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Prana pharm PBT2
Teppie
Posted: Saturday, January 7, 2012 6:02 PM
Joined: 12/16/2011
Posts: 122


Got this info from a family friend. Anyone else hear about this?

[Someone] asked about how exactly PBT2 works. I give a lay view here. Anybody welcome to correct or add.  Bush [Prana co-founder] had a theory that metals reacting in the brain cause the toxicity that [in turn] causes Alzheimer's.  Someone first suggested using a retired antibiotic with a known attraction for metals called clioquinol. Pre-clinical tests showed it had some effect so they went as far as phase2, when impurities in the clioquinol drug were causing problems that could not be resolved. The trial was stopped and [Prana's stock] price crashed. They had been working on a more effective analog of Clioquinol with better blood brain barrier penetration. That drug is PBT2 and trials were started culminating in a small, but successful ph2 trial with results published mid 2008.|

How it works. The metal attraction of PBT2 is stronger than the attraction the amyloids have, so when in contact with the amyloid plaques it pulls the metals from the amyloid. The plaques, having lost the metal attraction, break down and dissipate.There are proteins on the surface neurons with a stronger attraction to the metals than PBT2. They remove the metals on contact with the drug, as they are now circulating with the drug. That completes the chaperone action. The essential metals that had been trapped in the plaques have been returned to the cells. Note that by removing the metals the plaques have been broken down without a direct attack on the amyloid system, which no one fully understands as the abstract in this thread demonstrates. 

[Other ALZ drugs] BAPI (from JNJ/PFE) and Sola (from LLY) both attack the amyloid system everywhere. By breaking down the amyloid plaques causing the toxicity and cleaning up the synapses of toxic metals, the APP in the synapse is able to function as designed by nature and bring back normal iron levels in neurons, which had been under stress with iron overload and oxidation.
Zinc being returned to neurons binds in the GSK 3 enzyme which had been responsible for breaking down tau. Insulin also binds with GSK3
Copper returning to neurons has various neuroprotective effects and promotes neuron growth and connections. 
Metals also bring glutumate overload under control, which causes a cascading chain reaction type of cell death called excitotoxicity. When one cell dies because of extra glutumate, that chemical is then released to cause the same fate in the next cell.
Put simply, the drug clears up the synapses, breaks down the plaques and replaces essential metals in neurons, giving the brain's repair and balance mechanisms a chance to function again. 
Why not just give zinc and copper in a pill? AEN tried that without success. The cleanup is required first.
The brain has about 20 billion neurons, each one with about 20,000 synapses. To try to chop out various parts of a system we don't fully understand is bound to fail. PBT2 enables the brain to do its own repair.

Above is just as I understand it. Anybody feel free to add or correct.


JAB
Posted: Saturday, January 7, 2012 6:26 PM
Joined: 11/30/2011
Posts: 740


Hi, Teppie.  If you want to get a discussion going, I'd suggest you start your thread on the Clinical Trials forum.

 

This drug is still in early development.  A Phase IIa study has been completed.  Prana recently announced that they're recruiting for a Phase IIb study on Alzheimer's ... in Australia.

 

Prana seems to be targeting Huntington's in the U.S. right now.


Teppie
Posted: Saturday, January 7, 2012 7:03 PM
Joined: 12/16/2011
Posts: 122


Oh! Sorry. Didn't know there was such a discussion group. Thank you.
JAB
Posted: Saturday, January 7, 2012 7:15 PM
Joined: 11/30/2011
Posts: 740


It's a small group ... not all that many of our members are interested in discussing biological targets and mechanisms of action.  You'll get more of a response there.