Ebola prevention hits home

Ebola preventionHow are all the thousands of hospitals around the world and here in the US gearing up to deal with the potential arrival of a patient with Ebola?

The importance of this issue and how it is resonating so strongly in the medical field hit home for me a bit more a few days ago as I was walking in front of a local medical clinic and saw the sign at left.

In a way it is an unsettling sign because it illustrates the threat, but at the same time it is good to know that careful measures are being implemented.

The Betatrophin Blues

All the recent high-profile papers that are having troubles are bumming me out.

The latest example is the “Betatrophin” Diabetes paper from Harvard last year.

Yesterday it was called into major doubt by a new Cell paper from a group led by Jesper Gromada at Regeneron.

The authors of the original 2013 Betatrophin paper–Doug Melton’s team at Harvard– indicated in their own accompanying, somber perspectives piece also in yesterday’s issue of Cell that they agree that their 2013 report was largely incorrect. This unfortunate turn of events is based on both the new Regeneron paper and the Melton lab’s own follow up work.

Rewind back to 2013 when the Betatrophin finding first came out and it was hard not to get into the story at that point given how it was being portrayed. A Harvard press release made little doubt that this was a seminal discovery for Diabetes research:

The hormone, called betatrophin, causes mice to produce insulin-secreting pancreatic beta cells up to thirty times the normal rate…it could eventually mean that instead of taking insulin injections three times a day, you might take an injection of this hormone once a week or once a month, or in the best case maybe even once a year.

The 2013 paper itself was also very bold with statements such as:

Thus, betatrophin treatment could augment or replace insulin injections by increasing the number of endogenous insulin-producing cells in diabetics.

Betatrophin

They raised expectations sky high.

I blogged about that apparent blockbuster finding here back then in 2013 and I definitely was excited about it given how it sounded. Now there’s a major letdown. The new paper’s title alone pretty much says it all:

ANGPTL8/Betatrophin Does Not Control Pancreatic Beta Cell Expansion

You can see the graphical abstract from this paper at left in which the authors report that Betatrophin, which now should probably go by the more objective name ANGPTL8, does not substantially impact beta cell growth, but rather seems to have a notable role in mouse triglyceride metabolism. ANGPTL8 is probably a very interesting molecule, but it is not what it seemed to be.

In the perspectives piece, the Betatrophin authors say that boosting their N of mice has led their main conclusion to come into doubt:

In Yi et al. we reported an average beta cell replication rate of ∼4% in betatrophin-injected mice (n = 7); with five additional experiments (n = 52 mice in total), the average beta cell replication rate in betatrophin-injected mice drops to 1.2%. While still significantly above control levels (p = 0.016 for all experiments) of beta cell replication (0.6%), the conclusion from Yi et al. must be corrected and modified with respect to the magnitude of the effect.

It’s now unclear what the fate of the 2013 Betatrophin paper will be moving forward given that its central argument is incorrect and even the naming of the molecule “Betatrophin” is indeed perhaps not appropriate any more.

It’s hard to say what went so wrong here, but I am feeling kind of blue about the whole thing.

Diverse Stem Cell Person of the Year 2014 Award Finalists

Stem Cell Award Poll 2014With more than 4,142 votes cast, the readers of this blog have chosen the top 12 finalists for the Stem Cell Person of the Year Award for 2014 from the 27 nominees.

You can see the final vote tallies at left. The votes came from more than 50 countries with some interesting geographic patterns (I may do a post on that as a follow up).

I’ve pasted the brief bios of the twelve finalists below at the end of this post.

Now comes the tough task for me to pick a single winner from this amazing group. I will announce the Stem Cell Person of the Year 2014 within 1-2 weeks.

The finalists are a diverse group. They include scientists from academia and industry, patient advocates, a blogger, and the Pope. We have six male and six female finalists who live all around the world including in the US, Japan, Sweden, Canada, and Vatican City.

I’m happy to see both some familiar faces from nominees and finalists from past years and new ones too.

Who would you pick as the one winner and why? Post in the comments.

