A USC-invented vaccine for multiple sclerosis New Trial
Posted: Tue Nov 30, 2004 8:50 am
Early days, but an interesting approach.
A USC-invented vaccine for multiple sclerosis (MS) is about to enter
Phase II clinical trials
http://www.usc.edu/hsc/info/pr/1vol5/526/ms.html
A USC-invented vaccine for multiple sclerosis (MS) is about to enter
Phase II clinical trials, backed by a combined $3.5 million in
funding-including a $1.1 million award from the National Multiple
Sclerosis Society that is one of its largest in recent memory, as well
as $2.4 million from the National Institute of Neurological Disorders
and Stroke (NINDS).
While the vaccine is unlikely to rid patients of their current MS
symptoms, said Keck School of Medicine professor Leslie Weiner, chair of
the Department of Neurology and co-inventor of the vaccine, results from
the Phase I study on four patients indicate that it may well be able to
halt the disease in its tracks.
Weiner and former faculty member Jorge Correale, now head of neurology
at FLENI, a foundation and neurologic institute in Buenos Aires,
Argentina, that is involved in the fight against neurological diseases,
came up with the idea for the vaccine together some 6 years ago. A
patent is currently pending, and the Phase II trial has an
Investigational New Drug number, which means the Food and Drug
Administration has looked at and approved the trial.
Multiple sclerosis is a chronic and oftentimes progressive and
debilitating condition that affects some 250,000 to 350,000 Americans.
According to the NINDS, physicians diagnose 200 new cases of MS each
week. It seems to be an autoimmune condition, a disease in which certain
white blood cells turn on the body that produces them.
The best current hypotheses say that MS is caused by the body's T-cells
attacking the myelin sheaths that serve as the insulation for the
conduction of electricity and coat and protect the long, delicate axons
of the brain's neurons.
"This vaccine allows the patient's immune system to take control of the
disease," said Weiner. "At the end of two years of vaccinations, we hope
they will never need treatment again."
Weiner and his USC colleagues are currently recruiting patients for the
three-year-long trial, in which 40 people with MS will receive the
active vaccine and another 40 will receive a placebo.
Patients are eligible for the trial if they have what is known as
secondary progressive multiple sclerosis-they had periods of both
remission and relapse for some time, and now are experiencing a
significant progression of the disease (though they may still be
symptom-free at times). They also must be between 12 and 65 years of age
and be able to walk at least 50 feet, though use of a cane or walker is
acceptable.
"It's a very hard task to take sick patients and ask 40 to get a placebo
and go off everything else," Weiner admitted. "But we think it's worth
it because of the potential benefits of this vaccine." In addition, he
noted, most of the patients in this trial will likely be treatment
failures on the limited number of treatments available for MS, and so
abandoning those treatments should not be detrimental.
Patients accepted into the trial will have a baseline MRI to measure the
MS lesions in their brains, and then will undergo a process called
leukapheresis, in which their white blood cells are removed from their
body. (Since the body is continually producing white cells-and in fact
will replace the ones removed within 24 hours-this does not have any
long-term effect.)
To create an individualized vaccine, the research team will then expose
those cells to myelin from a cow brain, which should prompt the
characteristic MS response from the misguided, autoimmune T-cells. (The
cow brains have been examined for any evidence of the so-called mad cow
disease-bovine spongiform encephalopathy-in collaboration with Nobel
laureate Stanley Prusiner of the University of California, San
Francisco, and have been approved for use in the preparation of these
vaccines.)
Those T-cells are then exposed to 12,000 rads of radiation, killing them
and at the same time altering them subtly, so that when they are
reintroduced into the body, they will be seen as foreign. That
reintroduction-or vaccination-should prompt the immune system to create
antibodies and reactive T-cells against the MS-causing T-cells. "We
vaccinate them against their own bad T-cells, their own bad
lymphocytes," Weiner explained. "After that, they should be immune to
the cells they produce that attack their white matter at any time in the
future, because they have a memory for the bad T-cells."
How will this help the patient? Simply put, if the body destroys the
autoimmune T-cells before they can get to the myelin, this
sometimes-devastating disease should be stalled in its tracks. "We don't
anticipate that it will get anyone out of a wheelchair," said Weiner.
"But we think we can prevent the progression of the disease. We will
have made their immune systems 'normal' again, leaving the future repair
of their nervous system an easier task."
Vaccines will be created for both the vaccine and placebo groups. If the
trial shows that the vaccine is useful, it may be possible to then
vaccinate the placebo group as well.
Weiner is optimistic about the vaccine's chances.
"We're giving them weapons to kill their self-immune responses, which
you and I can do on our own. In the vaccinated patients, the good
T-cells are interacting with the bad T-cells and killing them."
The patients will receive vaccinations every month for three months, and
then every three months for two years at the General Clinical Research
Center, an NIH-supported facility at LAC+USC Medical Center. The third
year of the study will simply be follow-up, to see whether the effects
of the vaccination persist over time.
The vaccine will be deemed successful if it can halt the progression of
existing lesions and the appearance of new MS lesions, as measured by
MRI. Weiner and his colleagues will also look at any changes in
neurologic function and will be monitoring any and all side effects of
the vaccine.
From a scientific point of view, Weiner noted, the study will most
likely put the lid on the debate over whether myelin is indeed the
immune system target in MS; scientists have long assumed that to be the
case, but it has yet to be definitively proven.
An even more interesting question that the trial will address, he noted,
is just how the immune system is able to get quite so out of control,
spewing out the literally self-destructive T-cells at an ever-increasing
rate.
"The implications of this trial are really quite interesting," said
Weiner. "We've made a case that this is worth doing scientifically.
Overall, I think this trial is very exciting for USC, especially since
the vaccine was invented, developed and manufactured here."
by Lori Oliwenstein.
