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http://www.nanowerk.com/news/newsid=15042.php
Drug delivery breakthrough targets organelles
(Nanowerk News) A team of scientists led by Dr Simon Richardson at the
University of Greenwich has got a step closer to one of the holy grails of
drug delivery.
The goal – to find a vehicle that can carry drugs not just to a specific
cell but a specific organ (organelle) inside the cell, and accurately
measure how it behaves when it gets there – has proved elusive despite two
decades of research, according to the Journal of Controlled Release ("Intracellular
fate of bioresponsive poly(amidoamine)s in vitro and in vivo").
Now the journal has given the new research front page billing, saying in an
editorial that Richardson and colleagues provide direct evidence, for the
first time, that nanomedicines can be delivered to select organelles and
manipulated to carry beneficial agents like genes.
Dr Richardson says: “Drug delivery is important for everyone because it has
the potential to deliver new treatments for diseases which are currently
incurable; and to deliver existing drugs more effectively.”
“We are trying to smuggle healthy genes inside cells. Genes are large
molecules which have up till now proved too big to get in without serious
risk to the patient. Our research is at the cutting edge of efforts to turn
gene therapy, and new molecular medicines, from risky and sci-fiesque to
safe and routine.”
As well as proving that material like genes can be delivered to the target
organelle, the team was also able to show how the delivery vehicle behaves
once inside.
Editor of the Journal of Controlled Release, Professor Kinam Park, said the
study was “distinguished from others by its thoroughness and unequivocal
data” and concludes: “…the approach used by Richardson’s team can be useful
in developing more efficient delivery vehicles for drug targeting in
general.”
Source: University of Greenwich
http://gazette.jhu.edu/2010/02/22/nih-grant-funds-study-on-stem-cells-from-als-patients/
NIH grant funds study on stem cells from ALS patients
Lead researcher Jeffrey Rothstein,
right, and Nicholas Maragakis will provide the cells generated
in their program to other researchers nationwide. Photo: Will
Kirk/Homewoodphoto.jhu.edu
A two-year $3.7 million stimulus grant from the National
Institutes of Health will allow Johns Hopkins neurologist and lead
researcher Jeffrey Rothstein to expand on his long-standing research
into the nerve- and muscle-wasting disease amyotrophic lateral
sclerosis, or ALS.
Using stem cells developed in a laboratory from skin cell samples
taken from 20 ALS patients and five control subjects, Rothstein and
his colleagues will study the biology and chemistry involved in the
development and progression of the disease and will test drugs to
intervene in the process. When the two-year program is completed,
the cells generated will be available nationwide to other
researchers.
“We believe that the ability to work with the two types of cells
most relevant for ALS, developed directly from ALS patients, will
give us a tremendous boost toward understanding more about this
disease,” said Rothstein, a professor of neurology and neuroscience
and director of the Robert Packard Center for ALS Research at Johns
Hopkins. “Importantly, this will serve as a scientifically rich
national resource for human ALS cell lines.”
ALS, also known as Lou Gehrig’s disease, is characterized by a
gradual loss of muscle strength and coordination. The disease is
fatal, with only about 20 percent of patients living more than five
years beyond diagnosis.
The funding for the Johns Hopkins work comes from an NIH Grand
Opportunities grant, part of the American Recovery and Reinvestment
Act of 2009. According to the NIH, the grants in this program
“provide investigators and institutions with the opportunity to
engage in new avenues of research with a high likelihood of
significant impact on growth and investment in biomedical or
behavioral research and development, public health and health care
delivery.”
“This program will provide the first national tissue resource of
real human ALS cells that could be used in projects ranging from
understanding the disease to the discovery of new effective
therapies,” Rothstein said. “By having a centralized, highly
characterized tissue resource, we can help catalyze research on this
disease nationally, and advance therapeutics.”
The award will be shared with three other laboratories, one at
Harvard University and two at Columbia University. The project will
create at least three new jobs in the labs at Johns Hopkins, as well
as multiple jobs at the collaborating sites, Rothstein said.
The Johns Hopkins team will collaborate with San Francisco–based
biopharmaceutical company iPierian, which specializes in working
with the novel stem cells to be used in this project. The stem cells,
known as induced pluripotent stem, or iPS cells, can develop into
cells that populate many organs but are derived from non-stem cells.
The scientists plan to grow iPS cells from ALS patients’ skin, then
steer them to develop into motor neurons and astrocytes, the two
types of nerve cells that are affected in ALS.
Previous studies of ALS have been hindered by the fact that
researchers can’t use patients’ actual neurons in studies. By
generating iPS cells, Rothstein and his colleagues hope to open up
new avenues for research and discovery.
Rothstein will be working with Johns Hopkins School of Medicine
colleagues Nicholas Maragakis, an associate professor of neurology,
and Dwight Bergles, an associate professor of neuroscience, who will
be analyzing the iPS cells for functional properties so the team
will know when they have succeeded in making an astrocyte before
providing the cells as a national resource.
Rothstein’s investigation is among the more than 340 stimulus-funded
research grants and supplements totaling more than $160.3 million
that Johns Hopkins has garnered since Congress passed the American
Recovery and Reinvestment Act of 2009 (informally known by the
acronym ARRA), bestowing the National Institutes of Health and the
National Science Foundation with $12.4 billion in extra money to
underwrite research grants by September 2010. The stimulus package—which
provided $550 billion in new spending, including the above grants—is
part of the federal government’s attempt to bring back a stumbling
economy by distributing dollars for transportation projects,
infrastructure building, the development of new energy sources and
job creation, and financing research that will benefit humankind.
Johns Hopkins scientists have submitted about 1,300 proposals for
stimulus-funded investigations, ranging from strategies to help
recovering addicts stay sober and the role that certain proteins
play in the development of muscular dystrophy to mouse studies
seeking to understand how men and women differ in their response to
the influenza virus.
To date, 112 jobs have been created at Johns Hopkins through ARRA
funding.
Read more:
http://gazette.jhu.edu/2010/02/22/nih-grant-funds-study-on-stem-cells-from-als-patients/#ixzz0gSZxMNLk
NIH grant funds study on stem cells from ALS patients
Lead researcher Jeffrey Rothstein,
right, and Nicholas Maragakis will provide the cells generated
in their program to other researchers nationwide. Photo: Will
Kirk/Homewoodphoto.jhu.edu
A two-year $3.7 million stimulus grant from the National
Institutes of Health will allow Johns Hopkins neurologist and lead
researcher Jeffrey Rothstein to expand on his long-standing research
into the nerve- and muscle-wasting disease amyotrophic lateral
sclerosis, or ALS.