Finalists Bios (including in bold quotes from nominators)

Chris Fasano. A principal investigator at the Neural Stem Cell Institute where he uses stem cells to study early nervous system development. “Chris stands out for his energy, enthusiasm, dedication to the field, creativity and accomplishments.”

Don C. Reed. Long-time stem cell research advocate who played a key role in the success of Prop 71 and the creation of CIRM. “A tireless stem cell advocate always there to make a positive difference.”

Janet Rossant. Professor, University of Toronto. Stem Cell Researcher and Past President, ISSCR. “She works tirelessly to create new opportunities and collaborations…globally respected for her work in early development and embryonic stem cells”

Judy Roberson. Long-time Huntington’s Disease patient advocate. “She makes concrete positive developments happen such as millions of dollars in research funding for HD.”

JuuichiJigen. Japanese blogger who investigates scientific misconduct and played a key role in revealing the STAP scandal. He was the first to investigate and bring to the public of problems with STAP papers. His investigations demonstrated the role of social media and post-publication peer review in rapid self-correction of science.”

Malin Parmar. Associate Professor, Developmental and Regenerative Neurobiology, Lund University. Top neural regeneration scientist. “Young, hard worker who is doing very well”.

Masayo Takahashi. Stem cell researcher leading the team that is doing the first ever clinical study based on human iPS cells. “Creative and courageous clinical stem cell researcher.”

Pope Francis. Leader of Worldwide Catholic Church. “Strong supporter of adult stem cell biotechs and research”.

Robert Lanza. CSO of Advanced Cell Technology, which has multiple ES cell-based clinical trials ongoing. “Visionary and practical so makes the impossible possible with stem cells”.

Susan Solomon. Co-Founder and CEO of The New York Stem Cell Foundation (NYSCF). Remarkably effective advocate for stem cell research. “Not many leaders have created their own research laboratories and raised $100 million plus. Seriously, what an accomplishment!”

Ted Harada. Leading stem cell research advocate and very effective ALS patient advocate. “An Energizer Bunny for the ALS community and stem cell advocate”

Tory Williams. Stem cell advocate and author of the 2014 book, Inevitable Collision. Co-Founder and Executive Director of the Alabama Institute of Medicine (AIM). “A true hero who inspires and makes real things happen like AIM”.

Yamanaka Interview on Clinical Use of Pluripotent Stem Cells

Dr. Shinya Yamanaka

Dr. Shinya Yamanaka.                                           Photo from CiRA, Kyoto University

I invited Nobel Laureate Shinya Yamanaka to do an interview on the future of clinical translation of induced pluripotent stem cells (iPSC).

He provides some intriguing new insights into the iPSC field and the broader stem cell arena.

PK: The Takahashi Team’s active Clinical Study using iPSCs to make RPEs to treat Macular Degeneration has generated a great deal of excitement. Can you please share your perspectives on the importance of this work and the team involved? 

SY: This is the first study to apply iPSC technology to human care. This is a very important study, because if it succeeds it will show that iPSCs can be safely used in humans and also their potential for cell transplantation treatment. We collaborated with Dr. Masayo Takahashi of RIKEN CDB by evaluating the safety of the iPSCs and iPSC-derived cells that were used for the cell transplantation. She is an excellent researcher, and I am not surprised that her team is the first to have succeeded in this transplant.

PK: Any cutting edge investigational clinical work such as this has some risks. Could you please comment on the potential risks in this iPSC trial? Are there some elements here such as preclinical data, the number of cells used, or the target tissue of the eye that lower risks?

SY: One of the major concerns is whether transplanted cells such as the RPE sheets will cause tumors. In our collaboration with Dr. Masayo Takahashi’s team, we evaluated the safety of iPSCs and iPSC-derived cells by genome and epigenome analysis. While we minimized the risk to a level acceptable for clinical trials, we really cannot confirm how the cells will respond until we actually do experiments with humans, which is why this project is so important. One advantage of treating age-related macular degeneration is that it is easy to detect any abnormalities in the eyes, which is why the disease is a good starting model for iPSC-based treatment.

