http://biz.yahoo.com/prnews/980925/md_guilfor_1.html
Company Press Release
Data Presented on Two Guilford Pharmaceuticals Neuroscience Programs at
Acute Neuronal Injury Conference
Pre-Clinical Data Presented on PARP Inhibitors and
FKBP-Neuroimmunophilin
Ligands
BALTIMORE, Sept. 25, 1998 /PRNewswire/ -- Guilford Pharmaceuticals
(Nasdaq: GLFD - news) announced today that new data on two lead
neuroscience programs were presented at the ``Acute Neuronal Injury: New
Therapeutic Opportunities'' meeting sponsored by the Cambridge
Healthtech Institute in Las Vegas.
Dr. Craig R. Smith, President and CEO of Guilford, commented, ``We are
extremely pleased to reveal what we consider to be exciting new data on
two promising neuroscience programs. For the first time, Guilford
presented data which suggest the promising clinical and commercial
potential of PARP inhibition with our prototype compound, GPI 6150. In
addition, Amgen presented new efficacy and pharmacokinetic data on the
companies' lead FKBP-neuroimmunophilin ligand, ''NIL-A,`` which suggest
significantly superior properties as compared to
first generation prototype compounds.''
Neuroprotectant Program
Poly (ADP-ribose) polymerase (PARP) is an enzyme found in the nucleus of
cells. Stroke, or other conditions which result in diminished blood
flow, or ischemia, cause DNA damage which in turn activates PARP. The
over-activation of PARP during ischemic events causes a depletion of
cellular energy which ultimately results in cell death. Scientists at
Guilford and their academic collaborators have theorized that the
inhibition of PARP may represent a novel mechanism to prevent
degeneration-induced cell death. Accordingly, Guilford scientists have
developed, and are studying, several series of potent small molecule
PARP inhibitors as neuroprotective agents against stroke and other
ischemic disorders including, myocardial ischemia, diabetes, septic
shock, Parkinson's disease, Alzheimer's disease, head trauma and spinal
cord injuries.
During the conference, Dr. Jie Zhang, a senior scientist at Guilford,
presented animal data suggesting the potential role of PARP inhibitors
in treating cerebral vascular stroke and myocardial infarction. Dr.
Zhang's data provide
evidence that the activation of PARP plays a pivotal role in mediating
ischemic injuries. In animal models of cerebral focal ischemia,
Guilford's prototype PARP inhibitor, GPI 6150, reduced overall cerebral
infarct damage by approximately 85%. In a separate experiment
investigating the cardioprotective effects of GPI 6150 in a model of
myocardial ischemia, or heart attack, a 47% reduction in myocardial
infarct size was observed.
Neurotrophic Program
FKBP-neuroimmunophilin ligands are novel, orally-active, small molecule
neurotrophic compounds that cross the blood-brain barrier and which have
the potential to promote nerve regeneration and repair. Pre-clinical
research
by Guilford and Amgen scientists has demonstrated that
FKBP-neuroimmunophilin compounds can protect certain dopamine neurons
and stimulate regeneration of neurological pathways, suggesting that
this class of compounds may have application in the treatment of a
variety of neurodegenerative disorders including, Parkinson's disease,
Alzheimer's disease, stroke, multiple sclerosis and peripheral
neuropathies.
In August 1997, Guilford entered into a major collaboration with Amgen
Inc. [Nasdaq:AMGN - news] in which Amgen was granted the rights to
develop, manufacture and sell products based upon Guilford's proprietary
FKBP-neuroimmunophilins ligands. Over the past several months Guilford
and Amgen have made considerable progress optimizing their lead second
generation FKBP-neuroimmunophilin compound, NIL-A, which is being
developed initially for the treatment of Parkinson's disease.
Data presented by Amgen support the potential use of the
FKBP-neuroimmunophilin ligands as a disease modifying agent in the
treatment of Parkinson's disease. Efficacy and pharmacokinetic studies
of NIL-A have demonstrated that it possesses approximately 50% oral
bioavailability and has 25 times greater potency than GPI 1046,
Guilford's first generation, prototype FKBP-neuroimmunophilin ligand.
Moreover, pharmacokinetic studies of NIL-A in small animals and primates
evidenced superior half life and absorption profiles versus GPI 1046.
These new data demonstrate a favorable pre-clinical profile of NIL-A,
and provide additional support for the selection of NIL-A as the
companies' lead FKBP-neuroimmunophilin clinical compound.
SOURCE: Guilford Pharmaceuticals, Inc.
Copyright © 1998 PRNewswire.
--
Judith Richards, London, Ontario, Canada
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