Research Results of Guilford`s
Neuroimmunophilin Ligand
Program Published in Nature
Medicine Paper Describes
Research by Guilford
Pharmaceuticals and Johns
Hopkins <>
BALTIMORE, April 1 /PRNewswire/ via Individual Inc. -- Guilford
Pharmaceuticals Inc. (Nasdaq: GLFD) today announced the
publication of research results from the Company's
neuroimmunophilin small molecule neurotrophic agent program in
today's issue of Nature Medicine, April 1997, Volume 3, Number 4,
pp. 421-428. The paper describes some of the initial research
conducted and discoveries made in the area by Guilford
Pharmaceuticals and Johns Hopkins University which led to the
separation of the immunosuppressant and neurotrophic activity
of immunophilin ligands.
Immunosuppressive drugs such as cyclosporin A and FK-506 are
known to bind to intracellular proteins called immunophilins.
Scientists at Johns Hopkins previously discovered that
immunophilins are enriched 10-50 fold more in the brain than in
immune tissue. The current paper, authored by scientists from
both Guilford Pharmaceuticals and Johns Hopkins University,
describes some of the initial cell culture and animal experiments
conducted with both immunosuppressive compounds such as
FK-506, cyclosporin A, and rapamycin, as well as
non-immunosuppressive derivatives of those compounds.
These experiments demonstrated that non-immunosuppressive
analogs of immunosuppressive drugs promote neurite outgrowth
in cell culture experiments in both PC12 cells as well as sensory
neuronal cultures of chick dorsal root ganglia, with potencies
comparable to their immunosuppressive homologues. It was
noted that the neurotrophic potencies of immunophilin ligands
parallel their potencies to bind to the immunophilins FKBP-12 or
cyclophilin. A further finding of the research was that binding to
calcineurin, the required target for immunosuppressive activity, is
not required for neurotrophic activity, since
non-immunosuppressive compounds which do not inhibit
calcineurin, are also neurotrophic.
These data also suggested that it would be possible to design
compounds which selectively interacted with FKBP-12 and
produced a neurotrophic effect, but lacked the
immunosuppression associated with immunosuppressive agents.
Further experiments in whole animals with both
immunosuppressive and non- immunosuppressive immunophilin
ligands showed that non-immunosuppressive immunophilin
ligands are neurotrophic in intact animals. In rats whose sciatic
nerves were crushed, both immunosuppressive and
non-immunosuppressive immunophilin ligands enhanced both
functional and morphologic recovery of the damaged nerves.
Furthermore, the compounds were also able to regenerate the
myelin sheath over the nerves, a characteristic critical to nerve
re-growth and recovery of function.
Guilford scientists, utilizing structure-based drug design and
combinatorial chemistry, have expanded on these original
findings, and have synthesized hundreds of proprietary small
molecule neuroimmunophilin ligands in several chemical series
which possess neurotrophic activity but are devoid of
immunosuppressive properties.
"This publication describes some of the original discoveries in
this important new field first made by Johns Hopkins scientists,
which laid the groundwork for Guilford's program in this area.
These findings are particularly notable in that they demonstrate
both physiological and behavioral recovery following oral
administration of small molecule neuroimmunophilin ligands in
animal models of neuronal degeneration. Our discoveries may
represent an important new approach to the treatment of a wide
variety of neurodegenerative disorders," commented Dr. Solomon
H. Snyder, Director of the Department of Neuroscience at The
Johns Hopkins University School of Medicine.
Other results from Guilford's neuroimmunophilin research program
were published last month in the Proceedings of the National
Academy of Sciences (U.S.A.), Volume 94, number 5, pp.
2019-2024, 1997. Last week, Guilford also announced that it had
received U.S. Patent Number 5,614,547 from the U.S. Patent and
Trademark Office, relating to compositions and neurotrophic uses
of immunophilin ligands.
Guilford Pharmaceuticals Inc. is a biopharmaceutical company
engaged in the development of polymer-based therapeutics for
cancer, and novel products for the diagnosis and treatment of
neurological diseases, including Parkinson's disease, Alzheimer's
disease, stroke, severe head trauma, spinal cord injuries, multiple
sclerosis, peripheral neuropathies, and cocaine addiction.
SOURCE Guilford Pharmaceuticals Inc.
/CONTACT: Angela Webber of Guilford Pharmaceuticals,
410-631-6449; for media, Brad Miles of B.M.C. or for investors,
Jonathan Fassberg of The Trout Group, 212-477-9007/ (GLFD)
