PMID:Immunophilin Ligand GPI 1046 in MPTP-Treated Monkeys

[Raymond Strand <strandra@xxxxxxxxxxxxx>]

Greetings list:

Here is the latest on GPI 1046.

It must have been put on the fast track--
and they are now just getting around to the monkey studies.
It will the interesting to see how the human studies have done.

Ray

 .......................................................
Exp Neurol 2001 Mar;168(1):171-182

Systemic Administration of the Immunophilin Ligand GPI 1046 in MPTP-Treated
Monkeys.

Emborg ME, Shin P, Roitberg B, Sramek JG, Chu Y, Stebbins GT, Hamilton JS,
Suzdak PD, Steiner JP, Kordower JH

Research Center for Brain Repair, Rush Presbyterian-St. Luke's Medical Center,
Chicago, Illinois, 60612

[Record supplied by publisher]

Systemic administration of immunophilin ligands provides trophic influences to
dopaminergic neurons in rodent models of Parkinson's disease (PD) resulting in
the initiation of clinical trials in patients with Parkinson's disease. We
believe that prior to clinical trials, novel therapeutic strategies should show
safety and efficacy in nonhuman models of PD. The present study assessed whether
oral administration of the immunophilin 3-(3-pyridyl)-1-propyl
(2S)-1-(3,3-dimethyl-1,2-dioxopentyl)-2-pyrrollidinecarboxylate (GPI 1046) could
prevent the structural and functional consequences of
n-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration in nonhuman
primates. Twenty-five rhesus monkeys received daily oral administration of
vehicle (n = 5) or one of four doses of GPI 1046 (0.3 mg/kg, n = 5; 1.0
mg/kg, n
= 5; 3.0 mg/kg, n = 5; 10.0 mg/kg, n = 5). Two weeks after starting the drug
treatment, all monkeys received a unilateral intracarotid injection of MPTP-HCl
(3 mg). Daily drug administration continue for 6 weeks postlesion after which
time the monkeys were sacrificed. Monkeys were assessed for performance on a
hand reach task, general activity, and clinical dysfunction based on a clinical
rating scale. All groups of monkeys displayed similar deficits on each
behavioral measure as well as similar losses of tyrosine hydroxylase
(TH)-immunoreactive (ir) nigral neurons, TH-mRNA, and TH-ir striatal optical
density indicating that in general treatment failed to have neuroprotective
effects. Copyright 2001 Academic Press.

PMID: 11170732
 .......................................................

                                 Ray Strand
                             Prairie Sky Design
 -----------------(   on  the Edge of the Prairie Abyss  )---------------
                          when  the  sky  is  clear
                            the ground is visible

                     49/dx PD 2 yrs/40? onset/retired