The Power to Heal Comes from Within

Powerful chemical weapons, also known as drugs, and sophisticated surgical procedures have dominated the practice of medicine for many decades.  For at least the last 15 years, maverick researchers and physicians have been exploring biologic alternatives to drugs and surgery.  Instead of searching the world for a novel chemical compound or engineering a sleek surgical device, they have looked in an unusual place--inside the body itself.  Could it be possible that the power to heal comes from within our own bodies?  The answer today is a qualified yes.  

Think about it for just a moment.  Next time your get a small paper cut, simply observe what happens.  You bleed a little.  It stops on it own.  You put a bandaid on it and magically it heals over the course of less than a week.  Similarly, if you sustain a simple fracture, it typically heals on its own with immobilization and a few weeks of time.  Your liver is your most amazing regenerative organ.  You can literally cut out a lobe of your liver and transplant it into someone else.  That missing lobe will then regrow on its own.  Skin, bone and liver are tissues that have excellent capacity to self heal. Other tissues need a helping hand.  Fortunately, within our own bodies are many tissues that can help heal other tissues.  Blood, bone marrow and adipose tissue (also known as Fat) are three examples.

To begin, let's explore platelet rich plasma, also known as "PRP".  PRP is a component of blood that can be prepared using a simple desktop sized centrifuge in about 10 minutes.  I have using PRP to treat chronic tennis elbow now for more than a decade with excellent success rates.  Multiple studies now confirm the value of PRP in the treatment of this common disorder.  A recent meta-analysis of randomized controlled trials noted PRP to be "of great clinical significance."  PRP has also been used to treat diabetic foot ulcers, knee arthritis and degenerative disc disease.  Overall, there are now more than 8600 published studies evaluating the basic science and clinically efficacy of PRP.   Importantly, in all of the areas studied, PRP has an excellent safety record.  That of course makes sense.  PRP is simply a component of your own blood.

Cancer immunotherapy is another example of using your body to help heal itself.  Cancer immunotherapy essentially reprograms your immune system to help fight nasty cancers.  Recently published data has found an "unprecedented" 94% of patients with a specific type of blood cancer achieving complete resolution of their symptoms.  The technique involves removing your own white blood cells, reprogramming them to attack tumors in the lab and then injecting them back into your body.  To quote one researcher, "This is really a revolution."

Finally, a therapy that sounds like it came out of a science fiction or horror movie is just beginning.  The idea of parabiosis involves merging the circulation of two animals.  The original research was done in young and old rats in 1956.  For the details please review a tantalizing paper entitled "Experimental Prolongation of the Life Span (Ref 1)  When their circulations were connected, the young mice started becoming "old" and the old mice started to appear "young".  Something in the blood of young mice was helping reverse the affects of aging in older mice.  The coats of the old gray mice were turning brown again.  Other research conducted at Stanford suggested young blood could boost brain cell growth in older mice.  (Ref 2, Ref 3 Ref 4)  This research was so intriguing, it led to the development of a clinical trial focused on the transfusion of young blood to older patients with Alzheimer's disease.   Silicon Valley tycoons are also helping finance similar "treatments" for middle aged rich people who want to stay young or reverse the affects of aging.  A company has even been started and is presently conducting clinical trials.  Interestingly, the company is named Ambrosia after the mythologic Greek drink that was supposed to confer longevity or even immortality.  Peter Thiel, an iconoclastic venture capitalist , appears to be quite interested in this approach to combating the aging process.  This approach is clearly not yet proven but is intriguing.

If we are seeking transformative solutions to difficult problems, I suggest we look inside.  We might just find the power to heal.

Allan Mishra

Improve how your DNA works by Riding an Exercise Bike

The Epigenetics of Exercise

Allan Mishra, MD

You can’t change your DNA but you can change how it works. DNA is the coding program for all of the enzymes and proteins that make your body function. 

Epigenetics is a rapidly evolving area of science that studies how modifications on or around your DNA alter the production of specific molecules. Your DNA is fixed but how it works is affected by the proteins and chemical groups that surround the famous double helix.  You can think of epigenetics as variable signposts on the winding tracks of your DNA that either suppress or promote specific genes.  The proteins and chemical groups have fancy names like a “histone” or a “methyl group”.  These "epigenetic" markers don’t change your DNA but rather change how it interprets the underlying genetic code.  They can turn on or off a section of DNA and dramatically affect YOU.  The science is called “Epigenetics” and in 2015 and beyond, it will alter the way we all approach medicine and wellness.  Multiple articles about epigenetics have appeared in Time Magazine, the New York Times and many other elite publications.

