title: Potential new complication in drug therapy development for amyotrophic lateral sclerosis.
abstract: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by motor neuron degeneration in the brain and spinal cord. Treatment development for ALS is complicated by complex underlying disease factors. Areas covered: Numerous tested drug compounds have shown no benefits in ALS patients, although effective in animal models. Discrepant results of pre-clinical animal studies and clinical trials for ALS have primarily been attributed to limitations of ALS animal models for drug-screening studies and methodological inconsistencies in human trials. Current status of pre-clinical and clinical trials in ALS is summarized. Specific blood-CNS barrier damage in ALS patients, as a novel potential reason for the clinical failures in drug therapies, is discussed. Expert commentary: Pathological perivascular collagen IV accumulation, one unique characteristic of barrier damage in ALS patients, could be hindering transport of therapeutics to the CNS. Restoration of B-CNS-B integrity would foster delivery of therapeutics to the CNS.
authors.affiliation: a Center of Excellence for Aging & Brain Repair , University of South Florida, Morsani College of Medicine , Tampa , FL , USA.|b Department of Neurosurgery and Brain Repair , University of South Florida, Morsani College of Medicine , Tampa , FL , USA.|c Department of Molecular Pharmacology and Physiology , University of South Florida, Morsani College of Medicine , Tampa , FL , USA.|d Department of Pathology and Cell Biology , University of South Florida, Morsani College of Medicine , Tampa , FL , USA.
authors.forename: Svitlana
authors.initials: S
authors.lastname: Garbuzova-Davis
authors.affiliation: e Department of Neurology , University of South Florida, Morsani College of Medicine , Tampa , FL , USA.
authors.forename: Avery
authors.initials: A
authors.lastname: Thomson
authors.affiliation: a Center of Excellence for Aging & Brain Repair , University of South Florida, Morsani College of Medicine , Tampa , FL , USA.
authors.forename: Crupa
authors.initials: C
authors.lastname: Kurien
authors.affiliation: a Center of Excellence for Aging & Brain Repair , University of South Florida, Morsani College of Medicine , Tampa , FL , USA.|b Department of Neurosurgery and Brain Repair , University of South Florida, Morsani College of Medicine , Tampa , FL , USA.
authors.forename: R Douglas
authors.initials: RD
authors.lastname: Shytle
authors.affiliation: a Center of Excellence for Aging & Brain Repair , University of South Florida, Morsani College of Medicine , Tampa , FL , USA.|b Department of Neurosurgery and Brain Repair , University of South Florida, Morsani College of Medicine , Tampa , FL , USA.|d Department of Pathology and Cell Biology , University of South Florida, Morsani College of Medicine , Tampa , FL , USA.|f Department of Psychiatry , University of South Florida, Morsani College of Medicine , Tampa , FL , USA.
authors.forename: Paul R
authors.initials: PR
authors.lastname: Sanberg
mesh_terms: D000690:Amyotrophic Lateral Sclerosis; D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D004364:Pharmaceutical Preparations
chemical_list: D004364:Pharmaceutical Preparations
keywords: ALS; animal models; blood-CNS barrier; clinical trials; drug therapy; patients