Using stem cells developed in a laboratory from skin cell samples
taken from 20 ALS patients and five control subjects, Rothstein and
his colleagues will study the biology and chemistry involved in the
development and progression of the disease and will test drugs to
intervene in the process. When the two-year program is completed,
the cells generated will be available nationwide to other
researchers.
“We believe that the ability to work with the two types of cells
most relevant for ALS, developed directly from ALS patients, will
give us a tremendous boost toward understanding more about this
disease,” said Rothstein, a professor of neurology and neuroscience
and director of the Robert Packard Center for ALS Research at Johns
Hopkins. “Importantly, this will serve as a scientifically rich
national resource for human ALS cell lines.”
ALS, also known as Lou Gehrig’s disease, is characterized by a
gradual loss of muscle strength and coordination. The disease is
fatal, with only about 20 percent of patients living more than five
years beyond diagnosis.
The funding for the Johns Hopkins work comes from an NIH Grand
Opportunities grant, part of the American Recovery and Reinvestment
Act of 2009. According to the NIH, the grants in this program
“provide investigators and institutions with the opportunity to
engage in new avenues of research with a high likelihood of
significant impact on growth and investment in biomedical or
behavioral research and development, public health and health care
delivery.”
“This program will provide the first national tissue resource of
real human ALS cells that could be used in projects ranging from
understanding the disease to the discovery of new effective
therapies,” Rothstein said. “By having a centralized, highly
characterized tissue resource, we can help catalyze research on this
disease nationally, and advance therapeutics.”
The award will be shared with three other laboratories, one at
Harvard University and two at Columbia University. The project will
create at least three new jobs in the labs at Johns Hopkins, as well
as multiple jobs at the collaborating sites, Rothstein said.
The Johns Hopkins team will collaborate with San Francisco–based
biopharmaceutical company iPierian, which specializes in working
with the novel stem cells to be used in this project. The stem cells,
known as induced pluripotent stem, or iPS cells, can develop into
cells that populate many organs but are derived from non-stem cells.
The scientists plan to grow iPS cells from ALS patients’ skin, then
steer them to develop into motor neurons and astrocytes, the two
types of nerve cells that are affected in ALS.
Previous studies of ALS have been hindered by the fact that
researchers can’t use patients’ actual neurons in studies. By
generating iPS cells, Rothstein and his colleagues hope to open up
new avenues for research and discovery.
Rothstein will be working with Johns Hopkins School of Medicine
colleagues Nicholas Maragakis, an associate professor of neurology,
and Dwight Bergles, an associate professor of neuroscience, who will
be analyzing the iPS cells for functional properties so the team
will know when they have succeeded in making an astrocyte before
providing the cells as a national resource.
Rothstein’s investigation is among the more than 340 stimulus-funded
research grants and supplements totaling more than $160.3 million
that Johns Hopkins has garnered since Congress passed the American
Recovery and Reinvestment Act of 2009 (informally known by the
acronym ARRA), bestowing the National Institutes of Health and the
National Science Foundation with $12.4 billion in extra money to
underwrite research grants by September 2010. The stimulus package—which
provided $550 billion in new spending, including the above grants—is
part of the federal government’s attempt to bring back a stumbling
economy by distributing dollars for transportation projects,
infrastructure building, the development of new energy sources and
job creation, and financing research that will benefit humankind.
Johns Hopkins scientists have submitted about 1,300 proposals for
stimulus-funded investigations, ranging from strategies to help
recovering addicts stay sober and the role that certain proteins
play in the development of muscular dystrophy to mouse studies
seeking to understand how men and women differ in their response to
the influenza virus.
To date, 112 jobs have been created at Johns Hopkins through ARRA
funding.
Read more:
http://gazette.jhu.edu/2010/02/22/nih-grant-funds-study-on-stem-cells-from-als-patients/#ixzz0gSZxMNLk
NIH grant funds study on stem cells from ALS patients
Lead researcher Jeffrey Rothstein,
right, and Nicholas Maragakis will provide the cells generated
in their program to other researchers nationwide. Photo: Will
Kirk/Homewoodphoto.jhu.edu
A two-year $3.7 million stimulus grant from the National
Institutes of Health will allow Johns Hopkins neurologist and lead
researcher Jeffrey Rothstein to expand on his long-standing research
into the nerve- and muscle-wasting disease amyotrophic lateral
sclerosis, or ALS.
Using stem cells developed in a laboratory from skin cell samples
taken from 20 ALS patients and five control subjects, Rothstein and
his colleagues will study the biology and chemistry involved in the
development and progression of the disease and will test drugs to
intervene in the process. When the two-year program is completed,
the cells generated will be available nationwide to other
researchers.
“We believe that the ability to work with the two types of cells
most relevant for ALS, developed directly from ALS patients, will
give us a tremendous boost toward understanding more about this
disease,” said Rothstein, a professor of neurology and neuroscience
and director of the Robert Packard Center for ALS Research at Johns
Hopkins. “Importantly, this will serve as a scientifically rich
national resource for human ALS cell lines.”
ALS, also known as Lou Gehrig’s disease, is characterized by a
gradual loss of muscle strength and coordination. The disease is
fatal, with only about 20 percent of patients living more than five
years beyond diagnosis.
The funding for the Johns Hopkins work comes from an NIH Grand
Opportunities grant, part of the American Recovery and Reinvestment
Act of 2009. According to the NIH, the grants in this program
“provide investigators and institutions with the opportunity to
engage in new avenues of research with a high likelihood of
significant impact on growth and investment in biomedical or
behavioral research and development, public health and health care
delivery.”
“This program will provide the first national tissue resource of
real human ALS cells that could be used in projects ranging from
understanding the disease to the discovery of new effective
therapies,” Rothstein said. “By having a centralized, highly
characterized tissue resource, we can help catalyze research on this
disease nationally, and advance therapeutics.”
The award will be shared with three other laboratories, one at
Harvard University and two at Columbia University. The project will
create at least three new jobs in the labs at Johns Hopkins, as well
as multiple jobs at the collaborating sites, Rothstein said.
