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
|