Regards to all
A USC-invented vaccine for multiple sclerosis (MS) is about to enter
Phase II clinical trials
http://www.usc.edu/hsc/info/pr/1vol5/526/ms.html
A USC-invented vaccine for multiple sclerosis (MS) is about to enter
Phase II clinical trials, backed by a combined $3.5 million in
funding-including a $1.1 million award from the National Multiple
Sclerosis Society that is one of its largest in recent memory, as well
as $2.4 million from the National Institute of Neurological Disorders
and Stroke (NINDS).
While the vaccine is unlikely to rid patients of their current MS
symptoms, said Keck School of Medicine professor Leslie Weiner, chair of
the Department of Neurology and co-inventor of the vaccine, results from
the Phase I study on four patients indicate that it may well be able to
halt the disease in its tracks.
Weiner and former faculty member Jorge Correale, now head of neurology
at FLENI, a foundation and neurologic institute in Buenos Aires,
Argentina, that is involved in the fight against neurological diseases,
came up with the idea for the vaccine together some 6 years ago. A
patent is currently pending, and the Phase II trial has an
Investigational New Drug number, which means the Food and Drug
Administration has looked at and approved the trial.
Multiple sclerosis is a chronic and oftentimes progressive and
debilitating condition that affects some 250,000 to 350,000 Americans.
According to the NINDS, physicians diagnose 200 new cases of MS each
week. It seems to be an autoimmune condition, a disease in which certain
white blood cells turn on the body that produces them.
The best current hypotheses say that MS is caused by the body's T-cells
attacking the myelin sheaths that serve as the insulation for the
conduction of electricity and coat and protect the long, delicate axons
of the brain's neurons.
"This vaccine allows the patient's immune system to take control of the
disease," said Weiner. "At the end of two years of vaccinations, we hope
they will never need treatment again."
Weiner and his USC colleagues are currently recruiting patients for the
three-year-long trial, in which 40 people with MS will receive the
active vaccine and another 40 will receive a placebo.
Patients are eligible for the trial if they have what is known as
secondary progressive multiple sclerosis-they had periods of both
remission and relapse for some time, and now are experiencing a
significant progression of the disease (though they may still be
symptom-free at times). They also must be between 12 and 65 years of age
and be able to walk at least 50 feet, though use of a cane or walker is
acceptable.
"It's a very hard task to take sick patients and ask 40 to get a placebo
and go off everything else," Weiner admitted. "But we think it's worth
it because of the potential benefits of this vaccine." In addition, he
noted, most of the patients in this trial will likely be treatment
failures on the limited number of treatments available for MS, and so
abandoning those treatments should not be detrimental.
Patients accepted into the trial will have a baseline MRI to measure the
MS lesions in their brains, and then will undergo a process called
leukapheresis, in which their white blood cells are removed from their
body. (Since the body is continually producing white cells-and in fact
will replace the ones removed within 24 hours-this does not have any
long-term effect.)
To create an individualized vaccine, the research team will then expose
those cells to myelin from a cow brain, which should prompt the
characteristic MS response from the misguided, autoimmune T-cells. (The
cow brains have been examined for any evidence of the so-called mad cow
disease-bovine spongiform encephalopathy-in collaboration with Nobel
laureate Stanley Prusiner of the University of California, San
Francisco, and have been approved for use in the preparation of these
vaccines.)
Those T-cells are then exposed to 12,000 rads of radiation, killing them
and at the same time altering them subtly, so that when they are
reintroduced into the body, they will be seen as foreign. That
reintroduction-or vaccination-should prompt the immune system to create
antibodies and reactive T-cells against the MS-causing T-cells. "We
vaccinate them against their own bad T-cells, their own bad
lymphocytes," Weiner explained. "After that, they should be immune to
the cells they produce that attack their white matter at any time in the
future, because they have a memory for the bad T-cells."
How will this help the patient? Simply put, if the body destroys the
autoimmune T-cells before they can get to the myelin, this
sometimes-devastating disease should be stalled in its tracks. "We don't
anticipate that it will get anyone out of a wheelchair," said Weiner.
"But we think we can prevent the progression of the disease. We will
have made their immune systems 'normal' again, leaving the future repair
of their nervous system an easier task."
Vaccines will be created for both the vaccine and placebo groups. If the
trial shows that the vaccine is useful, it may be possible to then
vaccinate the placebo group as well.
Weiner is optimistic about the vaccine's chances.
"We're giving them weapons to kill their self-immune responses, which
you and I can do on our own. In the vaccinated patients, the good
T-cells are interacting with the bad T-cells and killing them."
The patients will receive vaccinations every month for three months, and
then every three months for two years at the General Clinical Research
Center, an NIH-supported facility at LAC+USC Medical Center. The third
year of the study will simply be follow-up, to see whether the effects
of the vaccination persist over time.
The vaccine will be deemed successful if it can halt the progression of
existing lesions and the appearance of new MS lesions, as measured by
MRI. Weiner and his colleagues will also look at any changes in
neurologic function and will be monitoring any and all side effects of
the vaccine.
From a scientific point of view, Weiner noted, the study will most
likely put the lid on the debate over whether myelin is indeed the
immune system target in MS; scientists have long assumed that to be the
case, but it has yet to be definitively proven.
An even more interesting question that the trial will address, he noted,
is just how the immune system is able to get quite so out of control,
spewing out the literally self-destructive T-cells at an ever-increasing
rate.
"The implications of this trial are really quite interesting," said
Weiner. "We've made a case that this is worth doing scientifically.
Overall, I think this trial is very exciting for USC, especially since
the vaccine was invented, developed and manufactured here."
by Lori Oliwenstein.
Regards to all
hi don't want to put a downer on this but this information was printed in 1999 surley we would have heard more about it by now?????