Potential new complication in drug therapy development for amyotrophic lateral sclerosis

ABSTRACT

Introduction: 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.

KEYWORDS:

• ALS
• animal models
• blood-CNS barrier
• clinical trials
• drug therapy
• patients

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This review was supported by the Center of Excellence for Aging and Brain Repair, Department of Neurosurgery and Brain Repair at the University of South Florida. S Garbuzova-Davis is funded by National Institutes of Health [1R01 NS090962-01].