small interfering rna targeting protein z dependent protease inhibitor improves hemostasis in von willebrand factor and factor x deficient mice

Original title: “Small interfering RNA targeting protein Z-dependent protease inhibitor improves hemostasis in Von Willebrand factor- and Factor X-deficient mice.”

when to operate after neoadjuvant therapy for borderline resectable pancreatic cancer a critical review and multidimensional decision framework

Original title: “When to Operate After Neoadjuvant Therapy for Borderline Resectable Pancreatic Cancer: A Critical Review and Multidimensional Decision Framework.”

rmnd1 dysfunction causes oxphos deficiency and alters mitoribosomal protein homeostasis in vivo

Original title: “RMND1 dysfunction causes OXPHOS deficiency and alters mitoribosomal protein homeostasis in vivo.”

evaluation of rare mcoln1 variants in a large cohort of synucleinopathies

Original title: “Evaluation of Rare MCOLN1 Variants in a Large Cohort of α-Synucleinopathies.”

international recommendations for child to adult care transition in rare neurological diseases a scoping review and delphi consensus study

Original title: “International recommendations for child to adult care transition in rare neurological diseases: A scoping review and Delphi consensus study.”

outcomes of hepatic artery thrombosis after paediatric liver transplantation hepatic an international multicentre retrospective registry study

Original title: “Outcomes of hepatic artery thrombosis after paediatric liver transplantation (HEPATIC): an international, multicentre, retrospective registry study.”

spleen stiffness to rule out high risk varices in advanced chronic liver disease an individual patient data meta analysis

Original title: “Spleen stiffness to rule out high-risk varices in advanced chronic liver disease: an individual patient data meta-analysis.”

genomic and transcriptomic characterization of angiosarcomas focus on cardiac origin

Original title: “Genomic and Transcriptomic Characterization of Angiosarcomas: Focus on Cardiac Origin.”

pembrolizumab induced sarcoidosis like immune related adverse events a pooled analysis of published cases and report of a novel manifestation involving phosphocalcic metabolism

Original title: “Pembrolizumab-Induced Sarcoidosis-Like Immune-Related Adverse Events: A Pooled Analysis of Published Cases and Report of a Novel Manifestation Involving Phosphocalcic Metabolism.”

intractable hiccups as initial manifestation of achalasia a case report

Original title: “Intractable hiccups as initial manifestation of achalasia: a case report.”

it takes two to tango the intersection of deubiquitinases and m 6 a modification in cancer

Original title: “It takes two to tango: the intersection of deubiquitinases and m(6)A modification in cancer.”

beyond the primary endpoint learning from negative aih trials

Original title: “Beyond the primary endpoint: Learning from "negative" AIH trials.”

cnpy3 variants associated with a recessive developmental and epileptic encephalopathy affect inflammasome and tlr function

Original title: “CNPY3 variants associated with a recessive developmental and epileptic encephalopathy affect inflammasome and TLR function.”

clinical experience with anti interleukin 5 monoclonal antibodies in the treatment of eosinophilic granulomatosis with polyangiitis

Original title: “Clinical experience with anti-interleukin-5 monoclonal antibodies in the treatment of eosinophilic granulomatosis with polyangiitis.”

recurrent primary angiosarcoma of the breast challenges and pitfalls in a case report

Original title: “Recurrent Primary Angiosarcoma of the Breast: Challenges and Pitfalls in a Case Report.”

cinderella no more alpha 1 antitrypsin deficiency associated liver disease steps into the ballroom

Original title: “Cinderella no more: Alpha-1 antitrypsin deficiency-associated liver disease steps into the ballroom.”

An early data check showed the shot didn’t delay tumor progression in a form of head and neck cancer, though BioNTech is holding out hope it might eventually extend survival.

Original title: “BioNTech mRNA cancer immunotherapy misses first objective in key study”

For ultrarare diseases, the path to treatment is especially difficult. There may be only a handful of patients to study, little clinical evidence to guide trials and almost no commercial incentive to develop a therapy. Cousin and her collaborators have since built a comprehensive ADLD program, bringing together an international disease study and a dedicated ADLD Clinical Care Center to better understand the disorder, expand access to expert care and prepare for future treatment trials. "We're already seeing early signs of benefit in some of our neurodegenerative disease programs," Dr. Cousin says. "We're seeing encouraging biological signals that suggest these therapies are working as intended. Mayo Clinic researchers are using individualized approaches to diagnose and treat some of the world's rarest diseases, one patient at a time. Magnified hundreds of times, the cells carry the genetic variant responsible for KCNK9 imprinting syndrome, one of the rarest neurological diseases in the world. Dr. Cousin directs Mayo Clinic's N-of-1 Therapeutics Program, where scientists develop treatment strategies for diseases so rare they may affect only a single person. Margot Cousin, Ph.D., and Han Lee work at a laboratory bench in Mayo Clinic’s N-of-1 Therapeutics Program. The search for a KCNK9 treatment is one part of a much larger effort. Across other ultrarare diseases, Dr. Cousin and her collaborators are applying the same approach, and in some cases, have already carried it from laboratory research to experimental treatment. In 2025, they helped deliver the first custom experimental genetic treatments for Autosomal Dominant Leukodystrophy (ADLD) to a Mayo Clinic patient. The rare, fatal neurological disease slowly destroys the brain's white matter, disrupting the pathways that allow different regions of the brain to communicate.

Original title: “Mayo Clinic advances diagnosis and treatment of rare diseases”