The Johns Hopkins team will collaborate with San Francisco–based
biopharmaceutical company iPierian, which specializes in working
with the novel stem cells to be used in this project. The stem cells,
known as induced pluripotent stem, or iPS cells, can develop into
cells that populate many organs but are derived from non-stem cells.
The scientists plan to grow iPS cells from ALS patients’ skin, then
steer them to develop into motor neurons and astrocytes, the two
types of nerve cells that are affected in ALS.
Previous studies of ALS have been hindered by the fact that
researchers can’t use patients’ actual neurons in studies. By
generating iPS cells, Rothstein and his colleagues hope to open up
new avenues for research and discovery.
Rothstein will be working with Johns Hopkins School of Medicine
colleagues Nicholas Maragakis, an associate professor of neurology,
and Dwight Bergles, an associate professor of neuroscience, who will
be analyzing the iPS cells for functional properties so the team
will know when they have succeeded in making an astrocyte before
providing the cells as a national resource.
Rothstein’s investigation is among the more than 340 stimulus-funded
research grants and supplements totaling more than $160.3 million
that Johns Hopkins has garnered since Congress passed the American
Recovery and Reinvestment Act of 2009 (informally known by the
acronym ARRA), bestowing the National Institutes of Health and the
National Science Foundation with $12.4 billion in extra money to
underwrite research grants by September 2010. The stimulus package—which
provided $550 billion in new spending, including the above grants—is
part of the federal government’s attempt to bring back a stumbling
economy by distributing dollars for transportation projects,
infrastructure building, the development of new energy sources and
job creation, and financing research that will benefit humankind.
Johns Hopkins scientists have submitted about 1,300 proposals for
stimulus-funded investigations, ranging from strategies to help
recovering addicts stay sober and the role that certain proteins
play in the development of muscular dystrophy to mouse studies
seeking to understand how men and women differ in their response to
the influenza virus.
To date, 112 jobs have been created at Johns Hopkins through ARRA
funding.
Read more:
http://gazette.jhu.edu/2010/02/22/nih-grant-funds-study-on-stem-cells-from-als-patients/#ixzz0gSZxMNLk
study on stem cells from ALS patients
Lead researcher Jeffrey Rothstein,
right, and Nicholas Maragakis will provide the cells generated
in their program to other researchers nationwide. Photo: Will
Kirk/Homewoodphoto.jhu.edu
A two-year $3.7 million stimulus grant from the National
Institutes of Health will allow Johns Hopkins neurologist and lead
researcher Jeffrey Rothstein to expand on his long-standing research
into the nerve- and muscle-wasting disease amyotrophic lateral
sclerosis, or ALS.
Using stem cells developed in a laboratory from skin cell samples
taken from 20 ALS patients and five control subjects, Rothstein and
his colleagues will study the biology and chemistry involved in the
development and progression of the disease and will test drugs to
intervene in the process. When the two-year program is completed,
the cells generated will be available nationwide to other
researchers.
“We believe that the ability to work with the two types of cells
most relevant for ALS, developed directly from ALS patients, will
give us a tremendous boost toward understanding more about this
disease,” said Rothstein, a professor of neurology and neuroscience
and director of the Robert Packard Center for ALS Research at Johns
Hopkins. “Importantly, this will serve as a scientifically rich
national resource for human ALS cell lines.”
ALS, also known as Lou Gehrig’s disease, is characterized by a
gradual loss of muscle strength and coordination. The disease is
fatal, with only about 20 percent of patients living more than five
years beyond diagnosis.
The funding for the Johns Hopkins work comes from an NIH Grand
Opportunities grant, part of the American Recovery and Reinvestment
Act of 2009. According to the NIH, the grants in this program
“provide investigators and institutions with the opportunity to
engage in new avenues of research with a high likelihood of
significant impact on growth and investment in biomedical or
behavioral research and development, public health and health care
delivery.”
“This program will provide the first national tissue resource of
real human ALS cells that could be used in projects ranging from
understanding the disease to the discovery of new effective
therapies,” Rothstein said. “By having a centralized, highly
characterized tissue resource, we can help catalyze research on this
disease nationally, and advance therapeutics.”
The award will be shared with three other laboratories, one at
Harvard University and two at Columbia University. The project will
create at least three new jobs in the labs at Johns Hopkins, as well
as multiple jobs at the collaborating sites, Rothstein said.
The Johns Hopkins team will collaborate with San Francisco–based
biopharmaceutical company iPierian, which specializes in working
with the novel stem cells to be used in this project. The stem cells,
known as induced pluripotent stem, or iPS cells, can develop into
cells that populate many organs but are derived from non-stem cells.
The scientists plan to grow iPS cells from ALS patients’ skin, then
steer them to develop into motor neurons and astrocytes, the two
types of nerve cells that are affected in ALS.
Previous studies of ALS have been hindered by the fact that
researchers can’t use patients’ actual neurons in studies. By
generating iPS cells, Rothstein and his colleagues hope to open up
new avenues for research and discovery.
Rothstein will be working with Johns Hopkins School of Medicine
colleagues Nicholas Maragakis, an associate professor of neurology,
and Dwight Bergles, an associate professor of neuroscience, who will
be analyzing the iPS cells for functional properties so the team
will know when they have succeeded in making an astrocyte before
providing the cells as a national resource.
Rothstein’s investigation is among the more than 340 stimulus-funded
research grants and supplements totaling more than $160.3 million
that Johns Hopkins has garnered since Congress passed the American
Recovery and Reinvestment Act of 2009 (informally known by the
acronym ARRA), bestowing the National Institutes of Health and the
National Science Foundation with $12.4 billion in extra money to
underwrite research grants by September 2010. The stimulus package—which
provided $550 billion in new spending, including the above grants—is
part of the federal government’s attempt to bring back a stumbling
economy by distributing dollars for transportation projects,
infrastructure building, the development of new energy sources and
job creation, and financing research that will benefit humankind.
Johns Hopkins scientists have submitted about 1,300 proposals for
stimulus-funded investigations, ranging from strategies to help
recovering addicts stay sober and the role that certain proteins
play in the development of muscular dystrophy to mouse studies
seeking to understand how men and women differ in their response to
the influenza virus.
