Sent: Sunday, October 09, 2005 2:53 PM
Subject: Russian Stem-Cell Therapy


HEALING THERAPIES NEWSLETTER
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This is the 20th email newsletterC associated with
www.healingtherapies.info. The purpose of this website is to expand the
healing spectrum of people with physical disabilities, especially spinal
cord dysfunction. Newsletter size (~3,700) precludes responses to individual
inquiries. [To unsubscribe, respond with "delete."].

This newsletter discusses an innovative stem-cell program for spinal cord
injury developed by the NeuroVita Clinic, Moscow, Russia under the direction
of Dr. Andrey Bryukhovetskiy.

Please support those who have made this newsletter possible, including
"PN/Paraplegia News" (subscribe 602-224-0500 or www.pn-magazine.com), and
the Paralyzed Veterans of America (www.pva.org).

Demos Medical Publishing is publishing my book "Alternative Medicine and
Spinal Cord Injury: Beyond the Banks of the Mainstream." Although this book
will benefit virtually anyone who wishes to learn more about alternative
medicine, it especially targets people with SCI, their families, friends,
caregivers, and health-care providers. In addition to wellness-enhancing
alternatives, the book provides information about healing modalities that
have the potential for some individuals under certain circumstances to
restore some appreciable, quality-of-life enhancing function. The book can
be ordered at www.demosmedpub.com/book181.html or www.amazon.com.
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RUSSIAN STEM-CELL THERAPY
(adapted from September 2005 "Paraplegia News" article)

We are a part of a global community in which the devastation of spinal cord
injury (SCI) bows to no flag, and solutions will not be any country's
exclusive domain. Integrating the diverse pieces of the puzzle necessary to
develop real-world solutions requires that we open-mindedly work in
cooperation and not in competition. With such cooperation, restored function
after SCI will be a coalescing reality and not just a never-ending, elusive
pie-in-the-sky dream. 

In this spirit of bridge-building, I recently traveled to Moscow, Russia
where I became the first American scientist to check-out an innovative
stem-cell program for SCI developed by the NeuroVita Clinic under the
direction of Dr. Andrey Bryukhovetskiy. His work is especially important
because few scientists have accumulated as much hands-on experience as he
has in treating human SCI with stem cells, an approach many experts believe
will play a key therapeutic role in the future.
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THE SCIENTIST:
I'm always amazed how good often emerges from the tragic. For example, the
Paralyzed Veterans of America (PVA), whose programs have benefited so many
with SCI over the years, was born out of World War II's violence.
Bryukhovetskiy's promising stem-cell therapies also grew out of a desire to
help paralyzed veterans, in this case, those who sustained injury in
Russia's Afghan and Chechnya military conflicts.

He is a veteran, specifically a 45-year-old retired Colonel who once
directed the Russian Navy's neurology department. Because of his
long-standing empathy for paralyzed veterans, Bryukhovetskiy expressed a
desire to collaborate with US veteran organizations, such as PVA, to
accelerate the development of real-world SCI therapies.

Bryukhovetskiy is a charismatic leader passionately committed to his mission
and patients. His work in humans is built upon a strong foundation of
research using a variety of SCI animal models. Because much of his research
has been published in Russian, it is not well appreciated in the world's
English-emphasizing scientific community. As seems to be the case for so
many innovators regardless of country, he has often struggled to carry out
his pioneering research because the vision behind it runs counter to more
entrenched perceptions of what is possible after SCI.

Reflecting Hippocrates' ancient wisdom "that natural forces within us are
the true healers of disease," Bryukhovetskiy told me that stem cells "are
the medicine within us."

