Tuesday, October 21, 2008
A small antibody fragment that is highly effective in neutralizing the human immunodeficiency virus (HIV) by preventing the virus from entering cells has been identified by researchers at the National Cancer Institute (NCI), part of the National Institutes of Health (NIH). This finding may provide insight into the development of new treatments against HIV and other viruses, hopefully in the not too distant future. The study appeared online Oct. 20, 2008, in Proceedings of the National Academy of Sciences.
Treating HIV-infected individuals is difficult because the virus is able to mutate and become resistant to antiretroviral drugs. "In the United States, it is estimated that more than 50 percent of patients who are receiving antiretroviral therapy for their HIV infection carry strains of the virus that are resistant to treatment with at least one of the currently available antiretroviral drugs," said NCI Director John E. Niederhuber, M.D. "The development of new drugs against HIV is an urgent public health need."
Antibodies are large proteins naturally produced by the immune system to help fight disease-causing foreign invaders, such as viruses and bacteria. Although the general structure of all antibodies is very similar, a small region at the tip of the protein is extremely variable, allowing millions of antibodies, characterized by slightly different tip structures, to exist and bind to different targets, known as antigens. Previous research has shown that reducing antibodies to the smallest independently functional fragment, known as a variable domain, can extend their utility as therapeutic agents. These fragments, called domain antibodies (dAbs), retain the variable tip structure and, therefore, the antigen-binding specificity of the parent antibody. Because of their small size, they are able to access targets that cannot be reached by much larger, whole antibodies.
In an earlier study, the researchers identified a unique antibody, called m0, while screening a large library of antibodies against the HIV protein, Env (also known as gp120). The library contained the variable portions of antibodies that can bind to Env antigens. "We found an antibody fragment that exhibited the ability to neutralize HIV and had properties that allowed us to construct a novel library containing dAbs directed against HIV," said Dimiter S. Dimitrov, Ph.D., of NCI's Center for Cancer Research.
Based on m0's framework, the leading author of the study, Weizao Chen, Ph.D., constructed a very large library of dAbs (25 billion different dAbs), screened it against Env proteins from two different strains of HIV, and identified a dAb, m36, that bound strongly to different Env proteins and blocked the infectivity of a broad range of HIV strains. The researchers believe that m36 represents the first human dAb against HIV reported.
"The antibody fragment that we identified, m36, could have potential in the development of a therapeutic that inhibits HIV," said Dimitrov. "Further research with this molecule also could offer insight about how the virus infects cells and how it evades neutralization by the immune system."
The research team is working to test various combinations of m36 with other inhibitors that may be effective against HIV. The team is also attempting to construct more potent versions of m36. Partnership with industry could speed the ability to evaluate m36 as a potential treatment for HIV. Dimitrov's team is also using this approach to identify dAbs against cancer and other disease-related antigens.
Treating HIV-infected individuals is difficult because the virus is able to mutate and become resistant to antiretroviral drugs. "In the United States, it is estimated that more than 50 percent of patients who are receiving antiretroviral therapy for their HIV infection carry strains of the virus that are resistant to treatment with at least one of the currently available antiretroviral drugs," said NCI Director John E. Niederhuber, M.D. "The development of new drugs against HIV is an urgent public health need."
Antibodies are large proteins naturally produced by the immune system to help fight disease-causing foreign invaders, such as viruses and bacteria. Although the general structure of all antibodies is very similar, a small region at the tip of the protein is extremely variable, allowing millions of antibodies, characterized by slightly different tip structures, to exist and bind to different targets, known as antigens. Previous research has shown that reducing antibodies to the smallest independently functional fragment, known as a variable domain, can extend their utility as therapeutic agents. These fragments, called domain antibodies (dAbs), retain the variable tip structure and, therefore, the antigen-binding specificity of the parent antibody. Because of their small size, they are able to access targets that cannot be reached by much larger, whole antibodies.
In an earlier study, the researchers identified a unique antibody, called m0, while screening a large library of antibodies against the HIV protein, Env (also known as gp120). The library contained the variable portions of antibodies that can bind to Env antigens. "We found an antibody fragment that exhibited the ability to neutralize HIV and had properties that allowed us to construct a novel library containing dAbs directed against HIV," said Dimiter S. Dimitrov, Ph.D., of NCI's Center for Cancer Research.
