Dipali Pathak
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HOUSTON -- (Oct. 5, 2009) -- A cocaine vaccine that recruits the immune system to help block the drug's euphoric effects proved effective in 38 percent of subjects who received the vaccine, said a Baylor College of Medicine researcher who led the study.

Q&A with Dr. Kosten

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Text-only Q&A

A consortium of researchers began the work when principal investigator Dr. Thomas R. Kosten, a professor at BCM, was on faculty at Yale University School of Medicine. Kosten and his team evaluated the safety and effectiveness of a novel cocaine vaccine that has been more than 15 years in development. The report appears in the current issue of Archives of General Psychiatry.

Plans to improve cocaine vaccine

"The concept works," said Kosten, "There are lots of ways to engineer it after that to make it work better."

He plans to continue work to improve the vaccine and find better ways to bolster the immune system against the effects of cocaine.

Kosten holds the Jay H. Waggoner Endowed Chair in the Menninger Department of Psychiatry and Behavioral Sciences at BCM. He is also the research director of the Veterans Affairs National Substance Use Disorders Quality Enhancement Research Initiative based at the Michael E. DeBakey Veterans Affairs Medical Center in Houston.

This study took place in one center, the Veterans Affairs Connecticut Healthcare System. Plans for a study of the vaccine in many sites are now under way.

Promising step

"The results of this study represent a promising step toward an effective medical treatment for cocaine addiction," said Dr. Nora Volkow, director of the National Institute on Drug Abuse. "Provided that larger follow-up studies confirm its safety and efficacy, this vaccine would offer a valuable new approach to treating cocaine addiction, for which no FDA-approved medication is currently available."

Kosten is quick to note that the vaccine is not a panacea, but the result shows that a vaccine can work in addictive disease, he said.

"The vaccine provokes the body to make antibodies. These antibodies bind to the cocaine, preventing it from leaving the bloodstream," said Kosten.

The cocaine can be excreted in the liver or kidneys. An enzyme in the blood, cholinesterase, breaks down the cocaine. The fact that this enzyme continually breaks the drug down makes cocaine a better target for vaccines than other addictive drugs.

Effectiveness depends on level of antibody

In the study, 94 subjects who were on methadone were randomized to receive either the vaccine or an inactive medicine, a placebo. Neither they nor the physicians knew who received the vaccine until the study was over. Most subjects smoked crack cocaine. Over 12 weeks, the subject received five injections of either the vaccine or the placebo.

The vaccine's effect depended on the level of antibody achieved. Those who reach high levels of antibodies are more likely to be able to stay cocaine-free.

"That's the biggest problem with this vaccine. It is first generation and it does not create antibodies in everybody," said Kosten. "Twenty-five percent of the people who get the vaccine do not make much antibody response."

Relapse prevention medication

The vaccine can act as a preventive to relapse for those who want to stop taking the drug, Kosten said. It does not completely prevent cocaine cravings, but when the effect of the drug is blocked by the vaccine, people's cravings will diminish.

"This is a relapse prevention medication. If you take cocaine, you won't feel anything," he said.

Others who took part in this research include Drs. Bridget A. Martell and James Poling and registered nurse Ellen Mitchell of Yale University School of Medicine and the Veterans Affairs Connecticut Hospital; and Drs. Frank M. Orson, Roger D. Rossen and Tracie Gardner of Baylor College of Medicine and the Michael E. DeBakey Veterans Affairs Medical Center in Houston.

Funding for this study came from the National Institute of Drug Abuse, the Veterans Affairs Mental Illness Research, Education and Clinic Center in New England, the Veterans Affairs Office of Research and Development/Cooperative Studies Program Career Development Award. Celtic Pharmaceuticals provided vaccine and paid travel fees for consultative services as well as providing a small amount of administrative funds for design and conduct of the study.

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HOUSTON -- (October 2, 2009) -- Finding a treatment for a deadly type of skin cancer could be closer now that Merkel cells are found to originate from the skin, say researchers from Baylor College of Medicine in Houston and Case Western Reserve University School of Medicine in Cleveland, in a report that appears in the journal Developmental Biology.

In hairy skin, Merkel cell-neurite complexes cluster together and form touch domes. As shown in schematic, a sensory neuron (purple) contacts a cluster of mouse Merkel cells (green) in the skin at the epidermal-dermal interface.

"Our previous study showed direct evidence that Merkel cells are essential for detecting light touch," said Dr. Ellen Lumpkin, assistant professor of neuroscience, molecular physiology and biophysics and molecular and human genetics at BCM. "Our latest finding shows us more characteristics of these cells that will have implications in not only neuroscience research, but also dermatology since Merkel cells give rise to Merkel cell carcinoma."

Knowledge of origin helpful

Since the cell's first description in 1875, researchers have speculated whether they derived from skin cells or neural crest cells. Neural crest cells form, among other structures, most of the peripheral nervous system.

