Alho tem atividade antimicrobiana semelhante à dos antibióticos

Amostras de alho testadas em laboratório mostraram que o alimento é tão eficiente em combater infecções quanto o antibiótico amoxicilina.

Tipos de alho

A utilização do alho nos alimentos e como medicamento se perde nos tempos. Segundo algumas evidências, seu emprego em várias culturas começou há pelo menos seis mil anos.

Hoje se conhecem cerca de 600 espécies de alho e o gênero Allium é frequentemente referência em estudos e utilizado em medicina devido às propriedades antimicrobiana e antiviral, entre outras.

Com base no Allium sativum, comumente consumido no Brasil, e noAllium tuberosum, o conhecido alho nirá, que compõe a culinária japonesa, o professor de química do Cotil (Colégio Técnico de Campinas), da Unicamp, Paulo César Venancio, pesquisou as atividades antimicrobianas dessas espécies em ratos, comparando-as com o conhecido antibiótico amoxicilina.

Alho contra infecções

Segundo o pesquisador, o trabalho foi orientado na busca de uma alternativa para combater as infecções bacterianas mais incidentes hoje. "Os antibióticos utilizados são específicos para cada tipo de cepa de bactérias, observando-se cada vez mais o aumento de suas resistências a eles. A ideia foi então a de buscar alternativas junto à natureza que possam vir a somar como possibilidades a mais no controle das infecções bacterianas", afirmou.

Para Venancio, o resultado das análises dos extratos revelou a presença de compostos orgânicos e organossulfurados responsáveis pela ação antimicrobiana e provavelmente resultantes da degradação da alicina presente no alho.

Os testes in vitro confirmaram a ação antimicrobiana do A. sativum, mas surpreendentemente mostraram que esse efeito não se manifesta no caso doA. tuberosum.

No modelo utilizado para os ratos, os extratos dos dois alhos mencionados nas diferentes concentrações utilizadas foram capazes de diminuir de maneira eficaz e comparável à amoxicilina a infecção estafilocócica.

Alho como antibiótico

Para chegar à escolha do alho, Venancio pesquisou inicialmente quais as plantas que apresentavam melhor eficácia contra infecção, mais especificamente no combate aos Staplylococcus aureus, frequentemente isolado na pele, glândulas cutâneas e em mucosas.

Ao justificar a seleção da bactéria, o pesquisador esclarece que ela, que faz parte da microbiota humana, ao encontrar condições favoráveis, pode entrar na corrente sanguínea e se alojar em vários órgãos ou tecidos e causar efeitos devastadores. Esta bactéria é uma das maiores responsáveis pelas infecções hospitalares.

Moveu-o, ainda, o fato de a Anvisa ter lançado em 2010 uma relação de plantas medicinais em que o alho, tradicionalmente considerado antisséptico, tem esse efeito destacado.

O pesquisador enfatiza que o estudo teve por objetivo principal avaliar in vivoa atividade antimicrobiana de extratos dos dois alhos mencionados sobre a infecção estafilocócica em ratos. Paralelamente, determinou as mesmas atividades in vitro, ou seja, com bactérias cultivadas em laboratório. A comparação dos resultados obtidos nos dois estudos permitiu aventar eventuais efeitos fisiológicos sobre os animais.

Mais ainda: para estabelecer parâmetros com outros trabalhos desenvolvidos, Venancio determinou a composição química dos extratos, ou seja, a qualidade e a quantidade de substâncias neles presentes, o que possibilitaria confirmar aquelas responsáveis pelo princípio ativo.

Suco de alho

Entusiasmado com os efeitos benéficos do alho, o autor enfatiza que qualquer pessoa pode fazer um extrato de alho.

Basta pegar um dente de alho que pesa cerca de 500mg (meio grama), triturá-lo, colocar a massa macerada em meia xícara de água e deixar por 20 minutos.

Segundo ele, ao tomar o suco nas refeições, a pessoa está ingerindo um excelente antimicrobiano.

