Neuroimmunophilin
Ligands (NIL)
Summary:
Neuroimmunophilin ligands (NILs) are a novel class of drugs
developed by Guilford that may
have the ability to spark nerve growth and repair.[1] In preclinical
studies, NILs have
crossed the blood-brain barrier and repaired and regenerated damaged nerves
without affecting
normal nerves.[2] In several animal models of Parkinson’s disease,
Guilford's neuroimmunophilin ligands have demonstrated neurotrophic activity. Results
from some of these
studies have been published in The Proceedings of the National Academy of
Sciences and Nature
Medicine.[3] Data suggests that NILs, taken orally, may act to rescue
degenerating neurons,
making it a promising new treatment for Parkinson's disease.[4]
Potential benefits:
- Neuroprotection.
- Nerve growth.
- Nerve repair.
Risks:
Obstacles:
Current research:
Guilford completed a Phase II clinical trial of GPI-1485 sponsored by the
NINDS. Results are expected at the end of 2005
“GPI-1485 This multi-center, randomized, double-blind trial will involve 42
trial centers in
the United States and Canada, and enroll 195 people with PD. The primary
objective of this
neuroprotection trial is to identify agents capable of slowing the
progression of PD. In the
trial, investigators will assess the impact of CoQ10, an antioxidant, and
GPI 1485, a novel
immunophilin compound, on the progression of PD and determine if it is
futile or non-futile to
proceed with further study of these agents.”
“In this study, subjects with early, untreated PD will be equally randomized
into one of the
three study arms: 1) the group that receives active CoQ10 and placebo
instead of GPI-1485; 2)
the group that receives active GPI 1485 and placebo instead of CoQ10; or 3)
the group that
receives placebo instead of CoQ10 and GPI 1485. Subjects will remain on the
blinded study drug
for 12 months.”[5]
An earlier 6-month Phase II study of GPI-1485 in Parkinson’s disease (PD)
and conducted
independently by a collaborator, showed that the drug was safe but did not
show a benefit in
UPDRS motor function, which was the primary endpoint. Guilford reviewed the
data and decided
to initiate a second study because it was clear that the nature and design
of the
collaborator’s (original) trial was such that the placebo group did not
experience a decline
in UPDRS motor scores, and it would not have been possible to detect any
slowing of a decline
of UPDRS in the active group. “Further, there was a trend towards a reversal
in the loss of
dopaminergic nerve terminal density (SPECT images), and an indication of a
drug sparing effect
(symptomatic anti-parkinsonian medications) for the high dose group.”
Subsequently, the NIH
decided to fund a second independent PD study with the GPI 1485 supplied by
Guilford. Results
are expected late in 2005.[6]
[1]
News Release; Wednesday 19 September 2001, 14:39 GMT; Wednesday 19 September
2001; Guilford
Pharmaceuticals;
Guilford regains exclusive worldwide rights to neuroimmunophilin ligand
programme from Amgen
[2] First Clinical Evaluation of Neuroimmunophilin Ligands in Parkinson's
Disease BALTIMORE, July
26, 2001 /PRNewswire --
Guilford Pharmaceuticals Announces Completion Of NIL-A Phase II Clinical
Trial for Parkinson's
Disease
[3]
News Release; Wednesday 19 September 2001, 14:39 GMT; Wednesday 19 September
2001; Guilford
Pharmaceuticals;
Guilford regains exclusive worldwide rights to neuroimmunophilin ligand
programme from Amgen
[4]
Neuroimmunophilin Ligands as Treatment for Neurodegenerative Disorders;
Joseph P. Steiner; Guilford Pharmaceuticals, Baltimore, MD;
CNS Drug Reviews; Vol. 5, Supplement 1, p. 8; © 1999 Neva Press, Branford,
Connecticut
[5]
NINDS Parkinson's Disease
Neuroprotection Trial of CoQ10 and GPI 1485; Clinical Trials.gov
[6]
Neuroimmunophilin Ligands; Stage of Development: Phase II Indication: Parkinson’s Disease and Erectile
Dysfunction;
Last Updated: 05/20/04
|
