Who deserves the patent on using CRISPR-Cas9 in human cells? Take our poll

There is no hotter technology than CRISPR-Cas9 gene editing tools.

Perhaps it is not surprising then that there is a patent dispute over it, which falls into two camps:

(1) Jennifer Doudna & Emmanuelle Charpentier, and (2) Feng Zhang.

Who deserves the intellectual property for use of CRISPR-Cas9 in human cells?

Take our poll.

Interview with Bioheart CSO, Kristin Comella: trial update, MD stem cell training & FDA

Kristin ComellaI invited the Chief Scientific Officer (CSO) of Bioheart, Kristin Comella, to do an interview after hearing some buzz that this could be a critical time for the company and that it might have been recently visited by the FDA.

Note that Comella not just Bioheart CSO, but also the primary instructor for physician training in stem cell methods offered by the company US Stem Cell Training.

Can you update us on how Bioheart is doing with its clinical trials/INDs?

Comella: Our completed clinical trials of MyoCell to date have been primarily targeted to patients with severe, chronic damage to the heart who are in Class II or Class III heart failure according to the New York Heart Association, or NYHA, heart failure classification system. We have completed various clinical trials for MyoCell including the SEISMIC Trial, a 40­patient, randomized, multicenter, controlled, Phase II­a study conducted in Europe and the MYOHEART Trial, a 20­patient, multicenter, Phase I dose­escalation trial conducted in the United States. We were approved by the FDA, to proceed with a 330­patient, multicenter Phase II/III trial of MyoCell in North America and Europe, or the “MARVEL Trial”. Thus far, 20 patients, including 6 control patients, have been treated. Initial results for the 20 patients were released at the Heart Failure Society of American meeting, showing a significant (35%) improvement in the 6 minute walk for those patients who were treated, and no improvement for those who received a placebo. On the basis of these results, we have applied for and received approval from the FDA to reduce the number of additional patients in the trial to 134, for a total of 154 patients. The SEISMIC, MYOHEART, and MARVEL Trials have been designed to test the safety and efficacy of MyoCell in treating patients with severe, chronic damage to the heart.

In addition, we  received approval from the FDA to conduct a Phase I safety study on 15 patients of a combined therapy (MyoCell with SDF­1) called the REGEN trial. Advancement of the MyoCell and MyoCell SDF­1 clinical development programs is contingent, among many factors, upon the Company obtaining access to sufficient funding to execute the necessary clinical trials to achieve proof of efficacy and regulatory authorization to market such products.

Bioheart has spent over $125 million researching cellular therapies for patients and supporting clinical trials. We are committed to bringing more treatments forward and all revenue that is brought into the company is put towards advancing this science. Our FDA phase 3 MARVEL Trial for congestive heart failure patients is budgeted to cost $10 million dollars for 100 patients. Trying to complete double blind placebo controlled trials is very expensive and there is limited funding for companies who are trying to complete these trials.

How did you and Bioheart get interested in stem cell training courses for MDs? Is US Stem Cell Training owned by Bioheart? Is there some common ground between the missions of the two?

Comella: We are currently offering courses for physicians through US Stem Cell Training which is a wholly owned subsidiary of Bioheart. The field of regenerative medicine is expanding very rapidly and physicians may not have adequate exposure to these topics during medical school. Our goal is to provide physicians with the latest research in cellular medicine. The course includes didactic lecture and hands on demonstration with topics including:

  • Stem Cell Biology
  • Embryonic Cells
  • Induced Pluripotent Stem Cells
  • Bone Marrow Stem Cells
  • Adipose Stem Cells
  • Platelet Rich Plasma
  • GMP Training
  • Regulatory Environment
  • Fat Harvesting Procedure
  • Bone marrow isolation Procedure

The course is constantly updated with new research and data as more studies are published. The goal is to familiarize physicians with the latest research and how this may affect their practice. We also host a monthly webinar series which includes journal clubs and guest lecturers. This field is growing and we want to provide physicians an opportunity to learn more about regenerative medicine. Many patients are asking their physicians questions about regenerative medicine and our hope is to bridge the gap between basic research and clinical practice.

What are your views on the recent FDA draft guidances including on adipose in which the FDA suggested that SVF is a biological drug?