"Fizemos um estudo que pudesse resultar em algo útil e com resultados práticos que podem prontamente ser utilizados pela população", concluiu.

Receita de alho

Paulo Cesar Venancio defende que, se o médico não desejar prescrever apenas o alho nos casos de infecção, pode associá-lo ao antimicrobiano de forma a alcançar sinergismo. Para ele, a idéia do uso simultâneo é melhorar a ação dos antimicrobianos e quem sabe futuramente recuperar antibióticos que não fazem mais efeito.

A análise química da composição dos extratos se justifica porque o alho é constituído por muitas substâncias, daí a importância de determinar quais estavam presentes nos extratos. Porque, afirma Venâncio, "hoje importa na medicina conhecer isoladamente os compostos presentes para poder isolá-los e identificar os responsáveis pelos princípios ativos". Ele, entretanto, esclarece que seu objetivo foi o de apenas identificar os compostos para poder estabelecer uma comparação com os estudos já existentes.

Diz ele que esse parâmetro precisava ser dado à comunidade científica para que pudessem ser comparadas as composições dos alhos aqui cultivados com os já estudados. Os estudos prévios por ele realizados mostram que os componentes mais ativos são os sulfurados, compostos orgânicos à base de enxofre, provavelmente resultantes da degradação da alicina. O estudo permitiu constatar que esses compostos também são preponderantes nos alhos utilizados.

A ação do alho japonês é pouco conhecida e existem poucos estudos sobre ele. Segundo o autor, o que diferencia seu trabalho dos já existentes é a escolha das bactérias Staplylococcus aureus, as maiores responsáveis pelas infecções hospitalares.

Células do coração e ouvido são acionadas por luz infravermelha

Movidos a luz

Cientistas da Universidade de Utah, nos Estados Unidos, descobriram que a luz infravermelha, que não é vista pelo olho humano, faz as células cardíacas se contraírem e as células do ouvido interno enviarem sinais ao cérebro.

A descoberta poderá ser importante para melhorar a qualidade de implantes cocleares para surdez e permitir a criação de dispositivos para restaurar a visão, manter o equilíbrio e tratar perturbações do movimento, como o Mal de Parkinson.

"Poderemos conversar com o cérebro com impulsos ópticos infravermelhos, em vez de pulsos elétricos," que hoje são usados nos implantes cocleares, diz o Dr. Richard Rabbitt, que coordenou as pesquisas, feitas em animais de laboratório.

Luz para o coração

O estudo também abre a possibilidade de desenvolver marca-passos cardíacos que usem sinais ópticos, em vez de sinais elétricos, para estimular as células do coração, embora o pesquisador afirme que, como os marca-passos eletrônicos funcionam bem "eu não vejo um mercado para um marca-passo óptico na atualidade."

O significado científico da pesquisa está na descoberta de que os sinais ópticos - pulsos curtos de uma onda invisível de um laser infravermelho, transmitido através de uma fibra óptica - podem ativar as células do coração e as células do ouvido interno relacionadas ao equilíbrio e à audição.

Além disso, a pesquisa mostrou que a luz infravermelha ativa as células do coração, chamadas cardiomiócitos, disparando o movimento de íons de cálcio para dentro e para fora das mitocôndrias, as organelas das células que transformam o açúcar em energia utilizável.

Parece ser esse o mesmo processo que ocorre quando a luz infravermelha estimula as células do ouvido interno.

Luz infravermelha

A luz infravermelha pode ser sentida como calor, levantando a possibilidade adicional de que as células do coração e dos ouvidos possam ser ativadas por calor, em lugar da própria radiação infravermelha.

Os pulsos de luz infravermelha de baixa potência usados no estudo foram gerados por um diodo laser, semelhante ao utilizado nos apontadores usados em apresentações - só que, neste caso, o diodo emite uma luz visível.

As células do coração usadas no estudo foram retiradas de camundongos recém-nascidos. Esses cardiomiócitos são responsáveis por fazer o coração bater.

