More is being done with neuroimmunoligands.
Clinical trials still iffy.
.......................................................
Eur J Neurosci 2001 Mar;13(6):1085-1092
Immunophilin ligands can prevent progressive dopaminergic degeneration in animal
models of Parkinson's disease.
Costantini LC, Cole D, Isacson O.
Neuroregeneration Laboratory, 115 Mill Street, Harvard Medical School/McLean
Hospital, Belmont, MA 02178, USA and Department of Neurology and Psychiatry,
Massachusetts General Hospital/McLean Hospital, Belmont, MA, USA; Vertex
Pharmaceuticals, Inc; Cambridge, MA, USA.
Slowing or halting the progressive dopaminergic (DA) degeneration in Parkinson's
disease (PD) would delay the onset and development of motor symptoms, prolong
the efficacy of pharmacotherapies and decrease drug-induced side-effects. We
tested the potential of two orally administered novel immunophilin ligands to
protect against DA degeneration in two animal models of PD. First, in an MPTP
(N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) mouse model, we compared an
immunophilin ligand (V-10,367) documented to bind the immunophilin FKBP12 with
V-13,661, which does not bind FKBP12. Both molecules could prevent the loss of
striatal DA innervation in a dose-dependent fashion during 10 days of oral
administration. Second, to determine whether an immunophilin ligand can protect
against progressive and slow DA degeneration typical of PD, an intrastriatal
6-hydroxydopamine-infusion rat model was utilized. Oral treatment with the
FKBP12-binding immunophilin ligand began on the day of lesion and continued for
21 days. At this time point, post mortem analyses revealed that the treatment
had prevented the progressive loss of DA innervation within the striatum and
loss of DA neurons within the substantia nigra, related to functional
outcome as
measured by rotational behaviour. Notably, DA fibres extending into the
area of
striatal DA denervation were observed only in rats treated with the immunophilin
ligand, indicating neuroprotection or sprouting of spared DA fibres. This
is the
first demonstration that immunophilin ligands can prevent a slow and progressive
DA axonal degeneration and neuronal death in vivo. The effects of orally
administered structurally related immunophilin ligands in acute and progressive
models of DA degeneration are consistent with the idea that these compounds may
have therapeutic value in PD.
PMID: 11285005 [PubMed - as supplied by publisher]
.......................................................
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
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