To date, 112 jobs have been created at Johns Hopkins through ARRA
funding
Read more:
http://gazette.jhu.edu/2010/02/22/nih-grant-funds-study-on-stem-cells-from-als-patients/#ixzz0gSadkPJ1
study on stem cells from ALS patients
Lead researcher Jeffrey Rothstein,
right, and Nicholas Maragakis will provide the cells generated
in their program to other researchers nationwide. Photo: Will
Kirk/Homewoodphoto.jhu.edu
A two-year $3.7 million stimulus grant from the National
Institutes of Health will allow Johns Hopkins neurologist and lead
researcher Jeffrey Rothstein to expand on his long-standing research
into the nerve- and muscle-wasting disease amyotrophic lateral
sclerosis, or ALS.
Using stem cells developed in a laboratory from skin cell samples
taken from 20 ALS patients and five control subjects, Rothstein and
his colleagues will study the biology and chemistry involved in the
development and progression of the disease and will test drugs to
intervene in the process. When the two-year program is completed,
the cells generated will be available nationwide to other
researchers.
“We believe that the ability to work with the two types of cells
most relevant for ALS, developed directly from ALS patients, will
give us a tremendous boost toward understanding more about this
disease,” said Rothstein, a professor of neurology and neuroscience
and director of the Robert Packard Center for ALS Research at Johns
Hopkins. “Importantly, this will serve as a scientifically rich
national resource for human ALS cell lines.”
ALS, also known as Lou Gehrig’s disease, is characterized by a
gradual loss of muscle strength and coordination. The disease is
fatal, with only about 20 percent of patients living more than five
years beyond diagnosis.
The funding for the Johns Hopkins work comes from an NIH Grand
Opportunities grant, part of the American Recovery and Reinvestment
Act of 2009. According to the NIH, the grants in this program
“provide investigators and institutions with the opportunity to
engage in new avenues of research with a high likelihood of
significant impact on growth and investment in biomedical or
behavioral research and development, public health and health care
delivery.”
“This program will provide the first national tissue resource of
real human ALS cells that could be used in projects ranging from
understanding the disease to the discovery of new effective
therapies,” Rothstein said. “By having a centralized, highly
characterized tissue resource, we can help catalyze research on this
disease nationally, and advance therapeutics.”
The award will be shared with three other laboratories, one at
Harvard University and two at Columbia University. The project will
create at least three new jobs in the labs at Johns Hopkins, as well
as multiple jobs at the collaborating sites, Rothstein said.
The Johns Hopkins team will collaborate with San Francisco–based
biopharmaceutical company iPierian, which specializes in working
with the novel stem cells to be used in this project. The stem cells,
known as induced pluripotent stem, or iPS cells, can develop into
cells that populate many organs but are derived from non-stem cells.
The scientists plan to grow iPS cells from ALS patients’ skin, then
steer them to develop into motor neurons and astrocytes, the two
types of nerve cells that are affected in ALS.
Previous studies of ALS have been hindered by the fact that
researchers can’t use patients’ actual neurons in studies. By
generating iPS cells, Rothstein and his colleagues hope to open up
new avenues for research and discovery.
Rothstein will be working with Johns Hopkins School of Medicine
colleagues Nicholas Maragakis, an associate professor of neurology,
and Dwight Bergles, an associate professor of neuroscience, who will
be analyzing the iPS cells for functional properties so the team
will know when they have succeeded in making an astrocyte before
providing the cells as a national resource.
Rothstein’s investigation is among the more than 340 stimulus-funded
research grants and supplements totaling more than $160.3 million
that Johns Hopkins has garnered since Congress passed the American
Recovery and Reinvestment Act of 2009 (informally known by the
acronym ARRA), bestowing the National Institutes of Health and the
National Science Foundation with $12.4 billion in extra money to
underwrite research grants by September 2010. The stimulus package—which
provided $550 billion in new spending, including the above grants—is
part of the federal government’s attempt to bring back a stumbling
economy by distributing dollars for transportation projects,
infrastructure building, the development of new energy sources and
job creation, and financing research that will benefit humankind.
Johns Hopkins scientists have submitted about 1,300 proposals for
stimulus-funded investigations, ranging from strategies to help
recovering addicts stay sober and the role that certain proteins
play in the development of muscular dystrophy to mouse studies
seeking to understand how men and women differ in their response to
the influenza virus.
To date, 112 jobs have been created at Johns Hopkins through ARRA
funding
Read more:
http://gazette.jhu.edu/2010/02/22/nih-grant-funds-study-on-stem-cells-from-als-patients/#ixzz0gSadkPJ1
study on stem cells from ALS patients
Lead researcher Jeffrey Rothstein,
right, and Nicholas Maragakis will provide the cells generated
in their program to other researchers nationwide. Photo: Will
Kirk/Homewoodphoto.jhu.edu
A two-year $3.7 million stimulus grant from the National
Institutes of Health will allow Johns Hopkins neurologist and lead
researcher Jeffrey Rothstein to expand on his long-standing research
into the nerve- and muscle-wasting disease amyotrophic lateral
sclerosis, or ALS.
Using stem cells developed in a laboratory from skin cell samples
taken from 20 ALS patients and five control subjects, Rothstein and
his colleagues will study the biology and chemistry involved in the
development and progression of the disease and will test drugs to
intervene in the process. When the two-year program is completed,
the cells generated will be available nationwide to other
researchers.
“We believe that the ability to work with the two types of cells
most relevant for ALS, developed directly from ALS patients, will
give us a tremendous boost toward understanding more about this
disease,” said Rothstein, a professor of neurology and neuroscience
and director of the Robert Packard Center for ALS Research at Johns
Hopkins. “Importantly, this will serve as a scientifically rich
national resource for human ALS cell lines.”
ALS, also known as Lou Gehrig’s disease, is characterized by a
gradual loss of muscle strength and coordination. The disease is
fatal, with only about 20 percent of patients living more than five
years beyond diagnosis.
The funding for the Johns Hopkins work comes from an NIH Grand
Opportunities grant, part of the American Recovery and Reinvestment
Act of 2009. According to the NIH, the grants in this program
“provide investigators and institutions with the opportunity to
engage in new avenues of research with a high likelihood of
significant impact on growth and investment in biomedical or
behavioral research and development, public health and health care
delivery.”
“This program will provide the first national tissue resource of
real human ALS cells that could be used in projects ranging from
understanding the disease to the discovery of new effective
therapies,” Rothstein said. “By having a centralized, highly
characterized tissue resource, we can help catalyze research on this
disease nationally, and advance therapeutics.”
The award will be shared with three other laboratories, one at
Harvard University and two at Columbia University. The project will
create at least three new jobs in the labs at Johns Hopkins, as well
as multiple jobs at the collaborating sites, Rothstein said.