Based on m0's framework, the leading author of the study, Weizao Chen, Ph.D., constructed a very large library of dAbs (25 billion different dAbs), screened it against Env proteins from two different strains of HIV, and identified a dAb, m36, that bound strongly to different Env proteins and blocked the infectivity of a broad range of HIV strains. The researchers believe that m36 represents the first human dAb against HIV reported.
"The antibody fragment that we identified, m36, could have potential in the development of a therapeutic that inhibits HIV," said Dimitrov. "Further research with this molecule also could offer insight about how the virus infects cells and how it evades neutralization by the immune system."
The research team is working to test various combinations of m36 with other inhibitors that may be effective against HIV. The team is also attempting to construct more potent versions of m36. Partnership with industry could speed the ability to evaluate m36 as a potential treatment for HIV. Dimitrov's team is also using this approach to identify dAbs against cancer and other disease-related antigens.
Wednesday, October 15, 2008
It is well known that exercise is an important part of a healthy lifestyle but can exercise programs actually reduce the likelihood of drug abuse and thus prevent addiction? The National Institute on Drug Abuse (NIDA), part of the National Institutes of Health (NIH), is holding a seminal conference on June 5-6 to explore a possible role for physical activity in substance abuse prevention. As part of this effort, NIDA announced a $4 million grant initiative to spur further research on this emerging area of investigation.
"Exercise has been shown to be beneficial in so many areas of physical and mental health," said Dr. Nora Volkow, NIDA Director. "This cross-disciplinary meeting is designed to get scientists thinking creatively about its potential role in substance abuse prevention."
More than 100 scientists from around the country are gathering for the two-day conference. The goals of the meeting are:
* To share the state of the science in epidemiology, basic science, and intervention research-focused on physical activity as a strategy to prevent substance abuse;
* To facilitate development and testing of new paradigms for prevention; and
* To promote future research in these areas.
Presentations will focus on the importance of the social context in which physical activity occurs, including school and the natural environment, as well as the relationship of physical activity to physical disorders (obesity), social reward structures (motivation), cognition (attention, impulse control and other motor skills), and mood disorders (depression, stress), all of which may play a role in substance abuse. To facilitate research on the role of exercise, attendees will also learn about and see demonstrations of tools that assess physiological responses to exercise and physical activity.
The meeting is taking place on the NIH campus, and will include participants from several other NIH institutes as well as experts from around the world. On the second day of the meeting, Sally Squires, the author of the Washington PostOs Lean Plate Club will share insights and feedback from her column on what the public wants to know about physical activity and health.
A full agenda and speaker list is available at: www.sei2003.com/NIDA/1014032/index.htm
"Exercise has been shown to be beneficial in so many areas of physical and mental health," said Dr. Nora Volkow, NIDA Director. "This cross-disciplinary meeting is designed to get scientists thinking creatively about its potential role in substance abuse prevention."
More than 100 scientists from around the country are gathering for the two-day conference. The goals of the meeting are:
* To share the state of the science in epidemiology, basic science, and intervention research-focused on physical activity as a strategy to prevent substance abuse;
* To facilitate development and testing of new paradigms for prevention; and
* To promote future research in these areas.
Presentations will focus on the importance of the social context in which physical activity occurs, including school and the natural environment, as well as the relationship of physical activity to physical disorders (obesity), social reward structures (motivation), cognition (attention, impulse control and other motor skills), and mood disorders (depression, stress), all of which may play a role in substance abuse. To facilitate research on the role of exercise, attendees will also learn about and see demonstrations of tools that assess physiological responses to exercise and physical activity.
The meeting is taking place on the NIH campus, and will include participants from several other NIH institutes as well as experts from around the world. On the second day of the meeting, Sally Squires, the author of the Washington PostOs Lean Plate Club will share insights and feedback from her column on what the public wants to know about physical activity and health.
A full agenda and speaker list is available at: www.sei2003.com/NIDA/1014032/index.htm
Monday, October 6, 2008
A directory listing 100 of the most prestigious health and social care researchers has been published by the National Institute for Health Research (NIHR) today.
