BreakThrough Digest Medical News |
- Breakthrough cancer-killing treatment avoids harmful side-effects
- Laser light zaps away cocaine addiction
- Scientists identify first potentially effective therapy for human prion disease
| Breakthrough cancer-killing treatment avoids harmful side-effects Posted: 02 Apr 2013 09:00 PM PDT Cancer painfully ends more than 500,000 lives in the United States each year, according to the Centers for Disease Control and Prevention. The scientific crusade against cancer recently achieved a victory under the leadership of University of Missouri Curators’ Professor M. Frederick Hawthorne. Hawthorne’s team has developed a new form of radiation therapy that successfully put cancer into remission in mice. This innovative treatment produced none of the harmful side-effects of conventional chemo and radiation cancer therapies. Clinical trials in humans could begin soon after Hawthorne secures funding.
“Since the 1930s, scientists have sought success with a cancer treatment known as boron neutron capture therapy (BNCT),” said Hawthorne, a recent winner of the National Medal of Science awarded by President Obama in the White House. “Our team at MU’s International Institute of Nano and Molecular Medicine finally found the way to make BNCT work by taking advantage of a cancer cell’s biology with nanochemistry.” Cancer cells grow faster than normal cells and in the process absorb more materials than normal cells. Hawthorne’s team took advantage of that fact by getting cancer cells to take in and store a boron chemical designed by Hawthorne. When those boron-infused cancer cells were exposed to neutrons, a subatomic particle, the boron atom shattered and selectively tore apart the cancer cells, sparing neighboring healthy cells. The physical properties of boron made Hawthorne’s technique possible. A particular form of boron will split when it captures a neutron and release lithium, helium and energy. Like pool balls careening around a billiards table, the helium and lithium atoms penetrate the cancer cell and destroy it from the inside without harming the surrounding tissues. “A wide variety of cancers can be attacked with our BNCT technique,” Hawthorne said. “The technique worked excellently in mice. We are ready to move on to trials in larger animals, then people. However, before we can start treating humans, we will need to build suitable equipment and facilities. When it is built, MU will have the first radiation therapy of this kind in the world.” Hawthorne believes that his discovery was possible only at the University of Missouri because MU has three features that separate it from other universities in the nation, the reason Hawthorne came to MU from the University of California, Los Angeles in 2006. “First, it is an example of a small number of universities in the United States with a large number of science and engineering disciplines on the same campus,” said Hawthorne. “Second, the largest university research nuclear reactor is located at MU. Finally, it has strong, collegial biomedicine departments. This combination is unique.” ### The Proceedings of the National Academy of Sciences (PNAS) recently published the study, entitled “Boron neutron capture therapy demonstrated in mice bearing EMT 6 tumors following selective delivery of boron by rationally designed liposomes.” http://www.pnas.org/content/early/2013/03/27/1303437110 Contact: Tim Wall |
| Laser light zaps away cocaine addiction Posted: 02 Apr 2013 09:00 PM PDT By stimulating one part of the brain with laser light, researchers at the National Institutes of Health (NIH) and the Ernest Gallo Clinic and Research Center at UC San Francisco (UCSF) have shown that they can wipe away addictive behavior in rats ? or conversely turn non-addicted rats into compulsive cocaine seekers.
“When we turn on a laser light in the prelimbic region of the prefrontal cortex, the compulsive cocaine seeking is gone,” said Antonello Bonci, MD, scientific director of the intramural research program at the NIH’s National Institute of Drug Abuse (NIDA), where the work was done. Bonci is also an adjunct professor of neurology at UCSF and an adjunct professor at Johns Hopkins University. Described this week in the journal Nature, the new study demonstrates the central role the prefrontal cortex plays in compulsive cocaine addiction. It also suggests a new therapy that could be tested immediately in humans, Bonci said. Any new human therapy would not be based on using lasers, but would most likely rely on electromagnetic stimulation outside the scalp, in particular a technique called transcranial magnetic stimulation (TMS). Clinical trials are now being designed to test whether this approach works, Bonci added. The High Cost of Cocaine Abuse Cocaine abuse is a major public health problem in the United States today, and it places a heavy toll on society in terms of lost job productivity, lost earnings, cocaine-related crime, incarcerations, investigations, and treatment and prevention programs. The human toll is even greater, with an estimated 1.4 million Americans addicted to the drug. It is frequently the cause of emergency room visits ? 