The Johns Hopkins team will collaborate with San Francisco–based
biopharmaceutical company iPierian, which specializes in working
with the novel stem cells to be used in this project. The stem cells,
known as induced pluripotent stem, or iPS cells, can develop into
cells that populate many organs but are derived from non-stem cells.
The scientists plan to grow iPS cells from ALS patients’ skin, then
steer them to develop into motor neurons and astrocytes, the two
types of nerve cells that are affected in ALS.
Previous studies of ALS have been hindered by the fact that
researchers can’t use patients’ actual neurons in studies. By
generating iPS cells, Rothstein and his colleagues hope to open up
new avenues for research and discovery.
Rothstein will be working with Johns Hopkins School of Medicine
colleagues Nicholas Maragakis, an associate professor of neurology,
and Dwight Bergles, an associate professor of neuroscience, who will
be analyzing the iPS cells for functional properties so the team
will know when they have succeeded in making an astrocyte before
providing the cells as a national resource.
Rothstein’s investigation is among the more than 340 stimulus-funded
research grants and supplements totaling more than $160.3 million
that Johns Hopkins has garnered since Congress passed the American
Recovery and Reinvestment Act of 2009 (informally known by the
acronym ARRA), bestowing the National Institutes of Health and the
National Science Foundation with $12.4 billion in extra money to
underwrite research grants by September 2010. The stimulus package—which
provided $550 billion in new spending, including the above grants—is
part of the federal government’s attempt to bring back a stumbling
economy by distributing dollars for transportation projects,
infrastructure building, the development of new energy sources and
job creation, and financing research that will benefit humankind.
Johns Hopkins scientists have submitted about 1,300 proposals for
stimulus-funded investigations, ranging from strategies to help
recovering addicts stay sober and the role that certain proteins
play in the development of muscular dystrophy to mouse studies
seeking to understand how men and women differ in their response to
the influenza virus.
To date, 112 jobs have been created at Johns Hopkins through ARRA
funding
Read more:
http://gazette.jhu.edu/2010/02/22/nih-grant-funds-study-on-stem-cells-from-als-patients/#ixzz0gSadkPJ1
study on stem cells from ALS patients
Lead researcher Jeffrey Rothstein,
right, and Nicholas Maragakis will provide the cells generated
in their program to other researchers nationwide. Photo: Will
Kirk/Homewoodphoto.jhu.edu
A two-year $3.7 million stimulus grant from the National
Institutes of Health will allow Johns Hopkins neurologist and lead
researcher Jeffrey Rothstein to expand on his long-standing research
into the nerve- and muscle-wasting disease amyotrophic lateral
sclerosis, or ALS.
Using stem cells developed in a laboratory from skin cell samples
taken from 20 ALS patients and five control subjects, Rothstein and
his colleagues will study the biology and chemistry involved in the
development and progression of the disease and will test drugs to
intervene in the process. When the two-year program is completed,
the cells generated will be available nationwide to other
researchers.
“We believe that the ability to work with the two types of cells
most relevant for ALS, developed directly from ALS patients, will
give us a tremendous boost toward understanding more about this
disease,” said Rothstein, a professor of neurology and neuroscience
and director of the Robert Packard Center for ALS Research at Johns
Hopkins. “Importantly, this will serve as a scientifically rich
national resource for human ALS cell lines.”
ALS, also known as Lou Gehrig’s disease, is characterized by a
gradual loss of muscle strength and coordination. The disease is
fatal, with only about 20 percent of patients living more than five
years beyond diagnosis.
The funding for the Johns Hopkins work comes from an NIH Grand
Opportunities grant, part of the American Recovery and Reinvestment
Act of 2009. According to the NIH, the grants in this program
“provide investigators and institutions with the opportunity to
engage in new avenues of research with a high likelihood of
significant impact on growth and investment in biomedical or
behavioral research and development, public health and health care
delivery.”
“This program will provide the first national tissue resource of
real human ALS cells that could be used in projects ranging from
understanding the disease to the discovery of new effective
therapies,” Rothstein said. “By having a centralized, highly
characterized tissue resource, we can help catalyze research on this
disease nationally, and advance therapeutics.”
The award will be shared with three other laboratories, one at
Harvard University and two at Columbia University. The project will
create at least three new jobs in the labs at Johns Hopkins, as well
as multiple jobs at the collaborating sites, Rothstein said.
The Johns Hopkins team will collaborate with San Francisco–based
biopharmaceutical company iPierian, which specializes in working
with the novel stem cells to be used in this project. The stem
cells, known as induced pluripotent stem, or iPS cells, can develop
into cells that populate many organs but are derived from non-stem
cells. The scientists plan to grow iPS cells from ALS patients’
skin, then steer them to develop into motor neurons and astrocytes,
the two types of nerve cells that are affected in ALS.
Previous studies of ALS have been hindered by the fact that
researchers can’t use patients’ actual neurons in studies. By
generating iPS cells, Rothstein and his colleagues hope to open up
new avenues for research and discovery.
Rothstein will be working with Johns Hopkins School of Medicine
colleagues Nicholas Maragakis, an associate professor of neurology,
and Dwight Bergles, an associate professor of neuroscience, who will
be analyzing the iPS cells for functional properties so the team
will know when they have succeeded in making an astrocyte before
providing the cells as a national resource.
Rothstein’s investigation is among the more than 340
stimulus-funded research grants and supplements totaling more than
$160.3 million that Johns Hopkins has garnered since Congress passed
the American Recovery and Reinvestment Act of 2009 (informally known
by the acronym ARRA), bestowing the National Institutes of Health
and the National Science Foundation with $12.4 billion in extra
money to underwrite research grants by September 2010. The stimulus
package—which provided $550 billion in new spending, including the
above grants—is part of the federal government’s attempt to bring
back a stumbling economy by distributing dollars for transportation
projects, infrastructure building, the development of new energy
sources and job creation, and financing research that will benefit
humankind.
Johns Hopkins scientists have submitted about 1,300 proposals for
stimulus-funded investigations, ranging from strategies to help
recovering addicts stay sober and the role that certain proteins
play in the development of muscular dystrophy to mouse studies
seeking to understand how men and women differ in their response to
the influenza virus.