Exercise is one way you can change how your DNA expresses itself via epigenetics in a positive fashion.  A recently published study required people to ride an exercise bike with one leg for 45 minutes four times per week for three months.  Before and after the exercise trial, the subjects had a muscle biopsy of both legs.  The researchers found "health enhancing adaptations" were induced by the "physiologic stimulus" of riding an exercise bike via epigenetic mechanisms in the leg that did the pedaling but not in the one that did nothing.  (Ref: Lindholm et al 2014)  The results are meaningful for anyone who wants to stay in shape and be active.  Importantly, the inherited proportion of physical performance has been shown to be about 50%. Therefore, about 50% of overall physical performance is dependent upon training and lifestyle.  (Ref:  Ehlert etal 2013)  This means that we are at least partially in control of how our bodies work and perform.  We can't blame all of our health problems on bad genes.  

Exercise has also been found to have positive effects on the central nervous system, the  cardiovascular system, the aging process, the prevention of type 2 diabetes and the prevention of cancer all via epigenetic mechanisms.  (Ref:  Ntanasis-Stathopoulos et al, 2013)

So, dust off the exercise bike in the garage, make time in your schedule to get to the gym, or join Soul-Cycle in 2015.

Specific immediate action items:  Consider starting your exercise routine with QuadCrunches and Hamstring Stretches.  They are simple exercises that can be done anywhere.  For the bike, try 20-30 minutes 3 times per week with moderate resistance.

Remember, exercise can literally change how your DNA functions and potentially save your life.

AM

TotalTendon

ALWAYS consult your own physicians before beginning any exercise program.

Will Kobe Bryant go to Japan to Treat his Knee Arthritis?

Japan Accelerates Regenerative Medicine with Regulatory Reforms

Why the United States Must Follow Their Lead

Sign the online petition supporting Regenerative Medicine

Kobe Bryant, an elite professional athlete from the National Basketball Association’s Los Angeles Lakers, has gone to Germany multiple times to be treated with a portion of his own blood for his creaky, arthritic knees.  The reason why he went to Germany is simple.  He wanted to have the best chance to play at the highest level in the NBA and he had exhausted all his options in the United States.  He went there to be treated with a component of his own blood that targets the inflammation associated with knee osteoarthritis.  The treatment he received is not approved here in the United States. 

Will he go to Japan next time to get the most advanced therapy?  That may happen because in November 2014 Japan enacted legislation creating a new pathway that accelerates the approval process for regenerative medicine products.  We here in the United States need to figure out how to best accelerate our own regenerative medicine efforts or continue to watch our elite athletes and other patients seek treatment beyond our shores.  Let’s explore why Japan acted boldly in favor of regenerative medicine. 

A Nobel Prize was awarded to Japanese researcher and former orthopedic surgeon, Dr. Shinya Yamanaka in 2012 for his pioneering work on how to reprogram mature skin cells into pluripotent stem cells.  His potentially life saving work and the national pride associated with it helped Japan become a worldwide leader in stem cell research.  Importantly, Japan has also prospectively pursued and passed legislation that will dramatically stimulate regenerative medicine.  The country took a leap into a bright future last week with the implementation of regulatory reforms directed at accelerating the development of cell-based treatments. 

The new law established a separate pathway for regenerative medicine products apart from traditional drugs and medical devices. The regulations also created a system that fosters faster commercialization of novel biologic products and can lead to time limited approvals for up to seven years.   Post market data analysis will continue to confirm the safety and efficacy of the regenerative medicine products with the potential to revoke approvals. 

The action by the Japanese government creates the proper equilibrium between the need for accelerated approvals for cell based therapies that have established efficacy while ensuring product safety.  The typical phase one, phase two and phase three trials for new drugs are not a proper pathway for cell-based therapies that have highly complex mechanisms of action that may or may not be identified even with elite preclinical models.  Importantly, many cell-based products come directly from a patient’s own body and therefore have a dramatically higher safety profile. 

Americans are screaming for new treatments for a variety of difficult problems such as arthritis, heart disease and diabetes.  Regenerative medicine and especially cell-based treatments have a chance to help treat and potentially cure these problems.  We need to follow the Japanese lead and create similar pathways in the United States.  Last year during a visit to Japan and its PMDA (the equivalent of the FDA), I was staggered by how engaged they were about regenerative medicine and receptive they were to understanding how to bring safe and effective biologic products to their populace.

The United States can learn a great deal from Japan’s enlightened approach to regenerative medicine.  Safety of course should be paramount.  The idea of a conditional, time-limited approval with reimbursement strikes a perfect chord as we seek better treatments for our patients at more affordable prices.  Competition will arise to obtain approvals based on phase two trials that confirm safety and show a solid degree of efficacy.  Importantly, more competition will lead to better options and faster innovation similar to the computer industry over the last several decades. 

We need to also emulate our Silicon Valley technology colleagues and call for a Medical Moore’s Law.  Identify a specific clinical problem, create a novel solution and within five years double the efficacy and decrease the price by fifty percent.  Data analysis via powerful graphical algorithms should assist with new discoveries and also help with better management of many diseases.  

