PRODUCTS

PRODUCTS

AMR101 for AAMI

INTRODUCTION

AAMI is a recognized syndrome relating to memory changes associated with normal aging. AAMI is a common condition in individuals over 50 years of age. In the United States, it is estimated that approximately 40% of people aged 65 and above, or 16 million, have AAMI. It is characterized by gradual memory impairment (subjective memory decline and objective memory loss) with the absence of dementia. Individuals with AAMI have been shown to have a three-fold greater risk for development of dementia than individuals who do not meet AAMI criteria. There is currently no prescription drug therapy for AAMI.

Amarin is currently conducting a Phase IIa trial in Age Associated Memory Impairment (AAMI) with AMR101 (ultra pure ethyl-EPA). The trial - randomized, double-blinded, and placebo-controlled - will enroll 96 patient volunteers with AAMI. Three dose strengths of AMR101 (1g, 2g, 4g) will be tested for efficacy versus placebo. Efficacy will be assessed by a computerised battery of cognition tests designed by Cognitive Drug Research (CDR) Ltd, a world leader in the provision of innovative cognitive function assessment technology. Initial results from the study are anticipated in the second half of 2008.


DEVELOPMENT TO DATE

In a preclinical program conducted by the Institute of Neuroscience at Trinity College, Dublin, Ireland, which looked at the impact on hippocampal IL-IB, long term potentiation (LTP) and synaptic efficacy, it was shown that EPA attenuates the age-related and ß amyloid-induced impairment of LTP1. LTP is a phenomenon considered an important marker of the integrity of neural processes involved in memory and cognition. This mechanism was identified by Professor Eric Kandel as fundamental in mediating memory and cognition and, consequently, LTP is considered a major mechanism by which the brain learns and maintains memories.

The study confirmed that EPA reduced concentrations of the pro-inflammatory interleukin 1ß (IL-ß), and phosphorylation of the stress-activated protein kinase, c-jun N-terminal kinase (JNK). These factors are associated with inhibition of LTP thus potentially impair memory and cognition.


REFERENCES
  1. Minogue et al - Journal of Neurochemistry 2007;10.1111/j.1471-4159.2007.04848.x - “Modulation of Amyloid-ß-induced and Age-associated Changes in Rat Hippocampus by Eicosapentaenoic Acid”
FURTHER READING
  • Kavanagh et al - Prostaglandins Leukot Essent Fatty Acids 2004;70:391-7 - “Eicosapentaenoic Acid and Gamma-linolenic Acid Increase Hippocampal Concentrations of IL-4 and IL-10 and Abrogate Lipopolysaccharide-induced Inhibition of Long-term Potentiation” 
  • Martin et al - Prostaglandins Leukot Essent Fatty Acids 2002;67: 121-30 - “Long-term Potentiation in Aged Rats is Restored when the Age-related Decrease in Polyunsaturated Fatty Acid Concentration is Reversed”
  • McGahon et al - Neuroscience 1999;94: 305-14 – “Age-Related Changes in Synaptic Function: Analysis of the Effect of Dietary Supplementation with Omega-3 Fatty Acids”
  • McGahon et al - Neurobiol Aging 1999;20:643-53 – “Age-Related Changes in Oxidative Mechanisms and LTP are Reversed by Dietary Manipulation”
  • Song et al - J Lipid Res 2004;45: 1112-21 – “Omega-3 Fatty Acid Ethyl-Eicosapentaenoate, but not Soybean Oil, Attenuates Memory Impairment Induced by Central IL-1beta Administration”
  • Song et al - J Lipid Res 2003;44: 1984-91 – “Effects of dietary n-3 or n-6 fatty acids on interleukin-1beta-induced anxiety, stress, and inflammatory responses in rats”
  • Song et al - Mol Psychiatry 2004;9: 630-8. – “Ethyl-Eicosapentaenoic Acid Ingestion Prevents Corticosterone-Mediated Memory Impairment Induced by Central Administration of Interleukin-1beta In Rats”
  • Lonergan et al - J. Neurochem 2004;91: 20-29 –“Neuroprotective Actions of Eicosapentaenoic Acid on Lipopolysaccharide Dysfunction in Rat Hippocampus”
  • Lynch et al - J Biol Chem. 2003;51:51075-51084 – “Analysis Of IL-1beta-Induced Cell Signaling Activation in Rat Hippocampus Following Exposure to Gamma Irradiation: Protective Effect Of Eicosapentaenoic Acid”
  • Martin et al – J. Biol. Chem 2002;277:34239-34246 - “Apoptotic Changes in the Aged Brain are Triggered by Interleukin-1 Beta-Induced Activation of P38 and Reversed by Treatment with Eicosapentaenoic Acid”
  • Lonergan et al - J. Biol. Chem 2002;277:20804-20811. – “Neuroprotective Effect of Eicosapentanoate in Hippocampus of Rats Exposed to Gamma Irradiation”

This page was last updated on May 30, 2008