Comella: The FDA has recently released a draft guidance document regarding the use of human cell and tissue products used during the same surgical procedure from adipose tissue and has requested comments from the public on this guidance. Please note that guidance documents represent the FDA’s “current thinking on the scope” of the topic. “FDA’s guidance documents do not establish legally enforceable responsibilities. Instead, guidances describe the FDA’s current thinking on a topic and should be viewed only as recommendations, unless specific regulatory or statutory requirements are cited. The use of the word should in FDA’s guidances means that something is suggested or recommended, but not required.”

We do not believe that the current draft guidance document will affect our ability to offer in-clinic cell therapy from fat to our patients. We understand that the FDA’s draft document has elicited much resistance from the public and highly respected organizations such as AABB Center for Cellular Therapies and The Academy of Regenerative Medicine have voiced their opposition.

It is impossible to predict what the FDA will do regarding any in clinic therapies so I can only tell you what has happened in the past. In December of 2014, the FDA visited our lab as well as three physicians who are doing SVF procedures. The FDA took no action against anyone and did not stop the SVF procedures. Many of you have seen that these procedures can provide benefit to patients who have failed other therapies. Our primary goal has been and will continue to be safety and well-being for our patients.

Oftentimes, emerging technologies are met with skepticism and criticism. When stents were first introduced as an option for patients having a heart attack, many famous cardiologists criticized them because of the risk of restenosis (blockage). Yet stenting is now a common cardiac procedure. Cellular medicine has existed since the 1960s and is commonly used for cancer patients under the term Bone Marrow Transplant. These treatments were never put through double blind placebo controlled trials; nevertheless, we accept them as the standard of care. In addition, cellular medicine for degenerative diseases has been the subject of thousands of animal studies and clinical trials. Many of these studies date back to the 1980s. I think a fair question to ask a patient who has failed to benefit from traditional medicines and therapies is “how many studies would you like to see before you try to harness your body’s own healing potential”. Most patients are willing to try something experimental and, provided that companies are clear on the possible risks versus rewards, these therapies should not be withheld from the public.

I think that the body’s natural healing mechanisms are fascinating. The ability to harness this natural healing potential to reverse the effects of degenerative diseases or injuries is very powerful. We have a lot to learn about regenerative medicine but we are now starting to realize the potential by bringing these therapies to clinic. With any new therapies, there are challenges to bringing them to market. In addition, it is difficult to navigate the regulatory environment because these therapies are unlike any others currently available to patients. Cellular therapies should not be regulated in the same way as drugs and devices and many regulatory bodies are trying to establish new rules and guidelines. I am not sure that a person’s own cells should be regulated in the same way as a drug that is manufactured. It is important to advance science with patient safety as the primary interest. We have treated patients whose lives have completely changed for the better because of regenerative medicine and this is why I love this field!

Was US Stem Cell Training or Bioheart recently visited by the FDA? If so, how did the visit go and could you please provide a copy of the 483 form?

Comella: In December of 2014, we had an unannounced inspection from the FDA of our lab as well as three physicians who are doing SVF procedures. The FDA requested copies of our protocols and information about all of the materials that are utilized in the SVF process. They also specifically requested information regarding several IRB protocols. The FDA toured our lab facilities as well as the facilities of three different physicians. The FDA took no action against anyone and did not stop the SVF procedures. No warning letters (i.e. 483s) were issued. We received notice that all the documents were sent to CBER who reviewed and at this time they have no additional questions. Therefore the investigation was closed. Please note that this is the second investigation for Bioheart and we have not received any warning letters (483s). Our lab is a registered FDA tissue bank (FEI: 3005825762) and we are subject to unannounced FDA inspections.

Gordie Howe family reportedly invested in stem cell business they touted for treating their father

Gordie HoweIt has been one of the most hyped stem cell stories in history.

Hockey legend Gordie Howe had a devastating stroke last fall and supposedly a stem cell treatment in Mexico from for-profit stem cell businesses, Stemedica and Novastem, caused a remarkable recovery in Howe.

What really happened?

Today a new article on a fresh investigation into this story sheds some important additional light on it including the bombshell that Howe’s family has invested in Stemedica.

For background, the Howe treatment was given via stem cell company Stemedica and its partner in Mexico, Novastem. Reportedly, Anesthesiologist Cesar Amescua did the actual stem cell transplant into Howe.

Back immediately after the treatment in Mexico, Howe’s family raved about it. The effects were described by them and others as miraculous.

Sports commentator Keith Olbermann went ‘weak in the knees’ at how amazing it all seemed in a gushing interview with Stemedica leader, Maynard Howe (no relation to Gordie) on the air.

