Transmyocardial revascularization and autologous stem cells

Among the wide range of options that are available or under development for the treatment of coronary artery disease, one that has not drawn a great deal of attention is transmyocardial revascularization (TMR).  In TMR, a laser is use to drill multiple (15-40) millimeter sized channels through the myocardium in order to increase blood flow for patients with angina who may not be good candidates for bypass grafting. 

Two systems have been approved by the FDA for use in the U.S., an Ho:YAG laser system by Cardiogenesis and a CO2 laser system by PLC Medical Systems.

The principal reason that TMR has not drawn much attention, coincident with the small number of FDA approvals, is the lack of good data demonstrating the direct benefit of TMR in relief of angina.  Indeed, some cardiologists suggest that any benefit of TMR in in relief of angina is either due to denervation of the tissue or a placebo effect (Allen et al; Anesthesiology Clin 2008;26:501–519).  However, five-year follow-up data (which take some of the steam out of placebo benefits), suggest that the channeling does indeed increase vascularization and associated benefit in both angina and perfusion.

A paper was presented at the 2009 European Society of Cardiology Congress on the use of PLC Medical Systems’ CO2 TMR laser in conjunction with autologous stem cells.  As described in The Medical News:

This study is designed to examine the safety and feasibility of transplanting stem cells during TMR used in combination with coronary bypass grafting in patients with end-stage heart failure. According to the initial results of the study, this procedure was effective in improving cardiac function, as assessed by echocardiography and magnetic resonance imaging prior to therapy and post surgery, as well as three, six and twelve months afterwards. In addition, the treatment thus far has proven feasible and safe; no intra- or post-operative major adverse cardiac events occurred in the patients enrolled in the study.

The great majority of treatments for ischemic heart disease are alternatively addressed by coronary artery bypass grafting (CABG) or the use of angioplasty, typically with stenting (most often with drug-eluting stents).  TMR represents a unique technology that may, alone or even in combination with CABG or with, as described above, the use of autologous stem cells, provide clinical benefit for a subset of patients whose ischemic heart disease contraindicates CABG or angioplasty/stent alone.

The MedMarket Diligence report #C245 addresses the "Worldwide Market for Drug-Eluting, Bare Metal and Other Coronary Stents, 2008-2017."

 

Growth and penetration of drug-eluting, bare metal and absorbable stents

Currently, the market penetration for drug-eluting stent (DES) devices ranges in the neighborhood of 60% (as high as 90% in China) and is growing at more than 7% per year worldwide. By comparison, the worldwide market for all coronary stents is currently growing at nearly 6% while the market for bare metal stents (BMS) is growing at 3% per year. Compounded annually from 2008 to 2017, the market for all coronary stents is growing at 5.3%, DES at 4.4%, and BMS at 1.6%.

The market for fully biodegradable, absorbable stents is not likely to emerge until 2013-2014. Because study results so far have shown the leading absorbable stents to hold great promise in effectively treating atherosclerosis, growth rates are expected to run well into the double-digits, forecast to grow at compounded annual growth rates in the neighborhood for 15%–20% for the first five years or more.

The relatively brief history of coronary artery disease treatment, even including surgical intervention via CABG, has demonstrated that it has a remarkable propensity to evolve in surprising ways.  Surgical intervention, percutaneous intervention, the stent and drug-eluting stent solution to restenosis, the emergence of multiple invasive yet still surgical interventions, drug-coated angioplasty balloons, atherosclerotic plaque-reducing drugs, gene therapy, cell therapy…

The most forward-thinking competitors in the market for coronary artery disease (CAD) treatments have planned obsolescence in mind, whether they wish to or not.


The worldwide coronary stent market, and its larger CAD market, is part of Report #C245 from MedMarket Diligence.

 

Coronary stent types: drug-eluting, bare metal, others

 
In our May 2009 report (#C245) entitled, "Worldwide Market for Drug-Eluting, Bare and Other Coronary Stents, 2008-2017," we assess the current state of technology and product development, current and forecast markets, market shares and the manufacturer opportunities for all stent types used in the treatment of coronary artery disease (CAD).

