Replies to post #129965 on Amarantus Bioscience Holdings Inc (AMBS)

[Rotten Johnny]

no know cure - however, does MANF prevent it

just askin...

MANF has been prostituted by the Commissiongs since 2002 - or 20 years ago - and it hasn't done squat:

https://www.sec.gov/Archives/edgar/data/1424812/000114420414035418/R26.htm

In 2007, Neurotrophics established an agreement with EMS Development Group to acquire the intellectual property rights to a protein compound, mesencephalic astrocyte-derived neurotrophic factor (“MANF”), from Prescient Neuropharma Co. MANF was discovered by Dr. Commissiong while working for Prescient in 2002, as a drug candidate with promising therapeutic properties for treatment of syndromes such Parkinson’s Disease.

MANF along with NeuroPro, LymPro, PhenoGuard, Eltoprazine, ESS, etc., etc., etc. were and are all shit...


The Golden Goose: Preparing PhenoGuard to Lay the Next Golden Egg
November 12th, 2013

Neurotrophic factors don’t come around every day. Since the first neurotrophic factor (NGF) was discovered in 1950’s by Rita Levi-Montalcini’s group, the feat of discovery has been repeated well under 30 times. Moreover, never has the discovery process been meticulously engineered to yield a molecule with an activity profile to treat a specific indication; except in the case of MANF which was discovered for the treatment of Parkinson’s disease. The fact that MANF has been shown to be effective in treating various models of disease in animals gives us a glimpse of what might be possible if we discover more growth factors with the purpose of treating other neurodegenerative diseases.
When I was leading the Neurotrophic Factors Group at the National Institutes of Health in the 1990s, I had a very keen interest in astrocytes because they dramatically outnumber neurons in terms of number of cells and morphological complexity.

After years of research, our team was the first to demonstrate that astrocytes from one region of the brain (substantia nigra) secreted molecules that protected neurons from that region of the brain (dopaminergic neurons of the substantia nigra) better than astrocytes from any other brain region could. Shortly after we published our findings, another group published an almost identical set of results, giving us the confidence that we were on the right track.

From there, another important issue needed to be resolved: In order to use astrocytes as a tool for discovering the neurotrophic factors responsible for the protection we were seeing, we needed a stable source of astrocytes capable of being used in a systematic screening process over and over again. It was here that I reached into some of my early research experience to engineer some proprietary methods to immortalize the astrocytes we were using to generate the initial results in order to turn them into stable cell lines that could be used for neurotrophic factor discovery. We achieved success at 2am one Thursday morning in 1997, the first PhenoGuard cell line (VMCL1) was created, and from there on in my mind it became only a matter of time until multiple neurotrophic factors would be discovered from this methodology. We began using our cell culture to assist companies in drug discovery efforts in 1998, helping Teva Pharmaceuticals in their screening process and ultimately advising them to select Rasagiline from a group of candidates they were evaluating. Rasagiline was approved in 2006, and was the first proof of principle that our cell culture had validity in identifying approvable drug candidates.

Fast forward to 2002, my team discovered and patented MANF using the same cell culture alongside our PhenoGuard cell lines as the biological approach to our neurotrophic discovery program, with MANF ultimately having the signature of protecting dopaminergic neurons that we saw in the cell lines. Shortly after MANF’s sequence was first made public at Dr. Levi-Montalcini’s neurotrophic factors conference in Modena, Italy, the homologue of MANF, CDNF (previously known as MANF2) was discovered by a group at the University of Helsinki using a bioinformatics approach based on MANF. Taken together, MANF and CDNF represent a new neurotrophic factor family discovered as a result of our PhenoGuard discovery platform.

With proof of principle established in various animal models for MANF, the addition of a seasoned drug development organization to the Amarantus team, and the recent move of the Company to a facility where we will have access to all the necessary equipment to restart the PhenoGuard program, I am eager to set about the business of discovering a new neurotrophic factor family. The scientific methods have advanced tremendously in the last decade, which gives me confidence that we will be able to achieve results while deploying significantly fewer resources than we did while discovering MANF. Coupled with our partnering business model, we believe we will be able to find the appropriate partner for PhenoGuard to fully exploit the true value of this technology.
Proving that the discovery of MANF was not serendipitous would represent a massive scientific achievement for the Company in this era of outsourced drug discovery in the pharmaceutical industry. We expect to be in a position to start collaborating on this project in early 2014 having expanded our PhenoGuard cell line library to 88 cell lines from four distinct brain regions associated with Parkinson’s, Alzheimer’s, Clinical Depression and Huntington’s disease.

Science can sometimes be an uncertain endeavor, however with proper parameters established, it has the potential to yield groundbreaking advances in medicine. We believe PhenoGuard could be one such engine in the emerging era of neurotrophic factor development.