As células do ouvido interno são células ciliadas, e foram retiradas do órgão do ouvido interno que detecta o movimento da cabeça. As células ciliadas foram retiradas de um tipo de peixe que os cientistas usam como um modelo para estudo dos ouvidos humanos.

Implantes multifrequenciais

As células ciliadas do ouvido interno, por exemplo, transformam as vibrações mecânicas do som em sinais que são enviados ao cérebro por meio de células nervosas que se ligam a elas.

Agora os cientistas conseguiram obter os mesmos impulsos acionando as células com luz.

Os implantes cocleares atuais convertem o som em sinais elétricos, que normalmente são transmitidos a oito eletrodos na cóclea, uma parte do ouvido interno, onde as vibrações sonoras são convertidas em impulsos nervosos enviados ao cérebro.

Oito eletrodos podem transmitir apenas oito frequências de som, enquanto um adulto saudável pode ouvir mais de 3.000 frequências diferentes.

Com a estimulação óptica, os eletrodos podem ser dispensados, e um futuro equipamento baseado nesta descoberta poderia enviar centenas ou milhares de frequências.

Descoberta de cientistas brasileiros oferece tratamento para Chagas

'Trypanosoma cruzi' causa mutações genéticas nas células do hospedeiro. Teoricamente, transplante de medula óssea evita as lesões no coração.

Cientistas brasileiros elaboraram um novo tipo de tratamento para a doença de Chagas. A possível cura é baseada em mais de 30 anos de estudos que levaram à compreensão de como o Trypanosoma cruzi – protozoário que causa a doença – interage com o corpo do hospedeiro.

As pessoas infectadas pela doença de Chagas sofrem lesões no coração que levam à morte. Antônio Teixeira, pesquisador da Universidade de Brasília (UnB), descobriu que as lesões não são necessariamente causadas pelo T. cruzi, mas pelo próprio sistema imunológico do hospedeiro – processo conhecido como autoimunidade.

Ao longo de anos pesquisas, os cientistas descobriram que o microorganismo causa mutações genéticas nas células do hospedeiro. Uma vez que isso acontece, o sistema imunológico passa a produzir linfócitos – células de defesa – defeituosos, que atacam o coração. Desta forma, exterminar o protozoário não é suficiente para eliminar a doença.

O estudo mais recente foi feito com galinhas, que são imunes à infecção pelo T. cruzi. Com a mutação genética induzida, desenvolveram problemas cardíacos bastante semelhantes aos causados pela doença de Chagas, comprovando a hipótese. Essa pesquisa foi publicada pela revista científica “PLoS Neglected Tropical Diseases”.

Com a descoberta, há um novo tratamento possível para a doença de Chagas. Os linfócitos são produzidos na medula óssea. Portanto, Teixeira sugere que, matando os linfócitos e fazendo um transplante de medula óssea – tratamentos já existentes –, seja possível prevenir a doença. Se o coração já estiver danificado, o transplante também é uma solução.

“A função da ciência é oferecer soluções. Agora cabe à medicina utilizá-las”, afirma Teixeira, ao G1. Ele ressalta que, uma vez que a doença ataca o coração, a morte é uma questão de tempo e que, por isso, vale a pena pôr o tratamento em prática.

Trajetória

Teixeira dedica o resultado de anos de pesquisas a um agricultor que morreu aos 42 anos, pai de sete filhos, cujas iniciais eram J.E.S.. “Eu era assistente na clínica de cardiologia e ele foi meu paciente. Seis meses depois, eu estava na patologia, chegou o corpo dele e eu fui fazer o exame. Ele estava com o coração grande (inchado), mas não tinha Trypanosoma cruzi”, lembra-se. Desde então, o cientista vinha tentando compreender como se davam as lesões, uma vez que não eram necessariamente causadas pelo protozoário.

Ele agradece ainda a todos os pesquisadores que se dedicaram ao tema em pesquisas de pós-graduação, não apenas na UnB. “É uma história de construção coletiva de conhecimento científico”, define.