I was happy to see Gordie doing well, but skeptical for a variety of reasons that stem cells were the reason. If anything, David Gorski was even more skeptical.

Why?

First, the timing of the recovery seemed way too fast for a stem cell treatment. Howe reportedly had gotten better almost immediately after getting the cells, which would normally be expected to take quite some time to work — days or weeks instead of a few hours.

In addition, Howe’s recovery could have been a result of any number of things including simply placebo effect or a natural recovery from the stroke. Many were claiming out right that the stem cells worked magic.Duncan Stewart

Further, Howe received the treatment for free, while it would normally cost $30,000, and the Howe family was not shy about telling the world how great it all seemed to be and how wonderful Stemedica was. It’s understandable I suppose that they were enthusiastic about a company that they believed had helped their dad.

Stemedica and Novastem received the equivalent of an all out PR blitz in the media. Additional business seemed to head their way.

CTV News/W5 has now investigated and reported on what they found both on TV and online.

I encourage you to watch the videos as they are very striking.

Dr. Duncan Stewart, the scientific director of regenerative medicine at the Ottawa Hospital Research Institute and a stem cell researcher (pictured above from video screenshot), agreed to visit Stemedica and Novastem as part of the CTV investigation. By way of disclosure, I was separately invited to visit as well, but declined because I felt concerned about how this story had unfolded.

Stewart viewed the situation as a good news/bad news kind of thing as described on the Ottawa Hospital website:

“The good news is that the stem cells that Mr. Howe received were produced in a facility in the U.S. that complies with appropriate regulations, so we know that these were high-quality stem cells,” said Dr. Stewart. “I was also encouraged to see that the licensing agreement between the stem cell production facility in the U.S. and the clinic in Mexico requires that the stem cells be administered through clinical trials.”

“The bad news is that the clinic in Mexico is not in a position to perform clinical trials that meet Canadian and U.S. regulatory standards,” added Dr. Stewart. “This means that it is not clear whether meaningful results will be collected and whether patient safety will be adequately protected. It is also important to remember that this is not a research facility – it is a for-profit business.”

Howe’s recovery itself seems indisputable and is great news, but what caused it?

Nobody can be sure.

Dr. Steven Cramer, a neurologist at University of California Irvine, examined Howe and suggested possible non-stem cell treatment-related reasons as to why Howe might have bounced back:

“Cramer says physical and occupational therapy could have played a role or there may have been a spontaneous improvement, which happens sometimes during the first three to six months. But Gordie’s recovery may be due to the so-called “piss-and-vinegar gene” — a fighting spirit or drive that Gordie has in abundance, Cramer said.”

Another notable thing mentioned in the coverage of this investigation was this shocker:

“Following Gordie’s amazing recovery they have invested in Stemedica, and Murray Howe is hoping to begin studies of stem-cell treatment for brain injuries at his hospital in Ohio.”

Gordie’s children have invested in Stemedica?  This investment is also mentioned in the CTV online piece, but only near the end and without any details.

This purported investment, if confirmed, means that Gordie Howe’s family have a vested interest in the success of the company that treated their father. This connection raises some serious concerns.

See here for Leigh Turner’s insightful perspective on the Howe family investment in Stemedica including five key questions that he believes the family should address:
  • Who in the Howe family invested in Stemedica?
  • What is the size of this investment?
  • Where was this investment first discussed?
  • When did members of the Howe family make this investment?
  • Why did they decide to invest in Stemedica, why have reporters not described their investment until this weekend, and have any Howe family members done media interviews without first disclosing this investment?
In the end we may never know the answers to these questions or the reason that Gordie bounced back so well, but this story illustrates the complexity of the stem cell for-profit clinic world and the difficulty in separating fact from speculation or promotion.

Doctors call for Dr. Oz to be booted from Columbia

DrOZControversial TV physician Dr. Mehmet Oz hasn’t had a great year what with his disastrous testimony before Congress.

Now Dr. Oz has been slammed by a group doctors from across the country. Update: Orac points out that these doctors have some of their own baggage when it comes to science.

They reportedly want him removed from Columbia because of alleged quackery.

These other doctors who want Oz’s neck don’t mince words according to the NY Daily News:

“He’s a quack and a fake and a charlatan,” said Dr. Henry Miller of Stanford, the first person to sign the poison-pen letter.

