It may be difficult to pronounce, but neurorestoratology is an emerging subdiscipline that emphasizes regeneration or repair of the damaged nervous system. IANR's mission is to pull together the pieces of research from around the world.
Attended by scientists from around the globe, the third annual meeting of the International Association of Neurorestoratology (IANR) took place April 23–25, 2010, in Beijing. The conference’s overall goal was to open-mindedly bring together divergent perspectives in an effort to accelerate the development of real-world therapies for a variety of neurological disorders, including spinal-cord injury (SCI), amyotrophic lateral sclerosis (ALS), stroke, and Alzheimer’s, Parkinson’s, and Huntington’s diseases.
Neurorestoratology is an emerging neuroscience subdiscipline that emphasizes regeneration or repair of the damaged nervous system. Its objective is the recovery of neural function lost due to trauma, neurodegenerative disorders/diseases, compromised blood flow, etc. Although many therapeutic strategies fall under the neurorestoratology umbrella, a key focal point has been stem-cell transplantation, a frequent topic in my Healing Options series for PN.
Believing that return of some life-enhancing function for many disorders once considered untreatable is now within our reach, IANR’s mission is to speed up the bench-to-bedside transition of basic-science laboratory research into beneficial clinical therapies, in part by pulling together the divergent pieces of the puzzle emerging throughout the world.
Recognizing that SCI bows to no flag, IANR believes its goals can be achieved through fostering better communication between world scientists. Indeed, I thought one of the conference’s greatest strengths was the opportunity to interact with scientists from Russia, China, etc., who often possess a different view on how to do things from many of my U.S. colleagues.
The driving force behind IANR’s creation was China’s Dr. Hongyun Huang, a pioneer in developing function-restoring, cell-transplantation procedures (PN, April 2004). Several senior scientists from throughout the world have assisted him in his IANR organizational efforts, including England’s Dr. Geoffrey Raisman, whose animal research laid the foundation for Huang’s procedures; Dr. Paul Sanberg, University of South Florida, one of America’s foremost stem-cell experts; and Dr. Ziad Mohammed Al Zoubi, president of the Pan Arab Spine Society and organizer of next year’s conference in Jordan.
(Due to space constraints, only a few presentations are summarized here).
■ Conference organizer Dr. Huang provided a big-picture overview of the nascent field of neurorestoratology, including some of the cell-transplantation programs emerging throughout the world, as well as key issues concerning and limiting their development. Although we have a long way to go before a true SCI cure, he emphasized neurorestoratology is bearing fruit now by providing some life-enhancing functional improvements.
Huang stressed that the needs of patients to have access to potentially beneficial therapies in a timely fashion should have greater priority. As such, we should more expeditiously and effectively translate basic-science discoveries into real-world clinical applications. Although ensuring scientific purity, our allegiance to an exacting scientific process often creates insurmountable barriers in getting treatments to patients.
Underscoring his belief, Huang quoted the 2000 Declaration of Helsinki (a policy delineating medical ethical principles):
“In the treatment of a patient, where proven prophylactic, diagnostic, and therapeutic methods do not exist or have been ineffective, the physician, with informed consent from the patient, must be free to use unproven or new prophylactic, diagnostic, and therapeutic measures, if in the physician’s judgment it offers hope of saving life, reestablishing health, or alleviating suffering.”
■ Dr. Sanberg (Florida) presented an overview of his stem-cell research focused on treating stroke and other neurological disorders. He suggested that aging, with its decline in regenerative ability, represents a stem-cell disease. With age, there is a diminution in number of stem cells and their potency. In this regard, Sanberg noted that one promising advance is the development of biopharmaceuticals that stimulate or help maintain our body’s stem-cell robustness as we age.
Because of the difficulty in the United States of using theoretically powerful but controversial embryonic stem cells, Sanberg focused his efforts on transforming uncontroversial, bonemarrowderived stem cells into neural progenitor cells for treating neurological disorders. Because readily available umbilical- cord blood is a good source of bone-marrowderived stem cells, he used it for his research.