Cancer Turns out to Be a P53 Protein Aggregation Disease

ScienceDaily (Mar. 29, 2011) — Protein aggregation, generally associated with Alzheimer's and mad cow disease, turns out to play a significant role in cancer. In a paper published in Nature Chemical Biology, Frederic Rousseau and Joost Schymkowitz of VIB, K.U.Leuven and Vrije Universiteit Brussel describe that certain mutations of p53, an important tumor suppressor, cause the protein to misfold in a way that the proteins start to aggregate. This not only disrupts the protective function of normal p53, but of other related proteins as well.

p53 is crucial for protection against cancer, but mutation transforms this important tumor suppressor into a potent oncogene. This illustration by Jie Xu is an adaptation of 'Starry Night' by Vincent Van Gogh and shows depicts the catastrophic events following the self-assembly of p53 family members into cellular inclusions.

p53 plays a central role in protection against cancer

In the study, the focus was on the p53 protein which plays a key role in protecting the body against cancer. If p53 works normally, it controls cell division. If p53 control ceases -- e.g. when there is a mutation in the protein -- the cells start to divide in an uncontrolled manner and this may result in a tumor. Mutations in p53 are observed in about half of cancer cases, making the protein an important target in the development of new cancer therapies.

Mutated p53 aggregates

"We have revealed a new mechanism for the action of mutant p53," Joost Schymkowitz and Frederic Rousseau of VIB, Vrije Universiteit Brussel and K.U. Leuven say. "Mutations in p53 cause the protein to lose its protective function. The proteins change in shape, hook into each other and begin to aggregate. The active p53 disappears from the cell and can no longer carry out its control function properly." The mechanism has been encountered in about one third of p53 mutations.

Complete switch of character

Moreover, the mutations cause p53 to assume a completely different character. From being a protective factor, the mutated p53 changes into a substance which in fact speeds up tumor growth. It seems to form aggregates with control substances (p63 and p73) in the cell, causing them to lose their function as well.

Other proteins underlying cancer and Alzheimer

Even though the underlying principle -- protein aggregation -- occurs similarly in particular cancers, Alzheimer and systemic amyloidosis, the diseases are otherwise totally unconnected with each other. In cancer, the clustering of p53 protein leads to uncontrolled cell growth. In Alzheimer, clustering of the beta-amyloid protein causes brain cells to die off.

Pioneering Treatment Could Help People With Severe Depression

ScienceDaily (Mar. 29, 2011) — Pioneering neurosurgical treatment, which very accurately targets brain networks involved in depression, could help people who suffer with severe and intractable depression.

Sagittal MRI scan of the brain showing the position of one of the deep brain stimulation (DBS) leads and one of the guide tubes for anterior cingulotomy (GTAC). Scan taken during surgery. [A]= front of brain.

The research led by Dr Andrea Malizia, Consultant Senior Lecturer in the School of Social and Community Medicine at the University of Bristol and Mr Nikunj Patel, Senior Clinical Lecturer in the Department of Neurosurgery at North Bristol NHS Trust, are pioneering a number of treatments including experimental antidepressants, deep brain stimulation (DBS) and stereotactic neurosurgery.

The patient, whose illness had stopped responding to conventional treatments, was offered DBS in the first trial in the world that stimulates two different brain networks that are involved in depression. DBS in this case provided some temporary response but was not sufficient to make her well. She is now well following further advanced stereotactic neurosurgery carried out in early 2010.

Deep brain stimulation consists of inserting thin wires in the brain that are connected to a 'pacemaker'. The effects are to inhibit and stimulate brain circuits that re specific to the condition being treated. The current DBS trial targets different circuits involved in depression. These monitor the regulation of emotion, oversee the integration of emotion with bodily and intellectual function and regulate internal drives.

Some patients do not respond to DBS or are not suitable for it, in which case the option of an 'Anterior Cingulotomy' using implantable guide tubes (GTAC) has been specifically developed in Frenchay and this patient was the first to have it. This operation also modifies circuits that are important in emotion and the academics believe to be overactive in a number of psychiatric disorders. The neurosurgical developments pioneered at Frenchay make the surgery much more accurate and hopefully this will have an impact on increasing efficacy and decreasing side effects.