No pulling of the punches there by Miller (pic below).

That’s got to hurt for Oz, especially with other events this year including the green coffee bean scandal, a story broken by Ivan Oransky.
henry miller stanford

His Congressional testimony performance was a far cry from his bombastic circus-like persona in his TV show.

Before Congress, he was rather meek and couldn’t really defend himself from charges that on his show he sells hype and could be misleading his audience. This contrast was reminiscent of the scene in The Wizard of Oz when the wizard is revealed for what he really is behind the curtain.

I haven’t been an Oz fan myself to put it mildly, in part because he did a terrible performance on stem cells with Michael J. Fox on Oprah.

Miller of Stanford Med School explained his thinking on why Columbia has chosen to keep Oz:

“I think I know the motivation at Columbia,” he continued. “They’re star-struck, and like having on their faculty the best-known doctor in the country. But the fact is that his advice endangers patients, and this doesn’t seem to faze them. Whether they’re hoping Oprah will come and endow a center for homeopathic medicine, I don’t know.”

It seems like Oz has sort of had his cake and eaten it too over the years. Being a real doctor at Columbia and then playing this wizard-like showman on his TV show. Will that dual life end? Maybe not any time soon.

Columbia continues to defend him:

“Columbia is committed to the principle of academic freedom and to upholding faculty members’ freedom of expression for statements they make in public discussions,” said Columbia University Medical Center spokesman Doug Levy.”

Here is the full text of the letter as posted on the Washington Post website:

Lee Goldman, M.D.
Dean of the Faculties of Health Sciences and Medicine
Columbia University

Dear Dr. Goldman:

I am writing to you on behalf of myself and the undersigned colleagues below, all of whom are distinguished physicians.

We are surprised and dismayed that Columbia University’s College of Physicians and Surgeons would permit Dr. Mehmet Oz to occupy a faculty appointment, let alone a senior administrative position in the Department of Surgery.

As described here and here, as well as in other publications, Dr. Oz has repeatedly shown disdain for science and for evidence-based medicine, as well as baseless and relentless opposition to the genetic engineering of food crops. Worst of all, he has manifested an egregious lack of integrity by promoting quack treatments and cures in the interest of personal financial gain.

Thus, Dr. Oz is guilty of either outrageous conflicts of interest or flawed judgments [sic] about what constitutes appropriate medical treatments, or both. Whatever the nature of his pathology, members of the public are being misled and endangered, which makes Dr. Oz’s presence on the faculty of a prestigious medical institution unacceptable.

Sincerely yours,

Henry I. Miller, M.D.
Robert Wesson Fellow in Scientific Philosophy
& Public Policy
Hoover Institution
Stanford University
Stanford, CA

Scott W. Atlas, M.D.
David and Joan Traitel Senior Fellow
Hoover Institution
Stanford University
Stanford, CA

Jack Fisher, M.D.
Professor of Surgery (emeritus)
University of California, San Diego
La Jolla, CA

Shelley Fleet, M.D.
Anesthesiologist
Longwood, FL

Gordon N. Gill, M.D.
Dean (emeritus) of Translational Medicine
University of California, San Diego
La Jolla, CA

Michael H. Mellon, M.D.
Pediatric Allergist
San Diego, CA

GIlbert Ross, M.D.
President (Acting) and Executive Director
American Council on Science and Health
New York, NY

Samuel Schneider, M.D.
Psychiatrist
Princeton, NJ

Glenn Swogger Jr. M.D.
Director of the Will Menninger Center for Applied Behavioral Sciences (retired)
The Menninger Foundation
Topeka, KS

Joel E. Tepper, M.D.
Hector MacLean Distinguished Professor of Cancer Research
Dept of Radiation Oncology
University of North Carolina School of Medicine
Chapel Hill, NC

Medical Board Yanks License of California Stem Cell Clinic Doc

william raderThe California State Medical Board has revoked the license of Dr. William C. Rader, a psychiatrist and stem cell clinic doctor.

The revocation was stayed and there was a 180-day actual suspension, but Rader was placed on probation for a period of 7 years.

Rader has been heavily involved in stem cell tourism and more specifically in facilitating patients receiving fetal stem cell “treatments” outside the US in a variety of countries including the Bahamas, the Dominican Republic, and Mexico.

He also wrote a book “Blocked in the USA The Stem Cell Miracle” promoting these stem cell interventions and did promotion via his Internet presence. Over the years his companies included The Dulcinea Institute, Medra, Inc., and Stem Cell of America, Inc.

