Computational Medicine Begins to Enhance the Way Doctors Detect and Treat Disease

Many challenges must still be overcome before computational medicine becomes a routine part of patient care

Computational medicine, a fast-growing method of using computer models and sophisticated software to figure out how disease develops–and how to thwart it–has begun to leap off the drawing board and land in the hands of doctors who treat patients for heart ailments, cancer and other illnesses. Using digital tools, researchers have begun to use experimental and clinical data to build models that can unravel complex medical mysteries.

These are some of the conclusions of a new review of the field published in the Oct. 31 issue of the journal Science Translational Medicine. The article, “Computational Medicine: Translating Models to Clinical Care,” was written by four Johns Hopkins professors affiliated with the university’s Institute for Computational Medicine.

The institute was launched in 2005 as collaboration between the university’s Whiting School of Engineering and its School of Medicine. The goal was to use powerful computers to analyze and mathematically model disease mechanisms. The results were to be used to help predict who is at risk of developing a disease and to determine how to treat it more effectively.

In recent years, “The field has exploded. There is a whole new community of people being trained in mathematics, computer science and engineering, and they are being cross-trained in biology,” said institute director Raimond Winslow. “This allows them to bring a whole new perspective to medical diagnosis and treatment. Engineers traditionally construct models of the systems they are designing. In our case, we’re building computational models of what we trying to study, which is disease.”

Looking at disease through the lens of traditional biology is like trying to assemble a very complex jigsaw puzzle with a huge number of pieces, he said. The result can be a very incomplete picture. “Computational medicine can help you see how the pieces of the puzzle fit together to give a more holistic picture,” Winslow said. “We may never have all of the missing pieces, but we’ll wind up with a much clearer view of what causes disease and how to treat it.”

Biology in both health and disease is very complex, Winslow added. It involves the feed-forward flow of information from the level of the gene to protein, networks, cells, organs and organ systems. This is already complex, he said, and to make matters even more difficult, it also involves feed-back pathways by which, for example, proteins, mechanical forces at the level of tissues and organs, and environmental factors regulate function at lower levels such as the gene.

Computational models, Winslow said, help us to understand these complex interactions, the nature of which is often highly complex and non-intuitive. Models like these allow researchers to understand disease mechanisms, aid in diagnosis, and test the effectiveness of different therapies. By using computer models, he said, potential therapies can be tested “In Silico” at high speed.  The results can then be used to guide further experiments to gather new data to refine the models until they are highly predictive.

“Our intent in writing this journal article was to open the eyes of physicians and medical researchers who are unfamiliar with the field of computational medicine,” said Winslow, who is first author of the Science Translational Medicine overview. He also wanted to describe examples of computational medicine that are making their way out of research labs and into clinics where patients are being treated. “This transition,” he said, “is already under way.”

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via John Hopkins University
 

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New Vaccine for Nicotine Addiction

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Weill Cornell Researchers Develop Novel Anti-Body Vaccine that Blocks Addictive Nicotine Chemicals from Reaching the Brain

Researchers at Weill Cornell Medical College have developed and successfully tested in mice an innovative vaccine to treat nicotine addiction.

In the journal Science Translational Medicine, the scientists describe how a single dose of their novel vaccine protects mice, over their lifetime, against nicotine addiction. The vaccine is designed to use the animal’s liver as a factory to continuously produce antibodies that gobble up nicotine the moment it enters the bloodstream, preventing the chemical from reaching the brain and even the heart.

“As far as we can see, the best way to treat chronic nicotine addiction from smoking is to have these Pacman-like antibodies on patrol, clearing the blood as needed before nicotine can have any biological effect,” says the study’s lead investigator, Dr. Ronald G. Crystal , chairman and professor of Genetic Medicine at Weill Cornell Medical College.

“Our vaccine allows the body to make its own monoclonal antibodies against nicotine, and in that way, develop a workable immunity,” Dr. Crystal says.