The Directory lists Senior Investigators who have been chosen to support the people making the most outstanding contribution to patient and people-focused health research. In addition to their research, Senior Investigators will give new leadership to the NIHR Faculty, expert advice to the Director of the NIHR, act as NIHR ambassadors and promote clinical and applied people-focused research in health and social care.
The NIHR Senior Investigators, who feature in the directory published today, lead some of the most prestigious applied health and social care research projects in the country. The importance of their work has been highlighted by the Prime Minister.
Prime Minister Gordon Brown said:
"I want Britain to lead the world in beating the diseases which cause such heartbreak for families. Over the last few years we have made major breakthroughs in research relevant to cancer, Alzheimer's, Parkinson's and strokes and many more - but these have yet to be turned into treatments from which we can all benefit. So let me tell you today that the unprecedented £15 billion we are investing in medical research will be directed to turning the major advances of the past few years into actual treatments and cures for NHS patients."
The research led by the NIHR Senior Investigators targets significant health issues which affect large numbers of the UK population. These include cancer, mental health, obesity, diabetes and cardiovascular disease.
Professor Sally C. Davies, Director General of Research and Development at the Department of Health said:
"The NIHR wants to support and encourage the people who are leading clinical and applied health research that is of direct relevance to the needs of the people of this country".
Today's announcement is in line with the National Ambition for Translational Health Research - the ability to make research move forward into excellent health practice. The UK is widely regarded as having some of the strongest basic medical research in the world. It generates 13.7 per cent of world citations, second only to the US and has thriving research communities in the private and university sectors.
The ways of ensuring that this happens are:
* A greater strategic focus - to ensure coordination of the government health research strategy, communicate the UK's National Ambitions, and encourage a stronger partnership between Government, health industries and charities.
* A research focused NHS - key steps in implementing this have included setting up NIHR clinical research networks to support clinical trials throughout England, and promote patient and public involvement in health research.
* Cross-government support - the government has established a cross-cutting PSA (public service agreement) to "promote world class science and innovation in the UK" and set up (in 2002) Research Councils UK (RCUK), a strategic partnership of the UK's seven Research Councils.
The Directory lists Senior Investigators who have been chosen to support the people making the most outstanding contribution to patient and people-focused health research. In addition to their research, Senior Investigators will give new leadership to the NIHR Faculty, expert advice to the Director of the NIHR, act as NIHR ambassadors and promote clinical and applied people-focused research in health and social care.
The NIHR Senior Investigators, who feature in the directory published today, lead some of the most prestigious applied health and social care research projects in the country. The importance of their work has been highlighted by the Prime Minister.
Prime Minister Gordon Brown said:
"I want Britain to lead the world in beating the diseases which cause such heartbreak for families. Over the last few years we have made major breakthroughs in research relevant to cancer, Alzheimer's, Parkinson's and strokes and many more - but these have yet to be turned into treatments from which we can all benefit. So let me tell you today that the unprecedented £15 billion we are investing in medical research will be directed to turning the major advances of the past few years into actual treatments and cures for NHS patients."
The research led by the NIHR Senior Investigators targets significant health issues which affect large numbers of the UK population. These include cancer, mental health, obesity, diabetes and cardiovascular disease.
Professor Sally C. Davies, Director General of Research and Development at the Department of Health said:
"The NIHR wants to support and encourage the people who are leading clinical and applied health research that is of direct relevance to the needs of the people of this country".
Today's announcement is in line with the National Ambition for Translational Health Research - the ability to make research move forward into excellent health practice. The UK is widely regarded as having some of the strongest basic medical research in the world. It generates 13.7 per cent of world citations, second only to the US and has thriving research communities in the private and university sectors.
The ways of ensuring that this happens are:
* A greater strategic focus - to ensure coordination of the government health research strategy, communicate the UK's National Ambitions, and encourage a stronger partnership between Government, health industries and charities.
* A research focused NHS - key steps in implementing this have included setting up NIHR clinical research networks to support clinical trials throughout England, and promote patient and public involvement in health research.
* Cross-government support - the government has established a cross-cutting PSA (public service agreement) to "promote world class science and innovation in the UK" and set up (in 2002) Research Councils UK (RCUK), a strategic partnership of the UK's seven Research Councils.
