Big post Mutai! Espicially the part that read "sig

Big post Mutai! Espicially the part that read "significant MANF news."

Here is Brick's sticky:

MANF
• Retinitis Pigmentosa: functional genetic mouse model (1H-14)
• Parkinson’s disease: CED delivery data w/Renishaw (1H-14)
• Preliminary systemic toxicology (PK/PD relationship) (1H-14)
• Wolfram Syndrome enablement (Diabetes)

Read More: http://investorshangout.com/post/view?id=1551...z35r2ILGdC

If this is CED data from Renishaw it will be huge! (Bigger than Lmypro news!). I went back to the company archives to refresh my memory as to where we're at with MANF and thought I'd post them here if you are interested and for your convenience. Otherwise ignore the rest of this post. It is excessively long and too thick for me to thoroughly comprehend and explain. I underlined the most pertinent parts to which I referred. I have also edited the 4 PRs so go to the company archives if you want the complete article. This could be the start of a parade of PRs' to pop the pps before up listing.

PLEASE FEEL FREE TO CRITICIZE, CRITIQUE AND CORRECT THIS POST!

If this is the CED from data renishaw this will be huge. One of the reasons MJFF rejected our grant request was due to a dispute over whether the technique of delivery skewed the test results. And that's why we turned to Renishaw. They have developed techniques of catheter delivery that will deliver and diffuse MANF in a more effective manner. They also rejected it because of mathematical insignificance (only 12 rats in the study). Which also did not allow more thorough simultaneous analysis.

This is a link about CED delivery.
http://www.medscape.com/viewarticle/712531

If it is Renishaw data I would expect the MJFF to reconsider our grant application and eventually approve it. Other MANF news is at the third and fourth paragraph of the last PR.

SUNNYVALE, Calif., Jan. 9, 2013

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To clarify remarks in the original release, MJFF does not agree with Amarantus' statements that, to-date, reported behavioural pre-clinical data were positive, and that histology data confirm re-innervation of the striatum due to MANF delivery. MJFF reserves any view on the histology results until the final data are available. In addition, MJFF is not considering additional funding to Amarantus at this time. Amarantus has announced the final data will be available in December.

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SUNNYVALE, Calif., Nov. 27, 2012 /PRNewswire

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"The data obtained in this study provide strong evidence that volume distribution from the site of delivery in the brain is unlikely to be an impediment to MANF's clinical progress," said John W. Commissiong, PhD, Chief Scientist at Amarantus. "Volume distribution from the site of delivery appears to have been one of the key shortfalls of previous clinical trials of neurotrophic factors in Parkinson's disease. These results provide a higher degree of certainty that MANF is unlikely to fail in the clinic due to inadequate diffusion volumes."

In studies conducted by Dr. Steven Gill's laboratory at the University of Bristol, MANF and GDNF were injected directly into the striatum of separate groups of rats in order to mimic as closely as possible the treatment setting in humans. Seven days following delivery under best available conditions, MANF's diffusion volume was ~30% greater than GDNF's.

"The results of this study provide further support to MANF's real-world potential as a disease-modifying treatment for Parkinson's disease, and potentially other brain disorders," said Gerald E. Commissiong, President and CEO of Amarantus. "Diffusion from the site of delivery in the brain has been a key problem plaguing the development of other neurotrophic factors for Parkinson's disease for some time. We now have further evidence that MANF appears to have added biological advantages over other neurotrophic factors in development, and the Company intends to leverage these results as we continue to advance our Parkinson's program, as well as explore additional applications for MANF in orphan disease applications. The Company is currently evaluating various delivery technologies to clinically deliver MANF to the brain in Parkinson's disease, and will update the market of its intentions as definitive agreements emerge."

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SUNNYVALE, Calif., Jan. 9, 2013 /PRNewswire

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The data produced comparing optimal doses to the SNc of MANF = 10 ug and GDNF = 10 ug in this model indicate the following at four weeks post-treatment:
1.MANF reduced behavioral deficits by 53%, whereas behavioral deficits with GDNF increased by 20%;
2.MANF produced a 14.4% reinnervation of the striatum, whereas striatum innervation with GDNF was reduced by 9.9%;
3.MANF increased dopamine concentrations in the striatum, whereas striatum dopamine concentrations with GDNF did not increase.

"We are excited about our results with MANF as we have demonstrated superiority to GDNF in a number of key areas related to recovery of function in Parkinson's disease," added Dr. Joseph Rubinfeld, Amarantus advisor and Amgen Co-Founder. "We intend to continue to move our Parkinson's program forward, while also evaluating other disease indications for MANF with potentially accelerated regulatory pathways, including certain orphan diseases. This strategy may significantly reduce MANF's overall time to market versus a Parkinson's-only strategy."