Types of Coronary Stents and Selected Other Anti-Restenosis Devices

stent-types-with-examples

 Source: MedMarket Diligence, LLC, Report #C245.

 The report also provides a valuable context for the coronary stent market — the range of non-stent alternatives for treatment of CAD, including open and minimally invasive coronary artery bypass grafting (CABG), drug-eluting balloons, HDL therapy, gene therapy, cell therapy and others.

Artificial pancreas for type 1 diabetes

Discussed in a press release from the University of Virginia Health System, "Aritificial Pancreas Proves Effective in Treating Type 1 Diabetes Overnight in Pilot Study."

Researchers at the University of Virginia Health System are reporting remarkable results from their pilot clinical study of the artificial pancreas, a computerized, subcutaneous system that could one day revolutionize the way Type 1 diabetics manage their disease.

The system, which uses an individually-“prescribed” control algorithm to regulate blood glucose levels, achieved excellent overnight control of glucose levels in Type 1 diabetics and a five-fold reduction of hypoglycemia. A condition produced by lower than normal blood sugar levels, hypoglycemia can result in coma, seizures and even death.
 

Several years ago, while attending a pediatric diabetes association (PADRE) retreat, I spoke with a lead researcher from UCSF (I am scouring past files to find his name) regarding the prospects for pancreatic cell transplants for the treatment (reversal?) of diabetes.  The answer, from a researcher who focuses on cell transplant therapies, surprised me and that was that the most practical solution to diabetes, one not likely to be bettered for a long time to come, was going to be an artificial pancreas of the type described above in which a glucose meter is linked in a biofeedback system to an insulin infusion pump.  The reason this surprised me was that, in my idealistic view of biotechnology in general, and cell therapy specifically, the use of devices was always going to be imperfect compared to the "pure" solutions possible (aka "rational therapeutics") from the biotech arena, since biotech solutions are often focused (via cell therapy, gene therapy or other disciplines) in effectively reversing the root cause of a particular disease, rather than on addressing symptoms alone, even comprehensively. 

However, as elaborated by the UCSF researcher, cell therapy is already available, but is encumbered by (among other things) the need for expensive and side-effect-plagued anti-rejection drugs.  Even the advent of autologous stem cells (which would theoretically avoid immunogenecity problems, since the cells transplanted are patient’s own) is not practical solution compared to a biofeedback device, since the hurdles to sctem cell transplantation have provide to higher than anyone anticipated.

Having focused on the medical device arena and having harped on previously about this idea that there is the "ideal" biotech solution that may never come while the "here and now, treat the symptoms effectively" solution of the device arena can be so pragmatic (and sustains big medtech markets), I am eminently sensitized to the polemic between the two.

The UVHS development is a practical demonstration that the technical hurdles of providing a relatively simple system of a biofeedback device for blood glucose regulation through insulin infusion are dramatically less challenging than cell therapies.

Having said this, I can still be comfortable in the notion that one day a cell therapy, or a gene therapy or some other "rational therapeutic" will be developed that can cure each case of diabetes in a practical, affordable way.  Until then, I am exceedingly pleased to know that medtech development is capable of getting the job done now.


The author has someone very close to him who has Type 1 diabetes.

Cell therapy in treatment of osteoarthritis

The applications for cell therapy (stem or otherwise) continue to expand in very diverse ways.

I found this development particularly interesting — the use of stem cells in a "cell bandage" for use in the treatment of osteoarthritis. The company is Azellon, Ltd. 

azellonProf Anthony Hollander from the University of Bristol in the UK, has been busy recently, raising over £1.6 million (US$2.3 million) to fund trials, including the first human study, of "cell bandage" technology. The latter aims to save thousands of patients from the type of knee surgery that currently leads to premature osteoarthritis (OA). 

See Azellon Ltd.

