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View Full Version : Installment 29 - Ask the Doctor with Bioheart



Jeannine
04-28-2010, 12:13 PM
We?d like to thank BioHeart for hosting this month?s Ask the Doctor column.


1) I was wondering how being IgG subclass deficiency affects stem cells in the bone marrow or blood or elsewhere? Do I have a lesser amount of stem cells to harvest than normal immune system people? Since we can't expand the supply in the U.S., will it affect the number of stem cells that I will get if I have treatment in the U.S.?

Being IgG subclass deficient does not affect either the quality or quantity of stem cells your body produces. There has been some work evaluating the use of Hematopoietic stem cell transplantation (HSCT) to treat IgG deficiency. HSCT is the transplantation of blood stem cells derived from the bone marrow (in this case known as bone marrow transplantation) or blood.
With the availability of the stem cell growth factors GM-CSF and G-CSF, most hematopoietic stem cell transplantation procedures are now performed using stem cells collected from the peripheral blood, rather than from the bone marrow. Collecting peripheral blood stem cells provides a bigger graft, does not require that the donor be subjected to general anesthesia to collect the graft, results in a shorter time to engraftment, and may provide for a lower long-term relapse rate.
Hematopoietic stem cell transplantation remains a risky procedure with many possible complications; it has traditionally been reserved for patients with life-threatening diseases. Bioheart is not engaged in research in this area.

2) I am curious about the stem cells gotten from liposuction versus the ones from bone marrow. I haven't been able to find a lot comparing the two. From what I have found so far, the liposuction (adipose) stem cells are better for organ, tissue and nerve repair. I saw one site that said you get less stem cells from liposuction than bone marrow. I have MS so I am trying to get the pros and cons of each.

Both bone marrow and adipose tissue contain Mesenchymal stem cells. Each indication should be considered separately when determining the most appropriate stem cell type to utilize for treatment. One advantage to adipose tissue collection is that it is a relatively simple process and tolerated by most patients. Fat tissue can usually be found in abundance within the patient's own body and has a greater number of stem cells than bone marrow. In contrast, the procedure for obtaining stem cells from bone marrow can be painful and often yields a low volume of stem cells. The following articles, which can be found on Pubmed, offer an excellent comparison of bone marrow cells to adipose cells.


Adipose-derived stem cell: a better stem cell than BMSC; Yanxia Zhu, Tianqing Liu, Kedong Song, Xiubo Fan, Xuehu Ma, Zhanfeng Cui

Adipose Tissue-Derived Stromal Cells as a Novel Option for Regenerative Cell Therapy; Nakagami, Morishita, etc. al.

Differences between adipose-derived cells and mesenchymal stem cells in differentiation into cardiomyocytes; Zhang, Gai, Liu.

Direct Comparison of Human Mesenchymal Stem Cells Derived from Adipose Tissues and Bone Marrow in Mediating Neovascularization in Response to Vascular Ischemia; Kim, Kim, Cho, et. al.


Another alternative is myoblasts, which are muscle derived stem cells. These have been shown to be best in addressing damage to heart muscle, since they, unlike stem cells, do not, when adhering to scar tissue, become more scar tissue, as stem cells do.

3) If I have cardiac problems as well as lung problems, would these be treated separately or at the same time? Would different types of stem cells be used for each problem?

We assume that you have congestive heart failure as well as COPD. Both can be treated with either stem cells or with myoblasts. However, it would be risky to treat both at the same time. We are planning to begin treating congestive heart failure with our MyoCell SDF-1 product as soon as the same level of safety and efficacy as we have seen in animals is proven in humans. Our MyoCell product uses myoblasts that have been grown from the patient?s own muscle cells. SDF-1draws the body?s own stem cells to the heart. In our human clinical trials with MyoCell, we have seen good results in treated patients (see below). With MyoCell SDF-1, myoblasts and the body?s own stem cells would work together to repair damage to the heart muscle, resulting in faster and more extensive repair. The MyoCell SDF-1 product would be inserted with a catheter into a number of places in your heart.

For the COPD, treatment would be with an injection of stem cells derived from your own fat tissue. This treatment is already available at Regenerative Medicine Institute.

We would not administer both treatments at the same time. We would wish for the COPD to be resolved before treating the congestive heart failure.

If it is not the case that you have congestive heart failure as a result of attack induced heart damage and COPD as a result of that damage, then the answer above may not apply.

4} I keep hearing about young people with cerebral palsy getting help, but what about those of us who are a bit older? I am 25. Would adipose stem cells be used to treat CP?

We would think that cerebral palsy would be able to be treated with adipose stem cells, but this is not an area of research into which Bioheart is directed.

5) I looked at your site and read about the TGI1200 Cell Isolation System. Do you see this system and the clinical trials you are doing expanding beyond the conditions you are now using it for in your offshore clinical trials?