PK: As the inventor of iPSCs did you imagine 7-8 years ago that a patient in a clinical study in 2014 would already have received an iPSC-based treatment? How was this rapid translation from bench to bedside possible?

SY: I was surprised that after the announcement of human iPSCs in 2007, Dr. Takahashi told me that she would bring iPSC to the bedside within five years. I thought it possible technically speaking, but doubted it could be done so soon, since we needed to improve the technology and get government approval. It took 7 years, which is remarkable considering the work required. Both the accomplishment and the speed at which it was achieved are testaments to Dr. Takahashi’s leadership and her strong team.

The rapid transition is because many bright and passionate people are in the iPSC field. The funding and infrastructure provided by the Japanese government is also a major factor, as these have encouraged excellent scientists to enter the field.

PK: We are also starting to hear more about Dr. Jun Takahashi’s Team’s important work towards using iPSCs to treat Parkinson’s Disease. Can you please tell us more about that?

SY: Prof. Jun Takahashi’s team at CiRA is working on cell therapy for Parkinson’s disease, aiming to transplant iPSC-derived dopaminergic neural progenitor cells into PD patients’ brains. Early results suggest this treatment can be effective, and his team has established the protocol for transplantation. They are now focusing on validating its safety using monkey models. We hope his work will soon reach the operating room within the next few years.

PK: What other clinical applications of iPSC technology are in the works and that might begin clinical studies in the next few years?

SY: There are two major clinical applications of iPSCs, namely regenerative medicine and drug discovery. CiRA has a number of researchers working on either or both. For regenerative medicine, Prof. Koji Eto at CiRA is working on generating platelets via iPSCs, and we expect this will also proceed to clinical research in a few years. Besides work at CiRA, a team at Keio University has a plan to conduct clinical research on patients with acute spinal cord injury in four to five years, while Osaka University and Keio University hope to transplant iPSC-derived cardiac myocytes into patients with heart diseases within a few years. CiRA is collaborating with these teams as well.

Regarding drug discovery, you may have heard recently of CiRA’s Prof. Noriyuki Tsumaki’s paper about statins effects on bone growth, which was published online in Nature last month.

PK: Some in the media are taking about a certain tension between clinical iPSC work in Japan and clinical iPSC work in the US. Do you believe such a tension exists and if so, why? What does it mean for the iPSC field overall?

SY: I am not sure what “tension” means. I understand that both competition and collaboration exist between the US and Japan.

PK: How do you view hESCs today? Are there hESC clinical trials or potential applications that are of particular interest? What is your view of the argument by some that hESC are no longer needed?

SY: Human ESC was a great discovery for regenerative medicine and also instrumental to the discovery of iPSC and the type of medical treatments we are aiming to apply iPSC. At the same time, the ethical issues that hESC possess mean that as iPSC technology improves, hESC will be less needed. Still, iPSC is a new technology, and its safety and efficacy still needs to be confirmed. In addition, there may be some therapies for which hESC are better than iPSC. Thus, I think basic and clinical research of hESC is also important and should be done in parallel with iPSC research.

PK: What excites you most about the stem cell/regenerative medicine field right now today?

SY: I am excited about the possible number of people treated with iPSCs. This field has great potential to provide treatments for currently incurable diseases. Hopefully, within 5 years, we will refer to Dr. Masayo Takahashi’s AMD work as just one of many patient studies using iPSCs.

PK: Where do you see the iPSC field and the broader stem cell field in say 5-10 years?

SY: It is pretty amazing how much it has changed in the past years, so predicting the next 5-10 years is very difficult. I certainly hope we will see more diseases being treated with iPSC and related technologies such as direct reprogramming. I also hope that iPSC will be used more widely and routinely in drug development.

PK: What advice would you give to young scientists today who are excited about a career in stem cells/regenerative medicine?

SY: Through biomedical research, you could help thousands of patients in the future. Stem cells provide unprecedented opportunities in stem cell therapy and drug development. Biology of stem cells itself is extremely interesting. I hope many young scientists will enter to this field.