In 2002, Bryukhovetskiy established NeuroVita, a state-of-the-art, private
clinic that treats a variety of neurological disorders. The clinic occupies
several floors in a wing of the massive N.N. Blokhin Russian Cancer Research
Hospital Complex five miles southeast of downtown Moscow.  Staff includes
numerous physicians and rehabilitation specialists, and has access to the
expertise of nearby hospital scientists. Although to date patients have been
treated under an official scientific research protocol, soon after my visit,
the Russian Health Ministry authorized the use of Bryukhovetsiy's stem-cell
technology for general clinical practice.
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TRAVEL:
My trip to Moscow went through ten time zones, taking several days for my
luggage to catch up. Because of jet lag and Moscow's "white nights" near the
summer solstice, it was difficult to sleep at night but nodding off in the
day was common. During my visit, I stayed in clinic-affiliated lodging.
Although few understood English, and the Russian Cyrillic alphabet makes
understanding even more challenging, I was able to get around with relative
ease, e.g., take the subway to the Kremlin and Red Square, go to the market,
etc.

As a reflection of our emerging global community, television showed, for
example, American sitcoms and Arnold Schwarzenegger movies dubbed in
Russian, as well as rock videos featuring Britney Spears, unfortunately
still in English. Although I was unable to talk to waiters, American rap
music was often loudly played in the background. Fortunately,
Bryukhovetskiy's assistant Maria Zhukova, a former English teacher, provided
excellent translational assistance.
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TRANSPLANTED CELL TYPES:
Stem cells are progenitor cells that have the potential to differentiate
into a variety of cells that theoretically can treat various neurological
disorders. Bryukhovetskiy has used both embryonic/fetal and adult stem
cells.

Although embryonic/fetal stem cells have the greatest potential to mature
into a variety of cell types, they are controversial, and it is difficult to
direct their differentiation pathway.

Adult stem cells are found in many tissues, including bone marrow, which
produces, for example, hematopoietic stem cells that give rise to blood
cells, and nervous tissue, whose stem cells can evolve into neurons and
neuronal support cells (i.e., glia). Although adult stem cells usually
differentiate into the specialized cells associated with the originating
tissue, when certain micro-environmental cues are provided, they can mature
into cells associated with other tissue. For example, under appropriate
circumstances, bone-marrow-derived stem cells have the potential to become
nerve cells.

Certain drugs stimulate the bone-marrow to produce more stem cells, which
then spillover into the blood, where they can be collected.

When the patient is the source of the cells (i.e., autologous), there is no
immunological rejection when they are re-introduced. In contrast,
embryonic/fetal cells represent different genetic material (i.e.,
allogeneic) and have rejection potential, although to some degree their
undifferentiated nature helps minimize this risk.

Bryukhovetsiy no longer uses embryonic/fetal stem cells due to the ethical
controversy surrounding their use, their rejection potential, and, most
importantly, his belief that autologous, adult stem cells are more
effective.

In some patients, Bryukhovetskiy has transplanted autologous olfactory
ensheathing cells (OECs) using procedures developed by England's Dr.
Geoffrey Raisman. Although not technically stem cells, OECs have
considerable regeneration potential and have been the focus of much
attention in the SCI research community. When OECs are transplanted into the
injured spinal cord, scientists theorize that these cells promote axonal
regeneration by producing insulating myelin sheaths around both growing and
damaged axons, secreting growth factors, and generating structural and
matrix macromolecules that lay the tracks for axonal elongation.
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ASSESSMENT PROCEDURES:
Improvement was evaluated using a variety of assessment procedures,
including the commonly used ASIA (American Spinal Injury Association)
impairment scale in which grade A and E represents the most and least severe
injury, respectively. Although this scale is frequently used, experts
emphasize it is often insensitive to small but significant functional
improvements. Bryukhovetsiy has noted this insensitivity in his research;
i.e. some of his patients with very real life-enhancing improvements did not
improve their ASIA grade. Other measurements included FIM (Functional
Independence Measure), which assesses dysfunction in daily-living
activities; various electrophysiological tests designed to assess neuronal
conduction; magnetic resonance imaging (MRI); and urodynamic testing for
bladder function.
....................................

