THERAPEUTIC BENEFIT OF HYDROGEN PEROXIDE REMOVAL IN FALS

  • Poduslo, Joseph F (PI)

Project: Research project

Project Details

Description

DESCRIPTION: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease of motor neurons primarily of the spinal cord. Dominantly inherited mutations in the gene that encodes human copper/zinc-superoxide dismutase (Cu/Zn-SOS: hSODl), a free radical scavenging enzyme, have been observed in approximately 20-25 percent of patients with FALS Three mutations of hSODl found in FaLS families have caused motor neuronal degeneration similar to that of ALS patients. Free radical-mediated oxidative injury is a critical component in the mechanism of degeneration of motor neurons that results in FALS. The mutated form of hSODl has been suggested to initiate the neuropathological changes associated with FALS by a dominant gain-of-function which results from expression of the mutant protein that confers a neurotoxic property on the enzyme. In this grant application, we summarize the evidence that suggests that hydrogen peroxide-mediated oxidative damage in motor neurons involving hydroxyl radicals and/or nitric oxide is beneficial in the treatment of FALS. We have made the important observation that when catalase is covalently attached to the naturally occurring polyamines, the resultant product has an increased permeability at the blood-brain barrier (*BBB) after systemic administration. We have been able to demonstrate a highly significant increase in survival of FALS mice (G93A) (GlL/+) by 28.9 days after continuous subcutaneous administration with osmotic pumps of polyamine-modified catalase compared to PBX control (p
StatusFinished
Effective start/end date12/15/0011/30/04

Funding

  • National Institutes of Health: $352,750.00
  • National Institutes of Health: $352,750.00
  • National Institutes of Health: $352,750.00

ASJC

  • Medicine(all)
  • Neuroscience(all)

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