"Merkel cells have characteristics that make them more akin to neural crest cells, such as appearance and proteins they express," said Dr. Stephen Maricich, assistant professor of pediatrics, neurosciences and otolaryngology at CWRU SOM. "Not knowing exactly how they developed made treating Merkel cell carcinoma and other skin problems difficult." Merkel cells may be involved in other skin conditions such as psoriasis, added Maricich.

Knocking out Atho1

Mice were injected with FM1-43, a fluorescent dye which labels sensory cells and neurons, 24 hr before imaging the touch domes. In wild-type mice (A), both the Merkel cells (triangle arrow heads) and the sensory nerve fiber (arrows) are visible. In the mice where Atoh1 has been deleted (B), no cells resembling Merkel cells are seen, confirming these mice lack Merkel cells. The nerve fiber is present and hyper-innervates the vacant touch dome. These data support epidermal origin of Merkel cells.

Using genetically-engineered mouse lines, researchers were able to delete Atoh 1, a gene essential to the formation of Merkel cells. When this was done in the neural crest, Merkel cells still developed. However, when this same process was completed in the skin, Merkel cells did not develop.

"Knocking out Atoh 1 in the neural crest line caused other problems despite Merkel cells being present. However, when Atoh 1 was knocked out in skin cells, only Merkel cells were missing with no other issues," said Maricich, who is lead author on the study. "This showed us that we had specifically targeted the Merkel cells and that Atoh 1 in skin cells was necessary to their development."

Fate mapping

Immunostaining using Merkel-cell specific markers confirms Merkel cell loss in Atoh1 conditional knockout mice. As seen in the top panel, wild-type touch domes contain Merkel cells (Keratin8, green) and sensory nerve fibers (Neurofilament-200, red). In the bottom panel, Atoh1 conditional knockout touch domes have no Keratin-8 staining, confirming Merkel cell absence. However, as seen in the FM images, the nerve (red) hyper-innervates the vacant touch dome.

Researchers also fate mapped the cells, which supported their initial findings. Fate mapping is a technique used to trace the developmental fate of an embryo, showing which tissues the cells in each region will give rise to.

"The techniques used in this study will help neuroscientists to further explore the function of Merkel cells, including the behavioral consequences when only Merkel cells have been deleted," said Lumpkin, a study co-author.

Another aspect of future research, said Lumpkin, is understanding how these touch receptors affect the development of the brain.

Funding for this study came from the National Institute of Neurological Disorders and Stroke and the National Institute of Arthritis and Musculoskeletal and Skin Diseases.

Other researchers who contributed to this study include Dr. George R. Miesegaes, department of molecular and human genetics at BCM, now with the U.S. Food and Drug Administration, Center for Drug Evaluation and Research; and Kristin M. Morrison, department of pediatrics, Case Western Reserve University.

For more information on basic science research at Baylor College of Medicine, please go to www.bcm.edu/fromthelab or www.bcm.edu/news.

Images courtesy Aislyn Nelson and Dr. Ellen Lumpkin.

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HOUSTON -- (September 30, 2009) -- In the seemingly simple world of the social amoeba, some cheat, giving advantage to their genetic kin. Why, then, do they not take over the population?

One possibility, said collaborating researchers from Baylor College of Medicine and Rice University, are mutations that confer the ability to resist cheaters. They describe this population in a report that goes online today in the journal Nature.

"These resistant strains are 'noble' in that they do not take advantage of the other strains," said Anupama Khare, a graduate student in the laboratory of Dr. Gad Shaulsky at BCM and the paper's first author. "In fact, they even reduce the cheater's ability to cheat such strains."

The paper is the latest chapter in the story of the Dictyostelium discoideum or social amoeba that is being unraveled in the laboratories of Shaulsky, professor of molecular and human genetics at BCM, Dr. Adam Kuspa, chair of biochemistry and molecular biology at BCM and Dr. Joan E. Strassmann and Dr. David C. Queller, professors in the department of ecology and evolutionary biology at Rice University.

Stalks and spores

Social amoebae live as single-cell organisms in normal times. When starved, they form multi-cellular organisms made up of stalks and spores. At one point in this process, some of the cells "sacrifice" themselves and become the dead stalks that support a body of spores, made up of living cells that keep the population alive. This population can be genetically diverse, and a roughly equal proportion of cells from the different gene pools sacrifice themselves to become stalks. That means that the different gene types survive in equal proportions.

Yet some amoeba "cheat" and as a result, more of that particular genotype survives. If this strategy always worked, these "cheaters" would take over the population.

Cheater resistant

To test their hypothesis that some amoebas are cheater resistant, the researchers mixed a population of mutated cells with a cheater strain and allowed them to develop into stalks and spores as chimeras. They thought that the cheater cells would exploit most of the cells in the mutant population, and that a high proportion of any cells left would be resistant to cheating. After several generations, their hypothesis proved true. Further studies showed that these "noble" social amoebae not only resisted the cheaters, they also did not themselves cheat on other amoebae.

"In this study Anu has demonstrated so clearly and cleanly such a response to cheaters at the molecular level. It is also very interesting that these resisters are noble, in the sense that they themselves do not exploit their ancestor," said Strassmann.

