[CarolynS]

Ceregene, Inc. Reports New Findings Regarding How Parkinson's Brains Respond to Neurotrophic Factors

See Clinical Trials board: Neuturin; Ceregene Reports New Findings

[paula_w]

The only new anything I can see is the patient that has been followed for 5 years still producing neurturin. To have been studied for 5 years he has to be in the original study before modifications.

The two autopsies are old news and formed the basis for the new trials taking place now. They modified the target and the dosages based on those autopsies of two people who died from the original study.

Corrrect me if i'm wrong - otherwise this article is completely misleading IMHO.

[RLSmi]

What is new in the recent publication by Bartus et al, is their discovery that the movement behavior of CERE-120 in PD patients/subject's brains was different from that in the MPTP-treated monkey brains.

In both the PD patients and MPTP- treated monkeys the therapeutic viral agent was targeted only into the striatum and putamen. These areas contain the axons and nerve terminals, respectively, of the dopaminergic neurons which have their cell bodies in the substantia nigra.

When injecting the CERE-120 into both monkeys and PD patients,they avoided the substantia nigra. This was because, in previous animal (rat) studies by other researchers with GDNF gene therapy, injection of the agent into the substantia nigra failed to restore function, wereas targeting just the putamen and striatum was sufficient to rescue the entire nerve tracts, including the substantia nigra. This was attributed to "retrograde transport" (backing up) of the neurotrophic agent into the nigral cell bodies.

What Bartus et al discovered in this recent work was that the neurturin produced by the injected CERE-120 agent was present and active in the substantia nigra of the monkeys but not in that same critical region of the PD patients. They concluded that this difference was due to deficient axonal retrograde transport of CERE-120 in advanced PD, and proposed that ...future efforts using neurotrophic-factors to treat neurodegenerative diseases will need to target both the terminal fields and the cell bodies of degenerating neurons to assure maximal benefit is achieved.
Bartus, R.I., et al, 2011 Movement Disorders, Vol 26, No. 1, 27-36.

Robert

[paula_w]

Originally Posted by RLSmi

What is new in the recent publication by Bartus et al, is their discovery that the movement behavior of CERE-120 in PD patients/subject's brains was different from that in the MPTP-treated monkey brains.

In both the PD patients and MPTP- treated monkeys the therapeutic viral agent was targeted only into the striatum and putamen. These areas contain the axons and nerve terminals, respectively, of the dopaminergic neurons which have their cell bodies in the substantia nigra.

When injecting the CERE-120 into both monkeys and PD patients,they avoided the substantia nigra. This was because, in previous animal (rat) studies by other researchers with GDNF gene therapy, injection of the agent into the substantia nigra failed to restore function, wereas targeting just the putamen and striatum was sufficient to rescue the entire nerve tracts, including the substantia nigra. This was attributed to "retrograde transport" (backing up) of the neurotrophic agent into the nigral cell bodies.

What Bartus et al discovered in this recent work was that the neurturin produced by the injected CERE-120 agent was present and active in the substantia nigra of the monkeys but not in that same critical region of the PD patients. They concluded that this difference was due to deficient axonal retrograde transport of CERE-120 in advanced PD, and proposed that ...future efforts using neurotrophic-factors to treat neurodegenerative diseases will need to target both the terminal fields and the cell bodies of degenerating neurons to assure maximal benefit is achieved.
Bartus, R.I., et al, 2011 Movement Disorders, Vol 26, No. 1, 27-36.

Robert

forget about it!