A simple Google search reveals that Rader’s involvement with stem cells has been intensely controversial. He was, for example, one of the subjects of a BBC expose (see video below, note that it is just part 1 of 4…curiously I couldn’t find part 4 on YouTube).

If Rader has been so controversial for a very long time, why has it taken the California State Medical Board so long to take action? It’s not clear.

Rader is or was somewhat of a celebrity figure. He was married to actress Sally Struthers for a time. In this recent matter regarding his license and the California Medical Board, celebrity lawyer Robert Shapiro of OJ fame was part of his legal team.

The California Medical Board made seven allegations against Rader:

“Complainant has alleged seven causes for discipline against Respondent for gross negligence (Bus. & Prof. Code’ § 2234, subd. (b)), repeated negligent acts(§ 2234, subd. (c)), false and/or misleading advertising (§ 2271 ), disseminating false or misleading statements (§ 651, subd. (a), (b)(l), (b)(2), (b)(3), and (b)(7)), dishonesty or corruption(§ 2234, subd. (e)), general unprofessional conduct(§ 2234), and violation of a provision or provisions of the Medical Practice Act(§ 2234, subd. (a)). The allegations were made in connection with Respondent’s advertising for, recommending, and or participating in the use of fetal stem cell therapy on human beings.”

The court documents would seem to indicate that to some extent Rader acknowledged certain elements of the allegations. Interestingly, a number of specific patient cases are discussed and are very concerning related to, for example, apparent lack of proper informed consent.

Patients would pay a fee of $30,000 per treatment as well as travel costs. It is not entirely clear how many patients actually were administered stem cells via Rader’s efforts, although he has claimed to have treated as many as 1,500-2,000 people. However, the court document shed some doubt on that:

“In the book, Respondent wrote that he had treated over 1,500 patients with fetal stem cell therapy. At the hearing, Respondent claimed that statement was not true, and that he wrote it to give potential patients a better understanding of what he was doing. He testified that the effect would have been “attenuated” (Respondent’s term) if he wrote that he only referred patients to health care professionals practicing in foreign countries. Respondent also wrote that 96 percent of the 1,500 patients he treated had a positive outcome. At the hearing, he admitted that the figure was only a general statement and not the result of a statistical analysis.”

Even if he only “treated” a fraction of that number, say 500 people, then that number of clients would still have potentially generated $15 million USD in income. Given the large sums of money involved here it is notable that there was no apparent fine involved in this medical board action. I’m not sure if medical boards can issue monetary fines. Do you guys know?

Oddly, at the hearing Rader apparently denied treating any patients with stem cells at all directly, but asserted that patients only got the interventions through other doctors:

“At the administrative hearing, Respondent continued to deny having ever treated anyone with fetal stem cell therapy, and he denied that he was the physician for any patient receiving the therapy. He claimed he only referred potential recipients to foreign physicians. In so doing, he admitted the falsity of a great many statements in the book. For example, (1) he could not describe how many disease processes he had treated; (2) numerous references to patients he had successfully treated; (3) he was the only American doctor who had administered fetal stem cells; (4) references to “my” fetal stem cell patients; (5) references to “my therapy”; (6) numerous references to “my patients”; and (7) by the time a certain study had  been published, he had been administering fetal stem cells to human patients for over five years.”

The new court ruling from Administrative Court Judge H. Stuart Waxman orders quite a few actions and conditions for Rader: the 180-day suspension, correction of falsities, an education course, an ethics course, a clinical training program, practice monitoring, notification of hospitals, etc. where Rader has privileges, may not supervise physician assistants during the probation, is required to obey all laws, provide quarterly declarations, comply with the general probation requirements, must be available for interviews with the Board, comply with certain requirements related to periods of not practicing, and if he violates any of these probation conditions, the probation may be suspended leading again to active, potentially long-term license revocation.

This action to me seems like a positive for patients and the stem cell arena more generally, but again why did it take so long? Rader’s actions presented significant potential risks to patients on both health and financial levels and posed issues for the stem cell field, where many solid, evidence-based stem cell treatments are in development.

Unproven stem cell clinics are widespread throughout the US and in California. Our state is one of a few particular hot bed states for this stuff. Could this action signal more to come in the way of steps from the California State Medical Board in the dubious stem cell clinic arena?