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Pre-Clinical
Study Results For Memory and Cognition Validate Clinical
Development Program
Amarin Corporation plc
(NASDAQ: AMRN) (“Amarin” or
"Company") announced that the results of a pre-clinical
program in memory and cognition using ultra-pure
eicosapentanoic acid (EPA) have been published in the
“Journal of Neurochemistry” (Minogue AM et al
2007 J. Neurochem.
10.1111/j.1471-4159.2007.04848.x) in an article
entitled, “Modulation of amyloid-ß-induced and
age-associated changes in rat hippocampus by
eicosapentaenoic acid.”
The preclinical study was conducted by Professor Marina
Lynch, Department of Physiology, Institute of
Neuroscience, Trinity College, Dublin, and demonstrated
that EPA attenuates the age-related and ß amyloid-induced
impairment of Long Term Potentiation (LTP). 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.
Commenting on the study, Professor Lynch said, “These
findings identify an important potential role for EPA in
modulating ß-amyloid-induced and age-related changes in
the brain and the present findings suggest that the
beneficial effects of EPA are likely to result from its
attenuation of hippocampal IL-1ß concentration, perhaps
as a consequence of its action on expression of PPARg.”
Rick Stewart, Chief Executive Officer of Amarin,
commented, “These findings are very encouraging and
provide the validation to proceed with our clinical
development program using EPA for Age Associated Memory
Impairment and cognition. They are especially important
as the findings reinforce the substantial body of
pre-clinical work already undertaken. We expect to
commence a clinical program in Age Associated Memory
Impairment by year-end.”
About the Role of EPA in Long-Term Potentiation
(LTP), Age Associated Memory Impairment (AAMI) and
Cognition
Aging is associated with impairment in LTP,
resulting in Age Associated Memory Impairment (AAMI) and
cognitive function. This impairment results from
inflammatory and oxidative changes in the hippocampal
area of the brain. In pre-clinical studies, analysis of
the mechanisms underlying the effect of aging on
hippocampal function has focused to a significant extent
on analysis of age-related changes in long-term
potentiation (LTP) in the hippocampus.
Further, these findings support the substantial
preclinical studies previously published in the use of
EPA to promote LTP in aging models.
About Amarin
Amarin is committed to improving the lives of
patients suffering from diseases of the central nervous
system. Our goal is to be a leader in the research,
development and commercialization of novel drugs that
address unmet patient needs.
Amarin’s core development pipeline includes programs
for Parkinson’s disease, Age Associated Memory
Impairment, cognition, epilepsy seizures and other
Central Nervous System (CNS) disorders.
Amarin has its primary stock market listing in the
U.S. on NASDAQ (“AMRN”) and secondary listings in the
U.K. and Ireland on AIM (“AMRN”) and IEX (“H2E”),
respectively.
For press releases and other corporate information,
visit the Amarin website at
http://www.amarincorp.com.
Information on our website does not form part of this
press release.
References
1.
Kavanagh T., Lonergan P. E., and
Lynch M. A. (2004) Eicosapentaenoic acid and gamma-linolenic
acid increase hippocampal concentrations of IL-4 and
IL-10 and abrogate lipopolysaccharide-induced inhibition
of long-term potentiation. Prostaglandins Leukot
Essent Fatty Acids 70, 391-7.
2. Martin D. S., Spencer P., Horrobin
D. F., and Lynch M. A. (2002) Long-term potentiation in
aged rats is restored when the age-related decrease in
polyunsaturated fatty acid concentration is reversed.
Prostaglandins Leukot Essent Fatty Acids 67,
121-30.
3. McGahon B. M., Martin D. S.,
Horrobin D. F., and Lynch M. A. (1999a) Age-related
changes in synaptic function: analysis of the effect of
dietary supplementation with omega-3 fatty acids.
Neuroscience 94, 305-14.
4. McGahon B. M., Murray C. A.,
Horrobin D. F., and Lynch (1999b) Age-related changes in
oxidative mechanisms and LTP are reversed by dietary
manipulation. Neurobiol Aging 20, 643-53.
5. Song C. and Horrobin D. (2004)
Omega-3 fatty acid ethyl-eicosapentaenoate, but not
soybean oil, attenuates memory impairment induced by
central IL-1beta administration. J Lipid Res
45, 1112-21.
6. Song C., Li X., Leonard B. E., and
Horrobin D. F. (2003) Effects of dietary n-3 or n-6
fatty acids on interleukin-1beta-induced anxiety,
stress, and inflammatory responses in rats. J Lipid
Res 44, 1984-91.