In the study, rodents were lesioned with 6-OHDA on one side of their brain (t = 0). Behavior was tested for baseline (t =1 week) and vehicle, MANF (3 ug, 10 ug or 36 ug) and GDNF (10ug) were injected in different groups of animals at t = 2 weeks. Behavior was tested for drug effect at t = 4 weeks (2 weeks post-treatment) and at t = 6 weeks (4 weeks post-treatment).

The behavioral data achieved statistical significance with a p value of less than 0.03 with animal groups of N=12. The striatum reinnervation data and dopamine concentration data did not achieve statistical significance because the animals sacrificed from the behavioral study were divided into 2 separate groups of N=6 for the analysis of densitometry (striatum reinnervation) and neurochemistry (dopamine concentration in the striatum). The method of analysis of the rat brains did not allow for the densitometry and neurochemistry to be analyzed simultaneously in the same animals, leading to groups of N = 6 or less, which was insufficient to achieve statistical significant.

[/u]The Company believes the data are positive, even without statistical significance due to small groups of animals in the densitometry and chemistry data, because there are consistent internal results correlating behavior, stereology, densitometry and neurochemistry, most notably at MANF = 10 ug and GDNF = 10 ug. The Company is preparing to initiate IND enabling studies for MANF as a disease-modifying drug candidate for Parkinson's disease.

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(Apr. 8, 2013)
Amarantus Announces Preclinical Development Timeline for MANF Therapeutic
SUNNYVALE, Calif.-- Amarantus BioScience Holdings, Inc. (OTCQB: AMBS), a biotechnology company discovering and developing treatments and diagnostics for diseases associated with neurodegeneration and apoptosis, today provided a timeline of key activities and milestones related to the preclinical development of MANF (Mesencephalic-Astrocyte-derived Neurotrophic Factor). The Company is currently focused on developing MANF across three broad categories: Parkinson's disease and Traumatic Brain Injury; large systemic applications such as Ischemic Heart Disease and Diabetes; and orphan indications.

“We plan to move forward on a number of fronts this year with MANF, leading potentially to one or more Investigational New Drug (IND) filings in 2014,” said Gerald E. Commissiong, President and Chief Executive Officer of Amarantus. “The pace and scope of activities outlined today reflect the unique properties of MANF, the positive results reported earlier this year in neuroprotective and neurorestorative animal models of Parkinson’s disease and supportive data from the published literature.”

The upcoming activities related to Amarantus’ Parkinson’s disease program include:
• Create mammalian GMP production processes for MANF; the Company has sourced the expertise for these activities, and has started development of the supporting analytical and bioanalytical assays;
• Form a partnership agreement in the third quarter of 2013 with a firm specializing in Convection-enhanced delivery (CED) of drugs to the brain;
• Initiate non-human primate pharmacology studies in Parkinson's disease models in the second half of 2013 in order to establish an appropriate dosing regimen for human clinical studies;
• Potentially evaluate MANF gene therapy based upon upcoming developments in the field of neurotrophic factors for Parkinson’s disease, and the Company’s current patent position whereby the Company owns exclusive rights to MANF gene therapy applications in all vector systems.

Additional planned activities are expected to include:
• Conduct pharmacokinetic and pharmacodynamic (PK/PD) studies, with data available in the third quarter of 2013, to evaluate the biological properties of MANF when administered systemically, with data to be released as it becomes available;
• Conduct pharmacology studies in traumatic brain injury, ischemic heart disease, diabetes and certain other animal models in the third quarter of 2013, with data to be released as it becomes available;
• Evaluate MANF in a variety of animal models of orphan diseases in the third quarter of 2013 that represent significant market opportunities, and where there is limited or very limited competition;
• Initiate MANF toxicology studies upon development of a master cell bank of MANF protein material as one of the final pre-IND steps;
• File an IND in 2014.

“Based on our progress with these preclinical activities and the interest and level of data in specific indications, we will seek to partner with biopharmaceutical companies or appropriate not-for-profit disease foundations in order to accelerate our development program and assist in recruiting patients for future clinical studies,” said Mr. Commissiong. “We will prioritize our clinical development programs based upon the outcome of the pharmacology studies that will begin in the third quarter of 2013 for the indications outlined here today. We intend to give highest priority to those indications where we have a shorter path to market, and where non-dilutive financing is available to support further development. Fortunately for the Company, it is likely that many of the pre-clinical studies will have applications across indications, meaning we will get the advantage of a particular set of data enabling multiple indications.”

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GLTA,
GO AMBS