 

Common threads in new medical technology development

In a prior post, I highlighted the technologies that are the focus of startups we have identified since early 2008.   Within the boundaries of what we focus on in our search for startup companies — device companies and those that are either complementary to or competitive with device companies — there is a pretty significant variation.  Nonetheless, there are some common themes, which we have seen previously (see our white paper), on the types of technologies that represent growth opportunities for specific reasons.

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Here are some of the common threads:

  • Cardiovascular.  The cardiovascular arena has long been a source of much medical technology development, since many of the problems can be treated (if not solved) by devices — angioplasty, stenting, valves, vena caval filters, anti-arhythmia devices.  There are also well-established, FDA-approved technologies on the market, which enable sometimes only relatively modest technology advances to represent new business opportunities.
     
  • Minimal invasiveness.  If a patient can be treated with less trauma, even if only nominally, it is well received in the marketplace for the presumption of improved quality of life, better clinical end-point, etc.
     
  • Neurology/Neurosurgery.  The brain and nervous system have of late been rapidly giving up secrets of their normal function as well as pathology.  This has given support to aggressive efforts to develop treatments where, in some cases, none have existed previously. The neurology area represents a true new frontier for much new medical technology.
     
  • Pain management.  As a result of physicians historically addressing pain as an unfortunate side-effect of trauma and disease, rather than a more direct problem to be dealt with, pain has not represented a significant area of attention for either medical school curricula or medtech development — until recently.  Many medical schools now provide programs focused on the problems of pain management as unique medical issues to be addressed specifically. (Interestingly, a common area of "pain management" technologies is focosed on back pain — whether from spine surgery or trauma — and pain, rather than the trauma or disease, is communicated by the companies as being the a priori target of development.)
     
  • Cell and tissue engineering.  Options to address disease and trauma with a variety of cell and tissue solutions are becoming commonplace in areas long the focus of medical device and drug technologies.  Even without the advent of stem cell technologies (and its commensurate tendency for hyperbole), cell biology has advanced to the level of very effective clinical science.  As device makers consider their competition (or potential partners), it is unwise to ignore cell/tissue therapies.
     
  • Materials technologies.  Devices are no longer simply inert plastic or metal (indeed, it has become clear that they never were truly inert).  The variety of materials under development, on their own or in conjunction with coatings or other configurations, reflect a growing recognition of the need for materials to perform far more than structurally, as dynamic products that even evolve (or dissolve) during their product life to improve clinical performance.
     
  • Nanotechnologies. Not to be entirely disassociated from the above discussion of materials technologies, nanoetechnologies (and their larger counterpart, microelectrical machine systems or MEMS) are a promise-filled set of innovations (with actually little in common other than size) that have begun performing extraordinary clinical activities. Science continues to evolve, so as much as these technologies may have already (over)promised their potential, the bar will continue to be raised as phenomenal developments are made and commercialized.

I have not touched on all of the common themes, but these are ones I see again and again, particularly for their ability to drive the imaginations of entrepreneurs.

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See our Reports, which address many of these threads.

Stem cell / gene therapy success in vitro

Researchers at the Salk Intitute for Biological Studies have demonstrated that a technology to correct the genetic defect in human disease and induce cell differentiation at the site of the manifested disease is feasible, an achievement demonstrated previously only in mice.
 
In the May 31, 2009, edition of Nature, Salk reseachers published their findings for the research, which applied the method to a blood-related disorder called Fanconi’s anemia. (See "Combined stem cell-gene therapy approach cures human genetic disease in vitro" at link.
 
This development, although still only at the in vitro stage, is a remarkable one, since it demonstrates a synthesis of understanding between genetics and cell biology that is a harbinger of tremendous future clinical successes. But, lest the jaded investor or other biotech follower (who has countless times heard in vain of similar portentous milestones) fear that this, too, is a development that is of only passing significance, it should be noted that this development bears greater impact due to the level of science demonstrated and that it has been made by Salk Institute and published in Nature, neither of which should be underestimated.
 
Personally, whenever I note a development that has both "gene therapy" and "cell therapy" in the title, my senses are alerted to the great prospect (not guarantee) of what will follow.
 

Posted via email from medmarket’s posterous