482,188 in 2008 alone ? and it is a top cause of heart attacks and strokes for people under 35. One of the hallmarks of cocaine addiction is compulsive drug taking ? the loss of ability to refrain from taking the drug even if it’s destroying one’s life. What makes the new work so promising, said Bonci, is that Billy Chen of NIDA, the lead author of the study, and his colleagues were working with an animal model that mimics this sort of compulsive cocaine addiction. The animals, like human addicts, are more likely to make bad decisions and take cocaine even when they are conditioned to expect self-harm associated with it. Electrophysiological studies involving these rats have shown that they have extremely low activity in the prefrontal cortex ? a brain region fundamental for impulse control, decision making and behavioral flexibility. Similar studies that imaged the brains of humans have shown the same pattern of low activity in this region in people who are compulsively addicted to cocaine. Altering Brain Activity with a Laser To test whether altering the activity in this brain region could impact addiction, Chen and his colleagues employed a technique called optogenetics to shut the activity on and off using a laser. First they took light-sensitive proteins called rhodopsins and used genetic engineering to insert them into neurons in the rat’s prefrontal cortex. Activating this region with a laser tuned to the rhodopsins turned the nerve cells on and off. Turning on these cells wiped out the compulsive behavior, while switching them off turned the non-addicted ones into addicted, researchers found. What’s exciting, said Bonci, is that there is a way to induce a similar activation of the prelimbic cortex in people through a technique called transcranial magnetic stimulation (TMS), which applies an external electromagnetic field to the brain and has been used as a treatment for symptoms of depression. Bonci and his colleagues plan to begin clinical trials at NIH in which they will use this technique a few sessions a week to stimulate the prefrontal cortex in people who are addicted to cocaine and see if they can restore activity to that part of the brain and help them avoid taking the drug. ### The article, “Rescuing cocaine-induced prefrontal cortex hypoactivity prevents compulsive cocaine seeking” is authored by Billy T. Chen, Hau-Jie Yau, Christina Hatch, Ikue Kusumoto-Yoshida, Saemi L. Cho, F. Woodward Hopf and Antonello Bonci. It is published online by the journal Nature on April 3, 2013. After that date, the article can be accessed. In addition to UCSF, the authors of this study are affiliated with the National Institute on Drug Abuse, the Ernest Gallo Clinic and Research Center and the Solomon H. Snyder Neuroscience Institute, Johns Hopkins School of Medicine. This work was funded by the National Institute on Drug Abuse. UCSF is a leading university dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care. Follow UCSF UCSF.edu | Facebook.com/ucsf | Twitter.com/ucsf | YouTube.com/ucsf Contact: Jason Socrates Bardi |
| Scientists identify first potentially effective therapy for human prion disease Posted: 02 Apr 2013 09:00 PM PDT Human diseases caused by misfolded proteins known as prions are some of most rare yet terrifying on the planet?incurable with disturbing symptoms that include dementia, personality shifts, hallucinations and coordination problems. The most well-known of these is Creutzfeldt-Jakob disease, which can be described as the naturally occurring human equivalent of mad cow disease.
Now, scientists from the Florida campus of The Scripps Research Institute (TSRI) have for the first time identified a pair of drugs already approved for human use that show anti-prion activity and, for one of them, great promise in treating these universally fatal disorders. The study, led by TSRI Professor Corinne Lasmézas and performed in collaboration with TSRI Professor Emeritus Charles Weissmann and Director of Lead Identification Peter Hodder, was published this week online ahead of print by the journal Proceedings of the National Academy of Sciences. The new study used an innovative high-throughput screening technique to uncover compounds that decrease the amount of the normal form of the prion protein (PrP, which becomes distorted by the disease) at the cell surface. The scientists found two compounds that reduced PrP on cell surfaces by approximately 70 percent in the screening and follow up tests. The two compounds are already marketed as the drugs tacrolimus and astemizole. Tacrolimus is an immune suppressant widely used in organ transplantation. Tacrolimus could prove problematic as an anti-prion drug, however, because of issues including possible neurotoxicity. However, astemizole is an antihistamine that has potential for use as an anti-prion drug. While withdrawn voluntarily from the U.S. over-the-counter market in 1999 because of rare cardiac arrhythmias when used in high doses, it has been available in generic form in more than 30 countries and has a well-established safety profile. Astemizole not only crosses the blood-brain barrier, but works effectively at a relatively low concentration. Lasmézas noted that astemizole appears to stimulate autophagy, the process by which cells eliminate unwanted components. “Autophagy is involved in several protein misfolding neurodegenerative diseases such as Alzheimer’s, Parkinson’s and Huntington’s diseases,” she said. “So future studies on the mode of action of astemizole may uncover potentially new therapeutic targets for prion diseases and similar disorders.” The study noted that eliminating cell surface PrP expression could also be a potentially new approach to treat Alzheimer’s disease, which is characterized by the build-up of amyloid ? plaque in the brain. PrP is a cell surface receptor for A? peptides and helps mediate a number of critical deleterious processes in animal models of the disease. ### The first author of the study, “Unique Drug Screening Approach for Prion Diseases Identifies Tacrolimus and Astemizole as Antiprion Agents,” is Yervand Eduard Karapetyan of The Scripps Research Institute. Other authors include Gian Franco Sferrazza, Minghai Zhou, Gregory Ottenberg, Timothy Spicer, Peter Chase, Mohammad Fallahi, Peter Hodder and Charles Weissmann of The Scripps Research Institute. For more information on the study, see http://www.pnas.org/content/early/2013/03/29/1303510110.abstract The research was supported by The Scripps Research Institute, the Alafi Foundation and the National Institutes of Health (Grant MH084512). Contact: Eric Sauter |
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