Previously tested nicotine vaccines have failed in clinical trials because they all directly deliver nicotine antibodies, which only last a few weeks and require repeated, expensive injections, Dr. Crystal says. Plus, this kind of impractical, passive vaccine has had inconsistent results, perhaps because the dose needed may be different for each person, especially if they start smoking again, he adds.

“While we have only tested mice to date, we are very hopeful that this kind of vaccine strategy can finally help the millions of smokers who have tried to stop, exhausting all the methods on the market today, but find their nicotine addiction to be strong enough to overcome these current approaches,” he says. Studies show that between 70 and 80 percent of smokers who try to quit light up again within six months, Dr. Crystal adds.

About 20 percent of adult Americans smoke, and while it is the 4,000 chemicals within the burning cigarette that causes the health problems associated with smoking — diseases that lead to one out of every five deaths in the U.S. — it is the nicotine within the tobacco that keeps the smoker hooked.

A New Kind of Vaccine

There are, in general, two kinds of vaccines. One is an active vaccine, like those used to protect humans against polio, the mumps, and so on. This kind of vaccine presents a bit of the foreign substance (a piece of virus, for example) to the immune system, which “sees” it and activates a lifetime immune response against the intruder. Since nicotine is a small molecule, it is not recognized by the immune system and cannot be built into an active vaccine.

The second type of vaccine is a passive vaccine, which delivers readymade antibodies to elicit an immune response. For example, the delivery of monoclonal (identically produced) antibodies that bind on to growth factor proteins on breast cancer cells shut down their activity.

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via Cornell
 

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Agent Reduces Autism-Like Behaviors in Mice

Boosts Sociability, Quells Repetitiveness

National Institutes of Health researchers have reversed behaviors in mice resembling two of the three core symptoms of autism spectrum disorders (ASD). An experimental compound, called GRN-529, increased social interactions and lessened repetitive self-grooming behavior in a strain of mice that normally display such autism-like behaviors, the researchers say.

GRN-529 is a member of a class of agents that inhibit activity of a subtype of receptor protein on brain cells for the chemical messenger glutamate, which are being tested in patients with an autism-related syndrome. Although mouse brain findings often don’t translate to humans, the fact that these compounds are already in clinical trials for an overlapping condition strengthens the case for relevance, according to the researchers.

“Our findings suggest a strategy for developing a single treatment that could target multiple diagnostic symptoms,” explained Jacqueline Crawley, Ph.D., of the NIH’s National Institute of Mental Health (NIMH). “Many cases of autism are caused by mutations in genes that control an ongoing process — the formation and maturation of synapses, the connections between neurons. If defects in these connections are not hard-wired, the core symptoms of autism may be treatable with medications.”

Crawley, Jill Silverman, Ph.D., and colleagues at NIMH and Pfizer Worldwide Research and Development, Groton, CT, report on their discovery April 25th, 2012 in the journal Science Translational Medicine.

“These new results in mice support NIMH-funded research in humans to create treatments for the core symptoms of autism,” said NIMH director Thomas R. Insel, M.D. “While autism has been often considered only as a disability in need of rehabilitation, we can now address autism as a disorder responding to biomedical treatments.”

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via Science Daily

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Cerebral palsy drug may be breakthrough

The file is made by Oleg Lukin (myself) e-mail...

The file is made by Oleg Lukin (myself) e-mail: [email protected] (Photo credit: Wikipedia)

“Dramatic improvement in the motor function”

A new treatment helped rabbits born with cerebral palsy to regain near-normal mobility, offering hope of a potential breakthrough in treating humans with the incurable disorder, researchers said Wednesday.

The method, part of the growing field of nanomedicine, worked by delivering an anti-inflammatory drug directly into the damaged parts of the brain via tiny tree-like molecules known as dendrimers.

Baby rabbits treated within six hours of birth showed “dramatic improvement in the motor function” by the fifth day of life, said lead author Sujatha Kannan of the National Institute of Child Health and Human Development Perinatology Research Branch. The study appears in the U.S. journal Science Translational Medicine.

via Ottawa Citizen

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