Warmest Regards,
John W. Commissiong, PhD

[Rotten Johnny]

MANF Continues to Deliver Heading into 2H-14
June 30th, 2014

Looking back on the last two years, it is amazing to see how the MANF story has unfolded in conjunction with the other corporate initiatives the Company has undertaken including the addition of LymPro and Eltoprazine to our pipeline. The effort to diversify our pipeline was largely initiated to allow the Company’s scientific team to uncover MANF’s true value by identifying market opportunities with the highest net present value, which in biotechnology generally means fastest path to market in an orphan indication. That strategy bore fruit in the middle of 2013, when the Company identified in scientific literature a reference to MANF’s utility in Retinitis Pigmentosa (RP) from the University of Miami’s Bascom Palmer Eye Institute and later secured the intellectual property surrounding that finding. With an exclusive option agreement in hand, the Company has the necessary footing to make further investments in prosecuting MANF’s full potential in RP. Now midway through 2014, the Company is in the process of executing a methodical plan to deliver on the potential for MANF in RP, as well as continuing to expand with data the underlying scientific principles supporting MANF into new areas of research creating valuable intellectual property and know-how. Some of the key steps completed thus far include:

1. The Company has received interim data and is awaiting final results for functional assessments for MANF from a leading contract research lab with specialty in RP rodent models;
2. The Company has received interim data and is awaiting final results for toxicology safety assessments for MANF from a leading contract lab with specialty in rabbit ophthalmological models;
3. Researchers at the University of Miami have completed running additional experiments for MANF in functional models of RP, and expect their findings to be published in peer-reviewed journals in the near future;
4. The Company has received the final report from a leading contract research lab evaluating MANF’s activity in a tau hyperphosphorylation model of Alzheimer’s disease (AD). This study was conducted to confirm work previously published in a Chinese journal;
5. The Company has identified a number of significant independent peer-reviewed research papers published in Chinese journals confirming previously published Western data, as well as identifying new uses for MANF
6. The Company has sourced contract manufacturing organizations capable of commercially manufacturing MANF, completed our due diligence and we expect to select a manufacturer in the third quarter.

All of the interim results we have seen to date in ophthalmology have been positive, which gives us a great deal of confidence heading into the second half of the year that RP will be the first of several INDs for MANF. All of the data being produced will be supportive of additional ophthalmological indications, including Wolfram’s-induced blindness which we are pursuing with Dr. Urano from the Washington University School of Medicine. Beyond these updates, the Company is establishing additional research collaborations with leading institutions in new and potentially groundbreaking areas, as well generating new IP surrounding the use of MANF in these various indications in the third quarter. We will be delivering the confirmatory AD results to the market very shortly, which in turn raises interesting prospects vis-a-vis our LymPro blood test for Alzheimer’s disease. When we first in-licensed LymPro, we had no idea that MANF could have an impact on aspects of the underlying pathophysiology of AD.

However, with recently published data linking tau mis-folding to cell cycle dysregulation and amyloid aggregation, the prospect of MANF becoming the basis for new treatments in AD has become extremely interesting. Reproducibility is the hallmark of good science, and to date MANF has reproducibly demonstrated activity consistent with a breakthrough treatment across a highly valuable spectrum of indications. In addition, we are nearing the completion of the sourcing process necessary to retain our regulatory consulting group with expertise with a specialty in the area of ophthalmology to assist us in the filing of orphan drug designation with the FDA and EMA for MANF in RP. Based on the timelines and estimates we have received, we expect to submit to the FDA and receive a reply regarding our submission in the second half of this year, within the same time frame that we will be looking to up-list our common stock to a national exchange.

Last week we attended a successful BIO convention where we ended up participating in over 60 partnering meetings, and were extremely pleased with the reception we received from the community at large. It is clear that we have become highly visible to larger pharmaceutical companies, as well as promising early-stage companies seeking to partner their assets. The general theme was that each of our assets has tremendous promise within their own right, and most importantly that there is a strong scientific and business case to be made for each becoming a blockbuster asset. Taken together, the synergies created from a business perspective are able to insulate the Company from significant enterprise risk, and our ability to demonstrate progress with any of these assets will lend credibility to the rest of the portfolio. In light of these comments, we are now especially looking forward to the month of July which includes AAIC and our #C4CT Summit, as well as the rest of 2014. We believe the Company is growing stronger by the day and we are excited to share our enthusiasm with our fellow shareholders.

I thank you for taking the time to read this blog and look forward to updating you on additional progress for the Company as we achieve our true potential.

Warmest Regards,
Gerald E. Commissiong
President & CEO

MANF MY arse...



AJMHO