"The active cheating in social amobae is more similar to animal sociality, and is therefore a good model system for exploring the complex evolutionary dynamics of genes affecting cooperation, cheating and cheater-resistance," the authors wrote.

"The ones we identified don't abolish cheating completely," said Khare.

"Think of them as the firebreaks that prevent the flames from spreading," said Shaulsky. "Or they are like the people resistant or vaccinated against the flu that prevent it from spreading."

Lorenzo Santorelli of both BCM and Rice also took part in this work.

Funding for this research came from the National Science Foundation and the Cullen Foundation.

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HOUSTON -- (September 24, 2009) -- Early-stage intervention in prostate cancer is the best approach to treatment of the disease, said a urologist at Baylor College of Medicine.

"Before the PSA screening era, one out of every three prostate cancer patients who underwent surgery was too late for intervention," said Dr. Dov Kadmon, professor of urology at BCM and co-leader of the prostate cancer program in the NCI-designated Dan L. Duncan Cancer Center at BCM. "This, and other significant advancements, have given physicians a better understanding of the disease and reaffirm the importance of treating prostate cancer early."

Better, more advanced treatments

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Kadmon said physicians now have better, more advanced treatments and approaches to managing treatment-related side effects. They have been able to prolong survival and reduce the incidences of prostate cancer-related mortality and morbidity.

Approximately 190,000 new cases of prostate cancer are expected to be diagnosed this year, Kadmon said, and 27,000 will die from the disease. Prostate cancer, when caught in the early stages (when the cancer has been found only in the prostate gland) is highly treatable and curable, Kadmon said.

PSA early indicator

The introduction of the prostate-specific antigen test about 15 years ago has strongly influenced the ability to catch cancer early, Kadmon said.

"PSA is a protein produced by normal and cancerous prostate cells," said Kadmon. "PSA blood levels are elevated when produced by prostate cancer cells."

Depending on a man's age, there are recommended blood levels that may indicate the need for a biopsy and further treatment.

Standard forms of early prostate cancer treatment include surgery (removal of the prostate gland) and radiation therapy.

"The doctor and patient should jointly decide whether to seek treatment or be watched closely," said Kamdon. "We have a lot more data available today to help them make those decisions."

Patients also have the option of minimally invasive surgeries that reduce time needed for recovery, Kadmon said.

Screening recommendations

Beginning at age 50, it is recommended that men have a PSA or screening test every year. Men with a family history of prostate cancer and African American men should begin yearly screenings at age 40.

Kadmon said men should continue prostate cancer screenings and consider treatment if necessary into their late 70s.

"Physicians should continue pursuing long-term goals of curing prostate cancer and reducing morbidity and mortality," said Kadmon. "There should continue to be an emphasis on the importance of early treatment for the disease."

September is Prostate Cancer Awareness Month.

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HOUSTON -- (September 24, 2009) -- Telling a child that a parent has cancer is often one of the toughest hurdles of a cancer diagnosis. When facing this situation, it's important not to hide information from children, said an expert at Baylor College of Medicine.

"Kids have good intuition and know when something is wrong. Hiding this information from them may make them think they did something wrong or it's their fault," said Dr. Leng Bang, assistant professor of psychiatry and behavioral sciences at BCM.

How to approach cancer discussion

The age of the child determines how to approach the subject, said Bang.

"With very young kids, I would recommend saying that the parent is sick and that they are going through treatment. With older kids, you can talk to them about cancer and how the parent can get better," said Bang.

It is OK to use the word "cancer" and even show them where the cancer is in the body, he said. Children often do better when they have the appropriate information. If they don't, they may make up their own explanations about why mom or dad has cancer, which can be more frightening than the truth. Reassure children that their behavior or their thinking did not cause the cancer. Let children know that they can not "catch" cancer.

Talk about treatment plan

It's important not to give too much information, but also to communicate the plan, he said. Talk about what the treatment will be like and that there's a possibility that the parent's hair might fall out so children will anticipate what the parent might go through.

Knowing these possible outcomes will help children adjust to the changes they see with their parents. Have children participate in the treatment process if possible by giving them age-appropriate tasks, such as getting a glass of water or crossing out number of treatments left in a series of chemotherapy.

"One important thing is to be sure that the parent who has been diagnosed with cancer is coping well, because children will reflect their attitude. If the parent is positive and hopeful, the child will also be," said Bang.

Watch out for signs of anxiety

Bang also suggests looking for signs that the child is having trouble coping with the situation. If the child is afraid of going to school and leaving the parent alone, or reflecting symptoms similar to what the parent is going through, it may be time to seek help from a mental health professional.

"It's important to keep an eye out for signs of anxiety and depression," he said.

It's not necessary to talk about death and dying unless it's a serious possibility, Bang advised.

"Younger kids don't know that death is permanent and may not understand, but older children may recognize this," said Bang. "It's important to sit with your kids and listen to their worries and their fears."

Encourage children to express their feelings, even uncomfortable ones, he said. And reassure children that someone will always be there to take care of them. Continue to maintain open communication with children as much as possible.

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