Biotech Values

[Kadaicher1]

Here are three more clues to the Alzheimers puzzle.

1
"The evidence published in Cell shows that the source of beta-amyloid, the beta- amyloid precursor protein (APP), plays a hitherto unknown critical role in exporting iron out of neurons. If APP fails to carry out this role, iron builds up in the neurons contributing to oxidative stress, neurofibrillary tangle formation and ultimately neuronal cell death. Importantly, Prana scientists have demonstrated that synaptic zinc can prevent APP from performing its normal iron transporting role."

http://www.pranabio.com/downloads/Media%20Releases/Media%20Release%202010/Prana%20in%20Cell%203%20Sept%202010.pdf

2

today announced the publication of new data on the ability of PBT2 to repair the damage in an Alzheimer’s affected brain thereby facilitating the restoration of cognition in
Alzheimer’s Disease (AD). The findings help to explain the rapid improvement incognition previously reported in transgenic Alzheimer's mice* and in patients in a Phase
IIa clinical trial with PBT2**. The article published in the science journal PLoS ONE isentitled “Metal Ionophore Treatment Restores Dendritic Spine Density and Synaptic
Protein Levels in a Mouse Model of Alzheimer’s Disease”.

http://www.pranabio.com/downloads/Media%20Releases/Media%20Releases%202011/March%2021%20PBT2%20Directly%20Restores%20Neurons%20Critical%20to%20Cognition.pdf

3

The Journal of Alzheimer's Disease paper reports the results of a post-unblinding analysis of the cognitive data that was not included in the original paper. The objective of the analysis was to see how individual patients who were receiving PBT2 responded compared to the individual patients who only received placebo. Importantly, even placebo patients showed some improvement in the tests because of a ‘learning effect’ of repeated testing. This new analysis has adjusted for this and demonstrated that:
• 81% of patients on the 250mg dose of PBT2 responded better on the Executive Factor NTB score than the best performing patient on placebo.
• 41% of patients on the 250mg dose of PBT2 responded better on the overall Composite NTB score than the best performing patient on placebo (of which Executive Function is one of 2 parts).
Asking the specific question, ‘What is the probability that any patient who showed cognitive improvement was receiving PBT2?’, the paper reports there was a significant probability that:
• Patients who improved in Executive Function were probably receiving 250mg of PBT2 (p=1.3 x 10-9)
• Patients who improved their Composite NTB were probably receiving 250mg of PBT2(p=.0007)
Improvement in ADAS-Cog, a measure of memory and cognition, almost achieved a statistically significant level in the 12 week trial. Patients who improved their ADAS-Cog score were probably receiving 250mg of PBT2 (p=.056).]

http://www.pranabio.com/downloads/Media%20Releases/Media%20Release%202010/New%20Analysis%20JAD%2019%20April%202010.pdf

That trial was done in Australia and Sweden. 75pts and unfortunatly only 29 on 250mg. Trial doc made a mistake in putting patients in groups. When the numbers were crunched as individuals the very different picture above emerged. The reason they were able to demonstrate efficacy in such a short trial in mild alzheimers patients was that in the 250mg arm cognition improved in the more sensitive executive function measures.

And some independent comment on the APP and amyloid role from Rudy Castellani, Paula Moreira, Akihiko Nunomura, George Perry, ARF Advisor (Disclosure), The late Mark A. Smith (Disclosure), Xiongwei Zhu
"It is not surprising that AßPP is a critical marker of axonal injury (Cochran et al., 1991) and repair, as both ceruloplasmin and ferritin play similar roles. When seen together with the antioxidant role of Aß through copper chelation (Hayashi et al., 2007), the reparative power of the amyloid pathway cannot be questioned (Rottkamp et al., 2001; Castellani et al., 2009). "

http://www.alzforum.org/new/detail.asp?id=2660

I know no one believes the metal theory, but you have to admit the evidence is building.