We are currently researching additional treatment options with the TGI 1200 isolation system but at this time are focused on cardiac and vascular related diseases (acute myocardial infarction, chronic heart ischemia, and lower limb ischemia). Prior to entering any of our clinical trials, we complete years of preclinical research to establish a safe and effective model.

6) I read where the patients that had treatment at Regenerative Medicine will be checked every few months. Does this mean that a patient has to return to the clinic each month or will their own doctor be able to do the testing? Will there be more patients involved in this testing with RMI?

Some of the follow up tests will be completed at the Hospital Angeles where the treatment is administered and others by the patient?s own physician. We have a very detailed protocol which includes regular follow up and monitoring of the patients. We have been working with several academic centers in the US, including Duke University and Columbia University, to develop safe and effective clinical protocols used by our Centers of Excellence for all indications. These are reviewed regularly to ensure that the procedures are optimal.

7) Can you tell me if you plan to treat sensory neural hearing loss - nerve deafness? If not, do you know any clinics that do?

We do not have any plans to treat sensory neural hearing loss. Our focus is in the field of cardiac and vascular related diseases.

8) Do you feel your treatments will reverse cardiac disease enough that only one treatment will be needed or is this strictly on a patient to patient basis as far as additional treatments?

The patients that have participated in our clinical trials have responded in different ways. We have most recently reported the results from part 1 of the MARVEL trial, a Phase II/III, double blind, placebo controlled trial for congestive heart failure patients. Over a 6-month observation period, the most pronounced changes were seen in those treated with MyoCell versus those who received a placebo. Those who were treated with either 400 million or 800 million cells experienced an average increase in the distance covered during their 6 minute walk (6MWD, an established parameter of efficacy utilized in heart failure studies), one of the primary end points in the trial, of more than 91 meters or 35%, whereas in the placebo-treated group an average decrease of nearly 4 meters was seen.

We have completed some preclinical studies to determine the effects of repeat injections of myoblasts and have reported this in Eur Heart J. 2010 Apr;31(8):1013-21. Epub 2009 Aug 22. This study concluded that repeated injection of myoblasts in a model of chronic MI is feasible and safe and induces a significant improvement in cardiac function. We have not started this process in the clinic at this time.

Each patient responds differently to myoblast treatment and some may only require one treatment and some may require subsequent treatments. This would, of course, depend upon the extent of the damage to each patient?s heart and the patient?s own response capability.

9) What is the ball park figure in dollars and time that it takes to get a treatment and/or device approved by the FDA?

It is extremely difficult to put a general timeline or price tag on the path to commercialization. Pharmaceuticals, biologics and devices are regulated differently within the US FDA. In addition, each product within those departments can have a unique regulatory pathway depending on the product indication or the severity of the disease.

For our MyoCell product, after spending many years doing preclinical studies, we began clinical trials in 2002 in Europe and 2004 in the US. We began a Phase II/III trial in the US in 2007. We do not anticipate approval for our MyoCell or MyoCell SDF-1 products before 2013.

We can say that the pathway to approval by the US FDA requires tens of millions of dollars as well as a considerable amount of time. The FDA is naturally concerned with both safety and efficacy. However, the costs for conducting both preclinical and clinical trials have increased dramatically as have the costs for operating a company. With no revenues coming in from its products during clinical trials, and investment not easily found, companies are often unable to complete their very expensive clinicals.

10) Are you a member of ICMS? If not, do you plan to join? How would your company play a role in the organization?

Both the TGI product and the MyoCell product have been reviewed and certified through the cell line advisory board of ICMS. We are currently in discussions with ICMS regarding our future relationship.

Summary:
Bioheart is solely focused on the treatment of cardiovascular related diseases. While most stem cell companies use one particular cell type to treat a variety of diseases, Bioheart utilizes various cell types to treat cardiovascular diseases. Bioheart believes that there are unique qualities within the various cell types that make them more advantageous to treat a particular disease. For instance, muscle stem cells (myoblasts) inherently are able to survive in a low oxygen environment better than any other cell type. They are thus best suited to survive and engraft in the low oxygen environment of chronically damaged, scarred heart tissue. Furthermore, myoblasts are committed to becoming muscle in any environment while other stem cells tend to become the cells in which they come into contact. When myoblasts are injected into scar tissue in the heart they develop into muscle while other stem cells will develop into more scar tissue. Bioheart?s MyoCell? therapy is composed of myoblasts which are injected into the scar tissue that has formed in the hearts of patients suffering from heart failure. The increased muscle formed by MyoCell? in these patients? hearts has been shown to lead to improved cardiac function and an improved quality of life. Myoblasts are not only able to survive and form muscle within the scar tissue of the damaged heart, they can be modified genetically, to attract one?s own stem cells to assist with the regenerative process. Bioheart?s MyoCell? SDF-1 is a gene-modified myoblast composition. The product increases the production of SDF-1, a protein that is capable of enhancing the tissue repair process by attracting the body?s own stem cells. There are many other advantages to using myoblast cells for the indication of heart failure. One of these advantages is their ability to be easily expanded from one small muscle biopsy to billions of cells in the laboratory to replace the billions of cells that have been destroyed during a cardiac event.