TRANSPLANTATION PROCEDURES:

1) Embryonic/Fetal Cells: In 1996, the Russian Health Ministry authorized
Bryukhovetskiy to carry out limited clinical trials in SCI. In these early
trials, stem cells, neurons, and glia obtained from a various tissues,
including 12-week-old human fetuses, were transplanted into the spinal
cord/fluid of 17 patients with SCI. Their ages ranged from 16-52 (average
30) years, and the time interval between injury and transplantation ranged
from 1-20 (average 5) years. Six, ten, and one had cervical, thoracic, and
lumbar injuries respectively. In addition to cell transplantation, all had a
variety of other procedures performed depending upon their unique injuries.

Before treatment, 14 subjects were ASIA grade A and three were grade B.
After transplantation (0.5 - 3-year follow-up period), four were grade A,
five grade B, and seven grade C.  Fifteen had some sensory improvement,
seven had motor improvement, and 12 had improved bladder function.

2) SpheroGel & Autologous Cells: Bryukhovetskiy's team has implanted
SpheroGel (a biodegradable polymer matrix) with embedded cells in six
patients who required reconstructive surgeries. In three, hematopoietic stem
cells were embedded, and, in the three others, olfactory cells. At follow-up
(3-8 months), two grade-A patients had improved to grade C, and one had
advanced to grade B. In one patient (grade B initially), there was no
improvement.

3) Intrathecal Stem-Cell Transfusion: The intrathecal transfusion of
autologous hematopoietic stem cells is the procedure most currently used. In
this relatively straight-forward procedure involving no surgery, the
patient's stem cells are collected without anesthesia and stored with
viability until they are transfused back into the patient.

To stimulate hematopoietic stem-cell production and, in turn, cell
accumulation in the blood, patients typically received eight subcutaneous
injections over four days of granulocytic colony-stimulating factor, a drug
also called NeupogenR or Filgrastim. On day five, the patient is hooked up
to a blood separator. Over 3-4 hours, blood is drawn from a vein; processed
by the separator, which isolates the stems cells; and returned through
another vein.

The collected stem cells are concentrated by centrifugation and slowly
frozen in liquid nitrogen (-170o centigrade) in the presence of dimethyl
sulfoxide (DMSO), a cryopreservative that allows cells to be frozen with
minimal damage. Care is taken to check for infections so that they will not
be later introduced behind the protective blood-brain barrier during
transfusion.

At the time of transfusion, the stem-cell suspension is thawed and about
5.3-million cells injected intrathecally into the subarachnoid space (i.e.,
into the spinal fluid) through a L3-L4 lumbar puncture using a local
anesthetic. The procedure, which I observed, is quick and straightforward.
The patient can repeat the transfusion in two months. Bryukhovetskiy
believes multiple transfusions enhance functional recovery.

In contrast to hematopoietic stem cells, positive results have been limited
with the intrathecal transfusion of olfactory cells, previously isolated and
cultured from the patient's nasal tissue.

Although Bryukhovetskiy's team has collected stem cells from about 120
patients, for a variety of reasons, including the presence of latent
infections, only about 60 have had cells reintroduced. Of these 60, 18 have
had the recommended multiple transfusions. In turn, 61% of the 18 showed
some functional recovery, in some cases dramatic.

Because most patients' transfusions were relatively recent, it is too early
to assess long-term benefit.  Early improvements are unlikely caused by
comparatively slow neuronal regeneration processes and are probably
triggered by altering the injury site's environment through the secretion of
growth factors and other molecules.

For more scientifically inclined readers, Bryukhovetskiy hypothesizes that
the stem-cells' regenerative effects are mediated through an important
growth factor called ciliary neurotrophic factor (CNTF) and its interaction
with a key transmembrane receptor called gp130. This interaction, in turn,
influences cell differentiation.
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PHYSICAL REHABILITATION:
Like others who are developing function-restoring therapies, Bryukhovetskiy
strongly believes that improvement after treatment depends upon the
patient's commitment to aggressive physical rehabilitation designed to
maximize restored function. Basically, if muscles have been disconnected
from brain control for many years, it's going to take some real work to
build up nascent connections. As such, his clinic emphasizes diverse
rehabilitation modalities, ranging from aggressive exercises to passive
massage and acupuncture therapy.
....................................