We must seek dramatically higher horizons instead of being satisfied with iterative improvements.  The Japanese government should be congratulated for passing regulatory reform and implementing transformative solutions.  Sooner, not later, we need to find ways to execute our own regulatory reforms here in the United States to help our patients and to remain competitive on the world stage in regenerative medicine.

Perhaps, then Kobe will be treated in California instead of Germany or Japan.

Allan Mishra, MD

TotalTendon


Sign the online petition supporting Regenerative Medicine

Please post any comments or suggestions about how to safely accelerate regenerative medicine.

References

(http://www.nobelprize.org/nobel_prizes/medicine/laureates/2012/yamanaka-facts.html)

Accessed 11/30/14

http://www.pmda.go.jp/english/events/2014taiwan_sympo/14_Keynote1.pdf

Accessed 11/30/14

Proposition 46 Jeopardizes California Medical Excellence

California offers its citizens excellent health care.  It has over 100,000 hard working physicians dedicated to taking superior care of their patients in conjunction with well-trained nurses, medical assistants, technicians and support personnel. (Ref)  According to US News and World Report, 17 of California's hospitals are nationally ranked in specialities such as oncology, cardiology and orthopedic surgery.  Fifty-six other hospitals meet standards for strong performance within the state. (Ref) 

Proposition 46 is a direct threat to our superior California healthcare.   It would undermine a physician’s ability to best care for patients and result in dramatically higher costs—$9.9 billion annually according to one study (Ref)   Doctors already concerned about malpractice would face increased pressure to practice defensive medicine.  If this measure passes it will also be difficult to recruit and retain specialists who are in high risk specialties including OB/GYN, trauma surgery and neurosurgery. 

Proposition 46 further creates a disincentive for physicians to implement novel solutions to challenging diseases.   Medical innovation is needed to attack arthritis, cancer, diabetes, and the emerging Ebola epidemic.  If Proposition 46 passes, physicians will be less inclined to pursue new transformative solutions for fear of being sued and medical innovation will stall.  Instead of California physicians and hospitals being recognized as worldwide leaders in medicine, we may no longer be able to offer patients cutting-edge care within our state.   

Unfortunately, many Californians are unaware of the significant issues that will arise if Proposition 46 passes.  Over the past several months, I have had discussions with dozens of people about 46 and have been surprised at how little they know about this onerous proposition.  Their lack of awareness is frustrating because the trial lawyers completely understand the implications of the proposition they drafted.  As we approach the upcoming election, I strongly urge California residents to read and analyze proposition 46.    Prop 46 Info

One concern imbedded in the proposition that should be addressed is the need to curtail multiple prescriptions from being written and filled by deceptive patients.  The solution to this problem is not to pass the three-headed monster known as Proposition 46.  The better answer is to improve tracking technologies such as CURES that eliminate duplicate prescriptions from being ordered or filled at a pharmacy and at the same time increase the criminal penalties for patients that fraudulently try to  

obtain multiple narcotic prescriptions.

If you wish for California to maintain its worldwide leadership in the delivery of outstanding medical care, I urge you to Vote NO on Proposition 46.

Allan Mishra, MD

Some thoughts on the Future of Medicine

Genome data interpretation will emerge as its own medical specialty much like radiology for evaluation of xrays, CTs & MRIs.  It will take some time but the complexity of the information will eventually lead to a board certified specialist that helps primary care doctors understand genetic tests.  

Transformative solutions more often arise via iconoclastic horizons not via the cognoscenti.  Translation:  Truly significant advances do not arise from established ideas and people.   They destroy established ideas and patterns of behavior.  


"Citizen Scientists" and "Health Hackers" Conducting trials, analyzing data and presenting papers.   How can we all help in the advancement of science:  
http://online.wsj.com/article/SB10001424052970204621904577014330551132036.html

Tumor Treating Fields (electrical current) used to treat brain cancer. 1st prescription patient. Novel GBM treatment

http://medicalxpress.com/news/2011-12-patient-prescription-fda-approved-brain-tumor.html

Stem Cell Types

There are three basic types of stem cells. Embryonic stem cells as the name implies come from embryos and have ethical issues surrounding them. Adult stem cells can be purified from a variety of sources including bone marrow and fat. Finally, induced pluripotent stem cells are artificially made from somatic cells such as skin cells. This final type of stem cells is produced by a form of genetic engineering. Viruses are used to insert genes and change the characteristics of the cells.

Embryonic and induced pluripotent stem cells are years away from any real value as treatments because they carry a serious risk of cancer. This has not been well outlined in the press but needs to be discussed. Adult stem cells are used for a variety of treatments already including bone marrow transplants and other indications.