Additionally, Bioheart utilizes adipose (fat) tissue-derived stem cells (ADSCs) isolated by the TGI Cell Isolation System for the treatment of acute myocardial infarction or heart attacks. After a heart attack, the heart tissue is in a hibernating state in which there are some cardiac cells, some blood vessel cells and some necrotic (dead or dying) cells. The stem cells isolated from adipose tissue, when introduced post-heart attack into the body, have been shown to reduce damage and become cardiac and blood vessel cells.
The ADSCs are able to promote the formation of new or regeneration of blood vessels because they secrete growth factors that stimulate survival and proliferation of blood vessel cells. These characteristics make the ADSCs an ideal cell therapy to stimulate the recovery of injured tissue and blood flow in lower limb ischemia and chronic heart ischemia patients. By directly injecting ADSCs into areas of low blood flow in the lower limbs or the heart, these regions can become populated with newly formed (angiogenic) cells, thereby improving blood supply.

Bioheart is currently establishing five Centers of Excellence in Latin America to provide its ADSC and myoblast cell therapies to patients suffering from congestive heart failure, chronic heart ischemia and lower limb ischemia. Bioheart entered into its first agreement with a leading treatment facilitator, Regenerative Medicine Institute of Tijuana, Mexico. Therapies for patients will be made available at the Hospital Angeles Tijuana, a fully equipped state-of?the-art private specialties hospital. This will be the first of five Centers of Excellence with four additional Centers to be announced in the coming months. The TGI 1200 Cell Isolation System is also currently being utilized in clinical studies to treat chronic heart ischemia in Venezuela and critical limb ischemia in the Czech Republic. A clinical trial for its use in treating acute myocardial infarction is planned.

Karl E. Groth, Ph.D., CEO
Dr. Groth became Bioheart?s Chairman and CEO in August of 2009. He has served as a member of our Board of Directors since January 2009. Dr. Groth is co-founder, along with Ms. Farley, of the Ascent Medical Technology Funds and since May 2000 has served as President and CEO of Ascent Private Equity, the General Partner of the funds, which are focused on investments in medical device, life science and biotechnology. Dr. Groth has over 30 years experience in the health care industry. He held management positions within Medtronic Inc. in research, product planning, marketing, and strategic business development from 1980-1989. From 1989 until 1999, he organized and served within executive management of a series of medical start-ups, all of which conducted successful initial public offerings followed by acquisitions by major medical companies. Dr. Groth received his B.S. from the State University of New York in biology, his M.S. in plant physiology from New York University and his Ph.D. in microbiology from the University of Minnesota. He has conducted post-graduate research as a Senior Scientist in the department of Laboratory Medicine at the University of Minnesota and published over 30 peer-reviewed articles in professional journals. In addition, Dr. Groth continues to publish and present on topics including vascular disease and endovascular intervention.

Peggy A. Farley, COO, CFO
Ms. Farley has served as a member of our Board of Directors since January 2007. Ms. Farley was appointed to our Board as a representative of Ascent Medical Technology Funds. Since January 1998, Ms. Farley has served as a managing director of the general partner and co-founder of the Ascent Medical Technology Funds. She is also the President and Chief Executive Officer of Ascent Capital Management, Inc. From 1984 until 1997, Ms. Farley was Chief Executive Officer of a set of firms that she developed as the locus for investment in the United States for non-US investors, engaging in venture capital investments, identifying and conducting acquisition transactions in the United States and South Asia as well as directing the management of private and corporate assets. From 1978 to 1984, she was with Morgan Stanley & Co. Incorporated, in the International Group of the Corporate Finance Division. Prior to joining Morgan Stanley, Ms. Farley served as consultant to U.S. corporations, including Avon, Ingersoll-Rand, Citibank, and Morgan Stanley. Her career in business began in the mid-1970s in Citibank's Athens-based Middle East and North Africa Regional Office. She received an M.A. from Columbia University in 1972 and an A.B. from Barnard College in 1970.

Kristin Comella
Ms. Comella was appointed as our Vice President of Research and Corporate Development in December 2008. Ms. Comella joined Bioheart in September 2004 and has played a major role in managing our product development, manufacturing and quality. Ms. Comella has over ten years of cell culturing experience including managing the stem cell laboratory at Tulane University's Center for Gene Therapy. Ms. Comella also developed stem cell therapies for osteoarthritis at Osiris Therapeutics. Ms. Comella holds an M.S. in Chemical Engineering from The Ohio State University.