7. Song C., Phillips A. G., Leonard
B. E., and Horrobin D. F. (2004) Ethyl-eicosapentaenoic
acid ingestion prevents corticosterone-mediated memory
impairment induced by central administration of
interleukin-1beta in rats. Mol Psychiatry 9,
630-8.
8. Lonergan PE, Martin DSD, Horrobin
DF. and Lynch MA (2004). Neuroprotective actions of
eicosapentaenoic acid on lipopolysaccharide dysfunction
in rat hippocampus. J. Neurochem., 91, 20-29.
9. Lynch AM, Moore M, Craig S,
Lonergan PE, Martin DS and Lynch MA. (2003) Analysis of
IL-1beta -induced cell signaling activation in rat
hippocampus following exposure to gamma irradiation:
protective effect of eicosapentaenoic acid. J Biol Chem.
51, 51075-51084.
10. Martin DS, Lonergan PE, Boland B,
Fogarty MP, Brady M, Horrobin DF, Campbell VA and Lynch
MA (2002) Apoptotic changes in the aged brain are
triggered by interleukin-1 beta -induced activation of
p38 and reversed by treatment with eicosapentaenoic
acid. J. Biol. Chem., 277, 34239-34246.
11. Lonergan PE, Martin DSD, Horrobin
DF and Lynch MA (2002) Neuroprotective effect of
eicosapentanoate in hippocampus of rats exposed to Gamma
irradiation. J. Biol. Chem., 277, 20804-20811.
Contacts:
Amarin +44 (0) 207 907 2442
Rick Stewart Chief Executive Officer
Alan Cooke President and Chief Financial Officer
investor.relations@amarincorp.com
Investors:
Lippert/Heilshorn & Associates, Inc.
Anne Marie Fields +1 212 838 3777
Media:
Powerscourt +44 (0) 207 250 1446
Rory Godson
Broker:
Davy
Fergal Meehan +353 (0) 1 679 6363
Disclosure
Notice:
The information
contained in this document is as of August 1, 2007.
Amarin assumes no obligation to update any
forward-looking statements contained in this document as
a result of new information or future events or
developments. This document contains forward-looking
statements about Amarin's
financial condition, results of operations, business
prospects and products in research that involve
substantial risks and uncertainties. You can identify
these statements by the fact that they use words such as
"will", "anticipate", "estimate", "expect", "project",
"forecast", "intend", "plan", "believe" and other words
and terms of similar meaning in connection with any
discussion of future operating or financial performance
or events. Among the factors that could cause actual
results to differ materially from those described or
projected herein are the following: risks relating to
the Company’s ability to maintain its Nasdaq listing
(including the risk that the Company may not be able to
achieve compliance with the Nasdaq minimum bid price
and/or other continued listing criteria within the
required timeframe or at all and the risk that the
Company may not be able to successfully appeal a Nasdaq
delisting determination); the success of Amarin's research and development activities; decisions by
regulatory authorities regarding whether and when to
approve Amarin's drug applications, as well as their decisions
regarding labeling and other matters that could affect
the commercial potential of Amarin's
products; the speed with which regulatory
authorizations, pricing approvals and product launches
may be achieved; the success with which developed
products may be commercialized; competitive developments
affecting Amarin's
products under development; the effect of possible
domestic and foreign legislation or regulatory action
affecting, among other things, pharmaceutical pricing
and reimbursement, including under Medicaid and Medicare
in the United States, and involuntary approval of
prescription medicines for over-the-counter use; Amarin's
ability to protect its patents and other intellectual
property; claims and concerns that may arise regarding
the safety or efficacy of Amarin's
product candidates; governmental laws and regulations
affecting Amarin's operations, including those affecting taxation;
Amarin's
ability to maintain sufficient cash and other liquid
resources to meet its operating requirements; general
changes in International and US generally accepted
accounting principles; growth in costs and expenses; and
the impact of acquisitions, divestitures and other
unusual items. A further list and description of these
risks, uncertainties and other matters can be found in
Amarin's Form 20-F for the fiscal year ended December 31,
2006, filed with the SEC on March 5 2007, Amarin’s
statutory annual report for the year ended 31 December,
2006 furnished on a Form 6-K to the SEC on May 9, 2007
and in its Reports of Foreign Issuer on Form 6-K
furnished to the SEC.
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