A Timeline

1993 - Synergen synthesizes GDNF

July 1994 - French researchers report Vit D3 increased NGF - GDNF 5x in the lab

Dec 1994 - Amgen buys Synergen

1996 - Amgen trial of monthly injection into brain

Sept 1996 - the French team report Vit D3 increased GDNF 18x in lab

April 1999 - Amgen halts GDNF work

Summer 1999 - NYU researchers show a better way. New Amgen interest

A Phase I trial began in 2001, under the direction of neurosurgeon Steven S. Gill at the University of Bristol Institute of Clinical Neuroscience at Frenchay Hospital in the United Kingdom GDNF was directly infused into the putamen by a pump delivery system. Catheters were inserted into the brain, and GDNF was delivered from pumps implanted in the abdomen. < p> According to researchers, “Within a couple of months, patients were noticing dramatic improvements in their ability to move, and these continued over almost four years of treatment. Even after ceasing medication, the patients’ improvement has been maintained.”(3)

Dr. Michael Hutchinson of New York University related that videotapes of the patients taken before and after treatment were “quite amazing.” One patient initially "took five minutes to walk across a room.” After three months of infusion, “he jumps up and walks back and forth.” (4) After one year in this 2001 Phase 1 safety trial, patients averaged a 40 percent improvement in their symptoms with no serious side effects, reduced dyskinesia, and a 28 percent increase in the amount of dopamine stored in their brains.

In 2002, another Phase I trial was initiated using unilateral direct infusion of GDNF with 10 patients at the University of Kentucky, led by Dr. John Slevin. As in the Bristol trial, researchers and the patients reported positive results.

“… Notably, there appeared to be bilateral improvements, including improved postural stability, which continued through the washout period. All patients with PD also showed evidence of improved affect and fine motor control and speed.”(5) (PD Pipeline)

Dec 2002 - Spanish team report Vit D3 increased GDNF in rats brain striatum when injected intraperitoneally

After the favorable results in the Bristol trial in 2003, Amgen, which had donated the GDNF, stepped in and volunteered to sponsor future phases. The company initiated a multicenter, placebo-controlled trial that included 34 patients, all of whom had a pump-and-catheter delivery system implanted. Half the participants, however, received only saline solution for the first 6 months, and were then switched to GDNF.

Inexplicably, Amgen’s methodology differed from that of the successful phase I trials. The company used larger catheters and a different type of pump (a continuous rather than pulse delivery), and smaller doses of GDNF. Trial participants again reported improvements in their symptoms. After a 6-month analysis of the trial data, however, Amgen in June 2004 reported that improvements in symptoms were not statistically significant, and attributed them to the placebo effect. Even so, Amgen announced that all subjects would be entered in an open label extension study to try to resolve the differing trial results.

On September 1, 2004, however, Amgen abruptly halted the trials and withdrew treatment from participants in all of the study groups. Amgen cited lack of efficacy, and safety concerns, specifically indicating brain autopsies of some of the nonhuman (primate) subjects revealed damage in the cerebellum. It was later learned that the primates had received much higher doses than the human participants. Amgen also announced that GDNF neutralizing antibodies were found in five study participants, and these might lead to a reduction of naturally occurring GDNF in the brain. The Amgen study was initially reported on at the annual meeting of the American Neurological Association conference in October, 2004.

Some of the Phase II trial doctors, including the University of Kentucky team, Dr. Hutchinson of NYU, and Dr. Penn at the University of Chicago, did not agree with Amgen’s conclusions, nor with their safety concerns, and continue to question the statistical tests and methods used in the Phase II trials

The brain autopsy of one of the Bristol study participants, who died of an unrelated heart attack in 2005, revealed that dopamine-containing nerve fibers lost in Parkinson’s disease had sprouted back in the region where GDNF had been infused. Because the GDNF had been infused into one side of the brain only, the effects of the treatment could be assessed by comparing the two sides.

“This is the first neuropathological evidence that infusion of GDNF in humans causes sprouting of dopamine fibers, in association with a reduction in the severity of Parkinson’s,” stated Dr. Seth Love, who studied the tissue. (10)

Read the rest if you can stand it

Feb 2009 - Spanish team reported both protection and repair and GDNF increase in SN of rat model by Vit D3 intraperitoneally

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So, you are a Big Man at one of the biggest Pharms on the planet. You have this chemical that you own the patent for and it does amazing things for, not only PD, but probably other things as well. Things that generate a large part of your cash flow. It will doom some of your competitors but, hey, that's business.

But just as you make your first moves toward the market, one of your researchers breaks the news that the French and Spanish are claiming that you super chemical can probably be produced by simply megadosing with Vit D3.

What the heck are you going to do? You spent all that money to buy Synergen and you have launched research into making it profitable while bragging to the stockholders. If your trials succeed someone is going to point out that the world may not need you in the mix. If youpull the plug you can gain some time.

Then your researcher tells you that the French and Spanish work may threaten a lot more than your PD profits. Sheesh! What's a greedy capitalist to do???

"Is everything a conspiracy? No, just the important stuff."