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Old 08-23-2013, 08:51 AM
soccertese soccertese is offline
Magnate
 
Join Date: Nov 2007
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soccertese soccertese is offline
Magnate
 
Join Date: Nov 2007
Posts: 2,531
15 yr Member
Default on Palfreman’s Blog, comment on nigrostriatal pathology and gene therapy trials

excerpt, he does go into more detail in full opinion piece:
14 AUGUST 2013

Now For The Bad News

The Holy Grail of PD research is to find a disease-modifying therapy. If one could deliver neurotrophic factors to the putamen, for example, and rescue ailing dopamine neurons, it might change the trajectory of the disease. Unfortunately, most recent efforts have ended in failure. Setbacks include Amgen’s negative glial-derived neurotrophic factor (GDNF) infusion trials, Ceregene’s two failed Neurturin gene therapy trials (in 2008 and 2013) and Phytopharm’s 2013 unsuccessful trial of Cogane, an oral medicine designed to stimulate growth factor production. Some scientists like neurosurgeon Steven Gill argue that this neurotrophic strategy may eventually work, when researchers figure out how to deliver the right dose on the right schedule to the correct area of the brain. Others argue the failures have a simpler explanation — there’s nothing left to rescue; that trial patients’ nigrostriatal damage is too advanced to reverse.


This bleak conclusion is suggested in a landmark paper by Jeff Kordower et al., which investigated nigrostriatal pathology in 28 post mortem Parkinsonian brains and compared them with 9 controls. Since the PD patients survived for varying lengths after diagnosis (from 1-27 years), Kordower et al. set out to estimate dopamine loss in the substantia nigra pars compacta and putamen at different stages of the disease.


Using stains for two proteins normally active at dopaminergic terminals—tyrosine hydroxylase (the enzyme that converts tyrosine into L-dopa) and dopamine transporter (a protein that mediates dopamine reuptake) — Kordower et al. searched for dopaminergic damage. The team found plenty. At diagnosis, the substantia nigra pars compacta and dorsal putamen had lost respectively 50-90% and 50% of their functional markers. But as the enclosed figure graphically shows, the news gets much worse. By 4 years post diagnosis, the tyrosine hydroxylase stain in the dorsal putamen was completely gone. The team found an almost identical picture of total loss over 4-5 years in the dopamine transporter stains.

http://www.journalofparkinsonsdiseas...mans_Blog.html

so stem cells and/or fetal transplants for advanced pd'ers? just my layman's take.
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