To date, 112 jobs have been created at Johns Hopkins through ARRA
funding
Read more:
http://gazette.jhu.edu/2010/02/22/nih-grant-funds-study-on-stem-cells-from-als-patients/#ixzz0gSadkPJ1
study on stem cells from ALS patients
Lead researcher Jeffrey Rothstein,
right, and Nicholas Maragakis will provide the cells generated
in their program to other researchers nationwide. Photo: Will
Kirk/Homewoodphoto.jhu.edu
A two-year $3.7 million stimulus grant from the National
Institutes of Health will allow Johns Hopkins neurologist and lead
researcher Jeffrey Rothstein to expand on his long-standing research
into the nerve- and muscle-wasting disease amyotrophic lateral
sclerosis, or ALS.
Using stem cells developed in a laboratory from skin cell samples
taken from 20 ALS patients and five control subjects, Rothstein and
his colleagues will study the biology and chemistry involved in the
development and progression of the disease and will test drugs to
intervene in the process. When the two-year program is completed,
the cells generated will be available nationwide to other
researchers.
“We believe that the ability to work with the two types of cells
most relevant for ALS, developed directly from ALS patients, will
give us a tremendous boost toward understanding more about this
disease,” said Rothstein, a professor of neurology and neuroscience
and director of the Robert Packard Center for ALS Research at Johns
Hopkins. “Importantly, this will serve as a scientifically rich
national resource for human ALS cell lines.”
ALS, also known as Lou Gehrig’s disease, is characterized by a
gradual loss of muscle strength and coordination. The disease is
fatal, with only about 20 percent of patients living more than five
years beyond diagnosis.
The funding for the Johns Hopkins work comes from an NIH Grand
Opportunities grant, part of the American Recovery and Reinvestment
Act of 2009. According to the NIH, the grants in this program
“provide investigators and institutions with the opportunity to
engage in new avenues of research with a high likelihood of
significant impact on growth and investment in biomedical or
behavioral research and development, public health and health care
delivery.”
“This program will provide the first national tissue resource of
real human ALS cells that could be used in projects ranging from
understanding the disease to the discovery of new effective
therapies,” Rothstein said. “By having a centralized, highly
characterized tissue resource, we can help catalyze research on this
disease nationally, and advance therapeutics.”
The award will be shared with three other laboratories, one at
Harvard University and two at Columbia University. The project will
create at least three new jobs in the labs at Johns Hopkins, as well
as multiple jobs at the collaborating sites, Rothstein said.
The Johns Hopkins team will collaborate with San Francisco–based
biopharmaceutical company iPierian, which specializes in working
with the novel stem cells to be used in this project. The stem
cells, known as induced pluripotent stem, or iPS cells, can develop
into cells that populate many organs but are derived from non-stem
cells. The scientists plan to grow iPS cells from ALS patients’
skin, then steer them to develop into motor neurons and astrocytes,
the two types of nerve cells that are affected in ALS.
Previous studies of ALS have been hindered by the fact that
researchers can’t use patients’ actual neurons in studies. By
generating iPS cells, Rothstein and his colleagues hope to open up
new avenues for research and discovery.
Rothstein will be working with Johns Hopkins School of Medicine
colleagues Nicholas Maragakis, an associate professor of neurology,
and Dwight Bergles, an associate professor of neuroscience, who will
be analyzing the iPS cells for functional properties so the team
will know when they have succeeded in making an astrocyte before
providing the cells as a national resource.
Rothstein’s investigation is among the more than 340
stimulus-funded research grants and supplements totaling more than
$160.3 million that Johns Hopkins has garnered since Congress passed
the American Recovery and Reinvestment Act of 2009 (informally known
by the acronym ARRA), bestowing the National Institutes of Health
and the National Science Foundation with $12.4 billion in extra
money to underwrite research grants by September 2010. The stimulus
package—which provided $550 billion in new spending, including the
above grants—is part of the federal government’s attempt to bring
back a stumbling economy by distributing dollars for transportation
projects, infrastructure building, the development of new energy
sources and job creation, and financing research that will benefit
humankind.
Johns Hopkins scientists have submitted about 1,300 proposals for
stimulus-funded investigations, ranging from strategies to help
recovering addicts stay sober and the role that certain proteins
play in the development of muscular dystrophy to mouse studies
seeking to understand how men and women differ in their response to
the influenza virus.
To date, 112 jobs have been created at Johns Hopkins through ARRA
funding
Read more:
http://gazette.jhu.edu/2010/02/22/nih-grant-funds-study-on-stem-cells-from-als-patients/#ixzz0gSadkPJ1
NIH grant funds study on stem cells from ALS patients
February 22, 2010
By
Amy Lunday and Christen Brownlee
Homewood and Johns Hopkins Medicine
Filed under
ARRA Research,
Divisions,
Research,
School of Medicine
Lead researcher
Jeffrey Rothstein, right, and Nicholas Maragakis will provide the cells
generated in their program to other researchers nationwide. Photo: Will
Kirk/Homewoodphoto.jhu.edu
A two-year $3.7 million stimulus grant from the National Institutes of
Health will allow Johns Hopkins neurologist and lead researcher Jeffrey
Rothstein to expand on his long-standing research into the nerve and
muscle-wasting disease amyotrophic lateral sclerosis, or ALS.
Using
stem cells developed in a laboratory from skin cell samples taken from 20
ALS patients and five control subjects, Rothstein and his colleagues will
study the biology and chemistry involved in the development and progression
of the disease and will test drugs to intervene in the process. When the
two-year program is completed, the cells generated will be available
nationwide to other researchers.
“We
believe that the ability to work with the two types of cells most relevant
for ALS, developed directly from ALS patients, will give us a tremendous
boost toward understanding more about this disease,” said Rothstein, a
professor of neurology and neuroscience and director of the Robert Packard
Center for ALS Research at Johns Hopkins. “Importantly, this will serve as a
scientifically rich national resource for human ALS cell lines.”
ALS,
also known as Lou Gehrig’s disease, is characterized by a gradual loss of
muscle strength and coordination. The disease is fatal, with only about 20
percent of patients living more than five years beyond diagnosis.
The
funding for the Johns Hopkins work comes from an NIH Grand Opportunities
grant, part of the American Recovery and Reinvestment Act of 2009. According
to the NIH, the grants in this program “provide investigators and
institutions with the opportunity to engage in new avenues of research with
a high likelihood of significant impact on growth and investment in
biomedical or behavioral research and development, public health and health
care delivery.”