Dr Malizia said: "Our patients and their families suffer enormously and it is often thought that nothing else can be done. This lady responded temporarily to two of the complex treatments that we initiated in Bristol, but in the end remission has only been achieved by persisting and moving on to the next advanced treatment.

"We are very grateful to our patients and their relatives who, in spite of depression destroying their lives, bravely carry on fighting the illness year after year, and also to the League of Friends at Frenchay hospital who have donated DBS equipment -- their support has been essential in starting this important endeavour."

Depression is an illness that affects about 20 per cent of people at least once in their lifetime. About half the people get well within six months but about ten per cent of sufferers are still unwell after three years. From then on the proportion of people who get well is much reduced with only about one in ten getting better every year.

There are a number of conventional treatments for depression including specific psychotherapies, different antidepressant medicines and electroconvulsive therapy (ECT). Long-term experience has shown that each time a medical treatment does not work, there is a decrease in the probability of the next treatment working of about a third. This means that although 60 per cent of patients respond to the first antidepressant, only about 10 per cent will respond to the fifth. ECT remains the most efficacious short-term treatment but it does not work for everyone, its effects can be short lasting and some people have considerable side effects.

People who experience chronic depression can be very severely disabled: many lose their jobs, are on benefits, have to change home or lose their family. Personal distress is high and about 15 per cent die by suicide.

The Psychopharmacology and Functional Neurosurgery Service in Bristol provides complex treatments for these severely disabled people and aims to understand the brain changes underlying this disorder by using advanced brain imaging techniques and sleep recordings.

Human Virus Linked to Deaths of Endangered Mountain Gorillas; Finding Confirms That Serious Diseases Can Pass to Gorillas from People

ScienceDaily (Mar. 29, 2011) — For the first time, a virus that causes respiratory disease in humans has been linked to the deaths of wild mountain gorillas, reports a team of researchers in the United States and Africa.

The potential for disease transmission between humans and mountain gorillas is of particular concern because over the past 100 years, mountain gorillas have come into increasing contact with humans.

The finding confirms that serious diseases can pass from people to these endangered animals.

The researchers are from the non-profit Mountain Gorilla Veterinary Project; the Wildlife Health Center at the University of California, Davis; the Center for Infection and Immunity at Columbia University; and the Rwanda Development Board.

Their study, which reports the 2009 deaths of two mountain gorilla that were infected with a human virus, was published online by the journalEmerging Infectious Diseases, a publication of the U.S. Centers for Disease Control and Prevention.

"Because there are fewer than 800 living mountain gorillas, each individual is critically important to the survival of their species," said Mike Cranfield, executive director of the Mountain Gorilla Veterinary Project and a UC Davis wildlife veterinarian. "But mountain gorillas are surrounded by people, and this discovery makes it clear that living in protected national parks is not a barrier to human diseases."

Humans and gorillas share approximately 98 percent of their DNA. This close genetic relatedness has led to concerns that gorillas may be susceptible to many of the infectious diseases that affect people.

The potential for disease transmission between humans and mountain gorillas (Gorilla beringei beringei) is of particular concern because over the past 100 years, mountain gorillas have come into increasing contact with humans. In fact, the national parks where the gorillas are protected in Rwanda, Uganda and the Democratic Republic of Congo are surrounded by the densest human populations in continental Africa.

Also, gorilla tourism -- while helping the gorillas survive by funding the national parks that shelter them -- brings thousands of people from local communities and around the world into contact with mountain gorillas annually.

The veterinarians of the Mountain Gorilla Veterinary Project, who monitor the health of the gorillas and treat individuals suffering from life-threatening or human-caused trauma and disease, have observed an increase in the frequency and severity of respiratory disease outbreaks in the mountain gorilla population in recent years.