Animal studies suggest these umbilical stem cells can, indeed, differentiate into neuronal stem cells with reparative potential in stroke. Injected intravenously, the cells appear to migrate to where they are needed and induce some behavioral recovery.
In an example of our need to pull together the puzzle pieces, Sanberg noted that certain drugs enhance the overall effectiveness of the transplanted stem cells. Given such findings, it is likely many future stem-cell therapies will be combined with an augmentative drug treatment. Indeed, this is the case for an ongoing SCI-focused clinical trial that combines umbilical stem-cell transplantation with lithium, a neuroprotective agent.
Sanberg also underscored that the time of stem-cell administration after neurological insult is a key consideration. If the cells are transplanted too early or late, efficacy will be compromised. He believes this is a good example of why we need a strong base of animal research before transitioning to humans.
This meeting's organizer, Dr. Hongyun Huang, is a pioneer in developing function-restoring cell-transplantation procedures.
Sanberg concluded with a thought-provoking discussion on the potential downside associated with the increasingly popular practice of quickly cutting and freezing the umbilical cord for future therapeutic needs. Specifically, if cord cutting is delayed, stem-cell-rich cord blood will be pumped into the newborn. Studies suggest this infusion enhances infant health. Sanberg noted that mankind has become the only species not allowing the transfer of cord blood into its newborns, which may have long-term, adverse consequences, especially for preterm infants. He ended with the observation that women in ancient cultures often gave birth while squatting, allowing the cord blood to flow into the newborn due to gravity. So to speak, umbilical-cord blood was “mankind’s first transplant.”
■ Dr. Adeeb Al-Zoubi (Jordan) [note: not the same Al-Zoubi as above], founder, Stem Cells of Arabia Network, and his colleagues have transplanted bone-marrow-derived, purified stem cells into ~50 patients with SCI. Isolated from the patient’s bone marrow (hence, minimal rejection potential), these cells were reintroduced into the patient’s spinal cord. Although some improvements were noted, he believes the results are “suboptimal.” As such, Al-Zoubi is researching ways to better prepare, process, and differentiate these and other bone-marrowderived cells into more neurologically oriented stem cells with, in turn, a greater potential to treat neurological disorders.
In reviewing various stem-cell programs emerging throughout the world, Al-Zoubi has observed that programs can be broadly assigned to three different operating models:
(1)With the classical scientific model, progress is slow and proceeds carefully, results are well reviewed and criticized by peers, and strong publications are produced. Usually, the major financial benefits accrue to biotech/drug companies, not the scientist.
(2) The opposite extreme is the aggressive model, in which there is little scientific basis, results are unknown, and there is an absence of publications; but the program is a moneymaker.
(3) The progressive model is between these two extremes. Although it takes advantage of the scientific process, it moves quickly to a patient-oriented disease/disorder-treating emphasis. However, because it generates a weaker foundation of publications, the program is often criticized.
■ Dr. Andrey Bryukhovetskiy is the director of Moscow’s stem-cell focused NeuroVita Clinic (September 2005 PN), as well as former chief neurologist, Russian Navy. His presentation focused on the epigenetic reprogramming of stem cells to increase their potential for treating neurological disorders. Basically, under epigenetic principles, we are not merely a hard-wired manifestation of our genetic DNA as once thought. The genes we express—and, as a result, who we become—is influenced by diverse environmental factors.
As discussed by Bryukhovetskiy, this epigenetic concept has great relevance for the development of stem-cell therapies. Basically, his overall goal is to epigenetically manipulate such cells to turn them into more regeneratively robust cells better tailored to treat specific neurological disorders.
As part of his efforts, Bryukhovetskiy encapsulates growth-influencing factors within tiny biodegradable nanocapsules. These will be incorporated into the stem cells isolated from the patient. After transplantation back into the patient, the nanocapsule-containing stem cells will migrate to the dysfunctional area. Eventually, the nanocapsules will biodegrade, releasing the growth-influencing factors. Depending upon their specific nature, these factors should steer the neighboring dysfunctional tissue in the desired direction—e.g., perhaps regeneration or, in the case of tumors, cell death.