“This
program will provide the first national tissue resource of real human ALS
cells that could be used in projects ranging from understanding the disease
to the discovery of new effective therapies,” Rothstein said. “By having a
centralized, highly characterized tissue resource, we can help catalyze
research on this disease nationally, and advance therapeutics.”
The
award will be shared with three other laboratories, one at Harvard
University and two at Columbia University. The project will create at least
three new jobs in the labs at Johns Hopkins, as well as multiple jobs at the
collaborating sites, Rothstein said.
The
Johns Hopkins team will collaborate with San Francisco–based
biopharmaceutical company iPierian, which specializes in working with the
novel stem cells to be used in this project. The stem cells, known as
induced pluripotent stem, or iPS cells, can develop into cells that populate
many organs but are derived from non-stem cells. The scientists plan to grow
iPS cells from ALS patients’ skin, then steer them to develop into motor
neurons and astrocytes, the two types of nerve cells that are affected in
ALS.
Previous studies of ALS have been hindered by the fact that researchers
can’t use patients’ actual neurons in studies. By generating iPS cells,
Rothstein and his colleagues hope to open up new avenues for research and
discovery.
Rothstein will be working with Johns Hopkins School of Medicine colleagues
Nicholas Maragakis, an associate professor of neurology, and Dwight Bergles,
an associate professor of neuroscience, who will be analyzing the iPS cells
for functional properties so the team will know when they have succeeded in
making an astrocyte before providing the cells as a national resource.
Rothstein’s investigation is among the more than 340 stimulus-funded
research grants and supplements totaling more than $160.3 million that Johns
Hopkins has garnered since Congress passed the American Recovery and
Reinvestment Act of 2009 (informally known by the acronym ARRA), bestowing
the National Institutes of Health and the National Science Foundation with
$12.4 billion in extra money to underwrite research grants by September
2010. The stimulus package—which provided $550 billion in new spending,
including the above grants—is part of the federal government’s attempt to
bring back a stumbling economy by distributing dollars for transportation
projects, infrastructure building, the development of new energy sources and
job creation, and financing research that will benefit humankind.
Johns
Hopkins scientists have submitted about 1,300 proposals for stimulus-funded
investigations, ranging from strategies to help recovering addicts stay
sober and the role that certain proteins play in the development of muscular
dystrophy to mouse studies seeking to understand how men and women differ in
their response to the influenza virus.
To
date, 112 jobs have been created at Johns Hopkins through ARRA funding.
http://mdn.mainichi.jp/mdnnews/news/20100223p2a00m0na016000c.html
Researchers use 'buckyballs' to successfully introduce genetic material into
the body
A research team has succeeded in binding genes to nanometric carbon
molecules to introduce genetic material into the body, a technique that
could be used in gene therapy.
The University of Tokyo team led by professor of organic chemistry Eiichi
Nakamura inserted the gene for the production of insulin into diabetic mice,
and confirmed that the mice's blood sugar declined after the treatment.
The researchers altered spherical carbon molecules called fullerenes -- or
buckyballs, as they are also known -- which genetic material binds to easily.
The carbon molecules attach themselves to the outside of the genes, creating
what the researchers believe is like a suit of armor that protects them once
inside the body. The team injected the buckyballs and their genetic cargo
into the mice, and confirmed that the genetic material had become active in
the mice's lungs, liver and spleen.
When the researchers bound the gene for insulin production to the buckyballs,
they found the genes had made their way into the cells of the liver and
other organs, resulting in the blood sugar reduction. The researchers have
not observed any side effects in the mice from the treatments so far.
Nakamura's team's results were to be published in the online version of the
U.S. Proceedings of the National Academy of Sciences on Tuesday.
http://theses.ulb.ac.be/ETD-db/collection/available/ULBetd-01152010-173759/
Auteur Rai, Myriam (myriam.rai@ulb.ac.be)
Titre Overcoming frataxin gene silencing in Friedreich’s ataxia with small
molecules: studies on cellular and animal models
Département F204 - Faculté de médecine - Sciences biomédicales
Intitulé du diplôme Doctorat en sciences biomédicales
Date de défense 2010-01-05
Jury Abramowicz, Marc (Membre du jury/Committee Member)
Dan, Bernard (Membre du jury/Committee Member)
Festenstein, Richard (Membre du jury/Committee Member)
Fuks, François (Membre du jury/Committee Member)
Koenig, Michel (Membre du jury/Committee Member)
Lebrun, Philippe (Président du jury/Committee Chair)
Pandolfo, Massimo (Promoteur/Director)
Mots-clés frataxin, Friedreich's ataxia, chromatin, biomarker, histone
deacetylase inhibitor
--------------------------------------------------------------------------------
Résumé Friedreich’s ataxia (FRDA) is an inherited recessive disorder
characterized by progressive neurological disability and heart disease. It
is caused by a pathological intronic hyperexpansion of a GAA repeat in the
FXN gene, encoding the essential mitochondrial protein frataxin. At the
homozygous state, the GAA expansion induces a heterochromatin state with
decreased histone acetylation and increased methylation, resulting in a
partial deficiency of frataxin expression. This was established in cells
from FRDA patients. We showed that the same chromatin changes exist in a GAA
based mouse model, KIKI, generated in our laboratory. Furthermore, treatment
of KIKI mice with a novel Histone Deacetylase Inhibitor (HDACi), 106, a
pimelic diphenylamide that increases frataxin levels in FRDA cell culture,
restored frataxin levels in the nervous system and heart of KIKI mice and
induced histone hyperacetylation near the GAA repeat. As shown by
microarrays, most of the differentially expressed genes in KIKI were
corrected towards wild type. In an effort to improve the pharmacological
profile of compound 106, we synthesized more compounds based on its
structure and specificity. We characterized two of these compounds in FRDA
patients’ peripheral blood lymphocytes and in the KIKI mouse model. We
observed a sustained frataxin upregulation in both systems, and, by
following the time course of the events, we concluded that the effects of
these compounds last longer than the time of direct exposure to HDACi. Our
results support the pre-clinical development of a therapeutic approach based
on pimelic diphenylamide HDACis for FRDA. Laboratory tools to follow disease
progression and assess drug efficacy are needed in a slowly progressive
neurodegenerative disease such as FRDA. We used microarrays to characterize
the gene expression profile in peripheral lymphocytes from FRDA patients,
carriers and controls. We identified gene expression changes in heterozygous,
clinically unaffected GAA expansion carriers, suggesting that they present a
biochemical phenotype, consistent with data from animal models of frataxin
deficiency. We identified a subset of genes changing in patients as a result
of pathological frataxin deficiency establishing robust gene expression
changes in peripheral lymphocytes. These changes can be used as a biomarker
to monitor disease progression and potentially assess drug efficacy. To this
end, we used he same methodology to characterize the gene expression
profiles in peripheral lymphocytes after treatment with pimelic
diphenylamide HDACi. This treatment had relevant effects on gene expression
on peripheral patients’ blood lymphocytes. It increased frataxin levels in a
dose-dependent manner, and partially rescued the gene expression phenotype
associated with frataxin deficiency in the tested cell model, thus providing
the first application of a biomarker gene set in FRDA.