Infectious disease is the second most common cause of death in mountain gorillas (traumatic injury is the first). "The type of infection we see most frequently is respiratory, which can range from mild colds to severe pneumonia," said co-author Linda Lowenstine, a veterinary pathologist with the UC Davis Mountain Gorilla One Health Program who has studied gorilla diseases for more than 25 years.

The two gorillas described in the new study were members of the Hirwa group living in Rwanda. In 2008 and 2009, this group experienced outbreaks of respiratory disease, with various amounts of coughing, eye and nose discharge, and lethargy. In the 2009 outbreak, the Hirwa group consisted of 12 animals: one adult male, six adult females, three juveniles and two infants. All but one were sick. Two died: an adult female and a newborn infant.

Tissue analyses showed the biochemical signature of an RNA virus called human metapneumovirus (HMPV) infecting both animals that had died. While the adult female gorilla ultimately died as a result of a secondary bacterial pneumonia infection, HMPV infection likely predisposed her to pneumonia. HMPV was also found in the infant gorilla, which was born to a female gorilla that showed symptoms of respiratory disease.

The study's UC Davis authors are Cranfield, Lowenstine and Kirsten Gilardi, co-director of the UC Davis Wildlife Health Center's Mountain Gorilla One Health Program. The lead author is Gustavo Palacios, a virologist at the Center for Infection and Immunity at Columbia University in New York. Other authors are from the Mountain Gorilla Veterinary Project, Columbia University and the Rwanda Development Board.

The research was supported by Google.org; the U.S. National Institutes of Health; the Emerging Pandemic Threats PREDICT program of the U.S. Agency for International Development; and a grant from the David and Lucile Packard Foundation.

About mountain gorillas

With only about 786 individuals left in the world, mountain gorillas are a critically endangered species. Mountain gorillas live in central Africa, with about 480 animals living in the 173-square-mile Virunga Volcanoes Massif, which combines Volcanoes National Park in Rwanda, Virunga National Park in the Democratic Republic of Congo, and Mgahinga National Park in Uganda. The remaining population lives within the boundaries of the 128-square-mile Bwindi Impenetrable National Park in Uganda.

About the Mountain Gorilla Veterinary Project

The Mountain Gorilla Veterinary Project, a U.S.-based nonprofit organization, is dedicated to saving mountain gorilla lives. With so few animals left in the world today, the organization believes it is critical to ensure the health and well being of every individual possible. The organization's international team of veterinarians, the Gorilla Doctors, is the only group providing wild mountain gorillas with direct, hands-on care. The Mountain Gorilla Veterinary Project partners with the UC Davis Wildlife Health Center to advance "one-health" strategies for mountain gorilla conservation. http://www.gorilladoctors.org.

Chemists' Biosensor May Improve Food, Water Safety and Cancer Detection

ScienceDaily (Mar. 29, 2011) — A nanotechnology-based biosensor being developed by Kansas State University researchers may allow early detection of both cancer cells and pathogens, leading to increased food safety and reduced health risks.

Lateef Syed, doctoral student in chemistry, Hyderabad, India, is developing the biosensor with Jun Li, associate professor of chemistry. Their research focuses on E. coli, but Syed said the same technology could also detect other kinds of pathogens, such as salmonella and viruses.

"Kansas is a leading state in meat production and the poultry industry," he said. "Any outbreak of pathogens in these industries causes huge financial losses and a lot of health risks. We want to prevent these outbreaks by detecting pathogens at an early stage."

Syed's recent research poster, "Dielectrophoretic Capture of E. coli at Nanoelectrode Arrays," was named a winner at the recent Capitol Graduate Research Summit in Topeka. An article on this work has been accepted for publication in the scientific journal Electrophoresis.

For more than three and a half years, Syed's research has focused on developing nanotechnology-based biosensors for pathogen detection and cancer biomarker detection. He began the research as a doctoral student under the direction of Li, who has researched nanotechnology for 15 years.

The project is a continuation of work that Li performed at the NASA Ames Research Center in California, where he spent seven years developing nanotechnology. While working in California, Li came up with the idea of developing a small chip to capture and detect pathogens.