PATIENTS:
I had the opportunity to interact with a number of NeuroVita patients.
Because their treatments have been relatively recent, accrued improvements
have been generally modest.

Vladimir, a 40-year old Russian living in Spain, sustained a thoracic T6
complete injury from a 2001 car accident, and started a series of stem-cell
transfusions late last year. He believes that these recent transfusions,
combined with extensive physical therapy, has resulted in additional leg
movement, including the ability to walk in a swimming pool.

An articulate 19-year-old Russian living in Bulgaria, Dmitri sustained a
cervical C5-6 injury in a 2000 skiing accident. He has had three
transfusions since the beginning of 2005 and has noted new sensation and
sweating. He had some slight headaches soon after the transfusions.

From Dagestan, Baziat, 21, sustained a T9-11 injury when she was 19. After
four transfusions, she has regained additional leg and hip function.

Alexey, 32, traveled in from the distant Kamchatka Peninsula on Russia's far
eastern Pacific side, much closer to Alaska than Moscow. He shared with me
the challenges of living with a severe physical disability in a remote,
almost frontier-like area of Russia. Sustaining a T-8 gunshot injury 11
years ago, he received his first transfusion last year and was scheduled to
receive his third during my visit. He has acquired more bladder and bowel
function and has increased leg strength and tension.  

Olga, 17, sustained a T8-9 injury seven years ago from an accident. Last
year, cell-containing SpheroGel was implanted in the 4-cm gap in her spinal
cord. Since then, she also has had six intrathecal transfusions. Olga
indicated some increased lower-back strength and improved "inner sensation."


A year after injury, another Olga had the 5-cm gap at her T12-injury site
filled with SpheroGel embedded with regenerative cells. About a year after
surgery, she suddenly started gaining some dramatic improvement, which she
demonstrated to me in NeuroVita's rehabilitation facility.

These are just the patients that I met. For those interested in further
patient feedback, the clinic has developed a DVD with English subtitles that
includes interviews with other NeuroVita patients.
....................................

CONCLUSION:
Although by itself probably not an end-all SCI panacea, this Russian
stem-cell therapy is an exceedingly important piece of the puzzle that
brings us ever closer to our overall goal of restored function after injury.
Hopefully, American scientists can open-mindedly establish collaborations
with Bryukhovetskiy so that Americans with SCI can more readily benefit.

Although Bryukhovetskiy's work is of paramount importance, when discussing
hot scientific topics like stem-cell therapy, it is easy to lose track of
the fact that it is the patient who ultimately counts, not the science. In
science's cold objective eye, the patient becomes a research subject
characterized by an impairment-scale, etc, and whose subjective opinions are
often left in the dust of our quest for scientific purity. 

I was grateful for the opportunity to interact with NeuroVita's patients,
appreciating their willingness to share with me not only their pain and
frustration, but their hope, optimism, and belief in the future. As a
somewhat jaded disability-research veteran, their spirit fueled mine.

In this clinic and others throughout the world I have visited, the face of
SCI seems so similar. Often with the support of devoted parents, youthful
patients with great resolve, motivation, and old-soul wisdom that belies
their youth pursue their dreams of recovery unencumbered with the limited
expectations of the past.

In spite of unique injuries, there seems to be a collective "soul of SCI" in
these patients that transcends culture and country. Although the efforts of
innovative scientists, such as Bryukhovetskiy, are invaluable, the patients
are the true pioneers. They each send forth a ripple of hope that is
converging into a powerful current which will inevitably wash away SCI's
imprisoning walls.

Contact Information: NeuroVita Clinic, Kashirskoye Avenue 23A, Moscow,
Russia; info@neurovita.ru or www.NeuroVita.ru.

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