Energy-based therapies represent another intriguing piece of the restoration puzzle. For example, numerous studies suggest laser therapy has a neuroprotective effect, preserves injured nerve functional activity, decreases injury-site scar tissue, lessens degeneration in corresponding motor neurons of the spinal cord, and increases axonal growth and insulating myelin.
Developed by France’s Albert Bohbot, Laserpuncture combines elements of laser therapy and acupuncture, both of which influence the expression of regenerative stem cells.
A number of stem-cell recipients with SCI have attempted to maximize restored post-transplantation function with Laserpuncture. Bohbot’s presentation specifically focused on the improvements, as measured by electromyography (electrical recording of muscle activity), of three individuals who underwent Huang’s cell-transplantation procedures. Huang uses olfactoryderived cells that have been shown to promote axonal regeneration by (1) producing insulating myelin sheaths around growing and damaged axons, (2) secreting growth factors, and (3) generating structural and matrix macromolecules that lay the tracks for axonal elongation. Bohbot’s results suggest the Laserpuncture/cell transplantation-combination therapy restored some voluntary muscle activity. This is a good example of the sort of pulling-together-of-the-pieces effort we need.
I provided an overview of my extensive database of diverse therapies that have the potential to restore some function after SCI. Developed with the patronage of Iceland’s Institute of Spinal Cord Injury, the information has been posted in five languages (English, Spanish, Chinese, Russian, and Arabic) on www.sci-therapies.info (see also www.isci.is).
The Paralyzed Veterans of America (PVA) has tentatively agreed to publish the database as a book. The foreword to this resource was written by former Iceland President Vigdis Finnbogadottir. In addition to defining the project in an all-inclusive fashion that resonates with IANR goals and objectives, she placed its mission within a human-rights context.
One of bustling Beijing’s most serene places is its Buddhist temple. As I contemplated this meeting, the temple reminded me of Buddha’s philosophy to pursue a not-too-rigorous or -lax spiritual practice in quest for enlightenment, but rather the “Middle Way.” As implied by many conference speakers, we need some sort of “Middle Way” for developing new function-restoring therapies.
On one hand, some exceedingly scientifically lax stem-cell programs have emerged throughout the world—seemingly developed to merely financially exploit the desire of people with SCI to access the promise of stem cells. On the other hand, the daunting U.S. scientific standards, molded by well-meaning policies of the Food and Drug Administration (FDA) and National Institutes of Health (NIH), both of which are my former employers, will guarantee that few stem-cell therapies will be forthcoming, especially for a disorder like SCI with a limited economic market. If we are truly going to generate new therapies, especially those harnessing the very real power of stem cells, in a timely but reasonably scientific fashion, we need to find the “Middle Way.”
A Matter of Human Rights
“…The cornerstone of this Icelandic-sponsored project is a belief that if we can open-mindedly integrate the divergent pieces of the puzzle that exist throughout the world—whether they originate in the U.S., China, Russia, etc., whether they reflect the perspectives of Western or Eastern medicine, or whether they reflect the contributions of large medical centers or small clinics, restoration of function after SCI is a real-world possibility now and not just some distant, elusive possibility. Given this belief, this database of therapies pulls together for the first time a discussion of many of these divergent pieces within one resource. I believe, however, that the amazing
SCI-related medical and scientific advances of recent years should be considered within a more expansive human-rights context. Specifically, these advances represent one mechanism by which people with SCI can be meaningfully integrated into society and enjoy mankind’s most fundamental freedom of self-determination. The overall goal of today’s exciting breakthroughs should not be viewed as making one whole again because the spirit is always whole. The goal is empowerment, freedom of self-determination, and the ability to manifest the spirit within….”
—Vigdis Finnbogadottir President of Iceland, 1980–1996