S. Debates over orphan drug pricing: a meta-narrative literature review. Orphanet J Rare Dis 20, 107 (2025). doi:10.1186/s13023-025-03634-2 

The review finds a sustained call for reform, centred on welfare economics and resource allocation, where current incentives and regulations are held to be insufficient. Overall, the article recommends that regulators look to alternative models of innovation steeped in social science thinking to modify reviewing appraisal, coverage, and reimbursement processes for orphan drugs. Also, that greater patient inclusion and transparency would help include a wider range of intangible social factors that rare disease patients face in accessing high priced orphan drugs.

Brain microvascular endothelial cells differentiated from a Friedreich's Ataxia patient iPSC are deficient in tight junction protein expression and paracellularly permeable

Brain microvascular endothelial cells differentiated from a Friedreich's Ataxia patient iPSC are deficient in tight junction protein expression and paracellularly permeable. Front. Mol. Neurosci. Sec. Brain Disease Mechanisms, Volume 18 - 2025 | doi: 10.3389/fnmol.2025.1511388 

These data show that decreased barrier integrity is a pathophysiologic phenotype of FA brain microvascular endothelial cells. Clinically, this may be a targetable pathway to abrogate brain iron accumulation, neuroinflammation, and neurodegeneration profiles of FA. Additionally, investigation into other barrier systems, such as the blood-nerve barrier, blood-CSF barrier, or cardiac vasculature may inform on extra-neural symptoms experienced by the FA patient.