When Li arrived at K-State in 2007 he continued the biosensor research with Syed. Together they are working on developing biosensors for cancer diagnosis and pathogen detection. To develop these biosensors, the team uses carbon nanofibers, or CNFs, because they can form an array of tiny electrodes that is even smaller than bacteria and viruses. When these microbial particles are captured at the electrode surface, an electric signal can be detected.

"A goal is to integrate this technology into a hand-held electronic device for pathogen detection so that we can use this device for in-line monitoring of water quality or food quality at industrial processing sites," Syed said. "We have some preliminary results that indicate this technology is feasible, and I'm quite happy about that."

"We're still working with the company and trying to eventually deliver this as a product to feed the market for water quality monitoring," Li said. "You don't want people to drink contaminated water and get sick before you can do something. This research can be very helpful in the future as it can be applied in the very early stages before an outbreak spreads.

"Nanotechnology is a diverse field, and includes such biosensor devices that we can develop in this lab at the university," he said.

New Cancer Drug Heads to Clinical Trials

ScienceDaily (Mar. 29, 2011) — Researchers at the University of Michigan Comprehensive Cancer Center have developed a new drug called AT-406 with potential to treat multiple types of cancer.

AT-406 binds directly to the proteins that block cell death.

A study, published this week in theJournal of Medicinal Chemistry, showed that AT-406 effectively targets proteins that block normal cell death from occurring. Blocking these proteins caused tumor cells to die, while not harming normal cells. The researchers believe the drug could potentially be used alone or in combination with other treatments.

The normal cell death process, called apoptosis, is what keeps normal cells in check. When apoptosis is disrupted, cells reproduce uncontrollably, which is a hallmark of human cancer.

"Removing key apoptosis blockades in tumor cells is a completely new cancer therapeutic approach and could have benefit for the treatment of many types of human tumors," says study author Shaomeng Wang, Ph.D., Warner-Lambert/Parke-Davis Professor in Medicine and director of the Cancer Drug Discovery Program at the U-M Comprehensive Cancer Center.

Wang's laboratory has been pursuing new cancer treatments aimed at this cell death pathway since 2003. His team designed and made AT-406 and tested it in the laboratory in 2006. The small-molecule drug hones in directly on the proteins -- called inhibitor of apoptosis proteins or IAPs -- that block cell death. The researchers found that AT-406 destroyed these proteins in cancer cells. Meanwhile, the drug had little to no effect on normal cells.

In animal models, the drug shrank tumors but caused few side effects. The drug is designed to be taken by mouth, which researchers say will make it easier than traditional intravenous chemotherapies to administer.

Patent applications covering the drug are exclusively licensed to Ascenta Therapeutics, a privately-held, clinical stage biopharmaceutical company co-founded by Wang. After extensive testing, Ascenta began the first clinical trial in 2010 testing AT-406 for cancer treatment. This trial, which is being tested in all solid tumors, is offered at the U-M Comprehensive Cancer Center, Duke University and the Mayo Clinic. Ascenta has also recently opened a second trial of AT-406 in high-risk acute myeloid leukemia at the U-M Comprehensive Cancer Center. Several more clinical trials are planned.

"Our research goal and our passion is to translate our science and discovery into new and effective medicines for patients," Wang says. "I am delighted to see the drug we have designed, made and tested in our laboratory now being given to patients right here in the same building."

Additional authors: Qian Cai, Haiying Sun, Yuefeng Peng, Jianfeng Lu, Zaneta Nikolovska-Coleska, Donna McEachern, Liu Liu, Su Qiu, ChaoYie Yang, Rebecca Miller, Han Yi, Tao Zhang and Duxin Sun, all from U-M; Sanmao Kang, Ming Guo, Lance Leopold and Dajun Yang, all from Ascenta Therapeutics

Funding: Breast Cancer Research Foundation, National Cancer Institute, Ascenta Therapeutics and the University of Michigan Comprehensive Cancer Center.