http://www.sciencedaily.com/releases/2010/01/100124162149.htm
Illuminating Protein Networks in One Step
ScienceDaily (Jan. 31, 2010) — A new assay capable of examining hundreds of
proteins at once and enabling new experiments that could dramatically change
our understanding of cancer and other diseases has been invented by a team
of University of Chicago scientists.
Described January 24 in the journal Nature Methods, the new micro-western
arrays combine the specificity of the popular "Western blot" protein assay
with the large scale of DNA microarrays. The technique will allow scientists
to observe much of a cell's intricate protein network in one experiment
rather than peeking at one small piece at a time.
"The proteins are the actual machines that are doing everything in the cell,
but nobody's been able to examine them in depth because it's been too
complicated. Now, we can begin to do that with this new method," said
Richard B. Jones, senior author and assistant professor at and the
University of Chicago's Ben May Department for Cancer Research and the
Institute for Genomics and Systems Biology.
Since the 1970's, laboratories have used Western blots to measure proteins.
Cellular material is loaded into a gel and proteins of different sizes are
separated by an electric field. A protein is then targeted by an antibody,
allowing scientists to measure the amount present in the cells.
The method has led to numerous findings across the field of cell biology,
but is limited by a need for large amounts of cell material and expensive
antibodies, and the inability to measure more than a handful of proteins at
a time. With hundreds or even thousands of proteins involved in cellular
networks, scientists were restricted to observing only a small fraction of
protein activity with each experiment.
"When you walk into a dark room and don't have much information, it's
difficult to predict where everything is going to be," Jones said. "If
someone can simply turn on the light, you don't have to progress one step at
a time by bumping into things. With this new technology, you can potentially
see everything at the same time."
Micro-western arrays adapt the technology of the micro-array, typically used
to assess the expression of thousands of genes in a single experiment, to
proteins. With pre-printed micro-western array gels, essentially comprising
96 miniature Western blots, scientists can compare the levels of hundreds of
proteins simultaneously, or compare dozens of proteins under dozens of
treatment conditions in one shot. Mere nanoliters of cell material and
antibodies are needed for the experiments, reducing cost and maximizing the
information obtained from a single sample.
To demonstrate the potential of the micro-western array, Jones and
colleagues from the University of Chicago and the Massachusetts Institute of
Technology looked at the behavior of proteins in a cancer cell line with
elevated amounts of epidermal growth factor receptor (EGFR).
"We started asking questions about what we could do that no one else could
previously do," Jones said. "We could actually reproducibly see 120 things
at a time rather than looking at 1 or 2 or 5."
The experiments found that activating EGFR simultaneously activated several
other receptors in the cell -- a new discovery that may explain why some
tumors become resistant to cancer therapies.
With more information, the method may potentially be used clinically for
more precise diagnoses of cancer and other diseases that can direct
individualized treatment.
"In the clinic, you're limited by the fact that typically most cancers are
diagnosed by one or two markers; you're looking for one or two markers that
are high or low then trying to diagnose and treat an illness," Jones said. "Here,
we can potentially measure a collection of proteins at the same time and not
just focus on one guess. We've never been able do that before."
Other scientists in the field of systems biology said that micro-western
arrays would make possible experiments that were previously beyond the scope
of laboratory methods.
"I think this is really a breakthrough technology that allows us to monitor
in close to real time the activity profiles of modified signaling proteins,
which is essentially impossible right now," said Andrea Califano, professor
of biomedical informatics at Columbia University. "This opens up a
completely new window in terms of the molecular profiling of the cell."
"One of the biggest hurdles for systems biology is the struggle for high
density, dynamic and quantitative data, and the micro-western array method
will go a long way to address this problem," said Walter Kolch, director of
Systems Biology Ireland and Professor at University College Dublin. "It is a
fine example of generating exciting new technology from applying a new idea
to an old method."
The work was funded by The University of Chicago Comprehensive Cancer Center,
the American Cancer Society, the Cancer Research Foundation, the Illinois
Department of Public Health, the National Institutes of General Medical
Sciences, the National Cancer Institute, and the National Science Foundation.
Skin cells turned directly into
neurons
By Clive Cookson
Published: January 28 2010 02:00 | Last updated: January 28 2010 02:00
Stem cell scientists at Stanford University in California announced "a huge
step forward" last night, with the publication of research that turned skin
into nerve cells without any intermediate step.
The production of neurons [nerve cells] directly from other adult cells,
without making stem cells en route, could transform "regenerative medicine"
- providing a plentiful supply of neurons for treating people with
degenerative brain diseases such as Parkinson's or those with spinal
injuries.
"We actively and directly induced one cell type to become a completely
different cell type," said Marius Wernig of Stanford's Institute for Stem
Cell Biology and Regenerative Medicine. "These are fully functional neurons.
They can do all the principal things that neurons in the brain do."
This includes making connections with and signalling to other nerve cells -
critical functions if the cells are eventually to be used as therapy for
brain disease. The study is published online in the journal Nature .
Although research had suggested that specialised cells could be coaxed to
show properties of other cell types, this is the first time skin cells have
been converted into neurons in a laboratory.
The change happened within a week of treating mouse skin cells with a
mixture of three genes, with an efficiency of up to nearly 20 per cent. The
scientists are now working to duplicate the feat with human cells.
Until recently, scientists believed cellular differentiation was a one-way
process, with primitive and versatile embryonic stem cells giving rise to
all the body's more specialised cells.
Then, in 2007 they discovered how to turn the clock back, reversing the
specialisation process by converting adult cells to "induced pluripotent
stem cells", which could then become a different type of cell.
The latest discovery shows that this intermediate step is unnecessary. But
many years of work will be needed before direct conversion reaches the
clinic.
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