An Interview with Wise Young, MD
Wise Young, MD, PhD, director
of the Neuroscience Center and
the Spinal Cord Injury Project at
Rutgers University, is an
internationally-renowned SCI
research scientist. Among his
accomplishments, Young
participated in pioneering research
that led to the development of
high-dose methylprednisolone as a
treatment for acute SCI. This drug
improves neurologic recovery by
an average of about 20% when
given to people within several
hours after injury, and its use is
now standard practice in SCI
trauma care.
We recently interviewed Young
about the progress of SCI
research today. His responses will
be published in two installments;
Part 2 will appear in the next issue.
Part 1
Q: Over the last year or
two there have been
promising breakthroughs
in nerve cell regeneration
research. Which avenues
of research do you think
are most likely to lead to a
cure for SCI?
Wise Young, MD, in his
laboratory at Rutgers University
A: Much research indicates that spinal axons can regrow but the spinal
cord contains substances that prevent
growth. Several therapeutic approaches have shown promise in animal
studies.
1.Blocking growth inhibitors in the spinal cord. Martin Schwab and
his colleagues at the University of Zurich
discovered an antibody called IN-1, which appears to block the
growth-inhibiting substances in the spinal
cord. These inhibitors appear to be concentrated in myelin, a
material that wraps around spinal axons and
improves conduction. Myelin is white and consequently areas of the
spinal cord that contain myelin are called
white matter (WM). Implantation of cells that produce IN-1 in rats
promoted spinal cord regeneration. Much
effort has gone be used in humans and IN-1 may well be one of the
first therapies to go into clinical trial,
perhaps in the next two years.
2.Diverting regenerating axons into gray matter. Heinreich Cheng,
Lars Olson, and colleagues in Sweden
showed that it is possible to get some regeneration to occur in
rats by using peripheral nerve bridges to direct
the growth of spinal axons into gray matter (GM), a part of the
spinal cord that is more conducive to
regeneration. Cheng and Olson's work lends credence to Schwab's
finding that WM inhibits growth,
demonstrates that axons can grow long distances in GM, and provides
a potential surgical approach to
reconnecting transected spinal cords.
3.Building cellular bridges. Several studies suggest that it is
possible to use other cells and materials to bridge
the gap. Doug Anderson and Paul Reier at the University of Florida
at Gainesville transplanted fetal spinal
cords to the injury site in humans, based on the notion that fetal
cells might support growth. These studies
showed that fetal cells will survive at the injury site and will
support some growth.
Two patients received fetal cell transplants last year in Florida
and dozens have received such transplants in
Sweden and Russia. Results from this procedure have been
inconclusive so far. Mary Bunge and colleagues at
the Miami Project have been using artificial bridges and Schwann
cells. More recently, two groups (Geoffrey
Raisman of the University of London and Mary Bunge) reported that a
special kind of cell from the nose,
called olfactory ensheathing glial cells, will support the
regeneration of axons in the spinal cord.
4.Enhancing natural repair mechanisms. Last year the Multicenter
Animal Spinal Cord Injury Study, a
consortium of SCI laboratories that are working together to develop
and test therapies, discovered that injured
rat spinal cords show limited regeneration without any external
therapy. This has led to intense studies of
natural factors that may enhance regeneration. Last month Michal
Schwartz and her colleagues at the
Weitzmann Institute reported that transplantation of activated
macrophages into transected rat spinal cords
apparently promotes regeneration and some functional recovery in
rats. In our laboratory at Rutgers, we have
found that injured spinal cords express a cellular adhesion
molecule called L1, and administration of additional
L1 to the spinal cord can enhance regeneration and functional
recovery in the injured cord.
Q: Can you tell us about your current research?
A: We have devoted much of our effort to developing standardized tools
for collaborative research in SCI, and we
have validated outcome measures that many laboratories have adopted so
that everybody knows what is meant when
a rat is said to walk, when there is less tissue damage, or when there
is regeneration. Using these tools, the field can
now systematically develop and test therapies efficiently.
Most of our laboratory work is focused on four treatments: L1, M1, MP,
and pregnenolone. L1 is a cellular adhesion
molecule associated with increased growth and recovery in rats (see
above). M1, an antibody discovered by Moses
Rodriguez at the Mayo Clinic, is in the same family of antibodies as
IN-1 (see above) and has been shown to
promote remyelination in various animal models. MP is a corticosteroid
that not only protects spinal cords against
progressive tissue damage but may also promote regeneration.
Pregnenolone, a steroid molecule produced by the
central nervous system, makes spinal cords tolerant of prolonged oxygen
deprivation, and others have reported that it
improves repair and regeneration.
Two other projects in the laboratory are also quite exciting. First, we
are systematically studying injured spinal cords
to find out which molecules expressed after injury can signal axonal
growth. If we can identify these signals, it will be
possible to apply them to the chronic cord to kickstart growth again.
Second, we have been transplanting fetal oligodendroglial cells into the
spinal cord. About a third of those with SCI
have enough surviving axons but these axons have been demyelinated and
cannot efficiently conduct signals. Last
year, we showed that transplanted oligodendroglial cells will
remyelinate axons in rats with SCI.
The Spinal Cord Injury Project can be reached at Neuroscience Center,
Rutgers University, 604 Allison Rd.,
D413, Piscataway, NJ 08854-8082 (732-445-6573,445-2061;
SCIProj(AT)biology.rutgers.edu).
Next Issue: In Part 2 of this interview, Wise Young proposes a timetable
for a cure for SCI and cautions readers
about unproved therapies.
=A9 1998 Northwest Regional Spinal Cord Injury
System