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UCSF may have cure for deadly disease Chagas
Carol Lloyd, Special to The Chronicle
Sunday, February 14, 2010
(02-14) 04:00 PST Anatuya, Argentina --
Government health workers "came and tested me," the single mother said with a wan smile. She stood in front of her stick-and-mud shack on a patch of dirt in this dusty northern town of 20,000 residents. With her four barefoot children squatting nearby, Susana shrugged and didn't answer when asked her surname.
Though only in her 20s, Susana suffers from heart palpitations and tires easily. Like the estimated 25 percent of the population here who share her malady, she is unable to join her neighbors as seasonal workers on huge soy farms and depends on government subsidies to feed her family.
If a screenwriter set out to invent a disease for a grade-B horror flick, he could hardly do better than describe Susana's illness, which attacks cell walls like an army of tiny soldiers - Chagas disease.
Chagas is named for Brazilian physician Carlos Chagas, who in 1909 discovered the disease contracted by the bite of a beetle dubbed the "kissing bug" for its propensity to strike near the mouth.
The beetle sucks the blood of its sleeping victim before defecating on the itchy wound. Victims then unwittingly scratch the infected excrement into their bloodstream, where it gradually destroys heart tissue and the gastrointestinal tract. There is no cure and few treatments exist.
"They break through cell walls, get inside and replicate," explained Patricia Doyle, a parasitologist at UCSF's Sandler Center for Basic Research in Parasitic Diseases, a nonprofit that is seeking a cure for the disease that has infected an estimated 13 million people worldwide, including 3 million in Argentina and 300,000 in the United States.
Because the kissing bug thrives mostly in rural shacks, mud huts and thatched-roof homes, it primarily afflicts the poor, who become too sick to care for their families.
"It's devastating on many levels," said parasitologist Martin John Rogers of the National Institutes of Health.
Chagas is one of the so-called neglected diseases - forgotten by drug companies driven to maximize profits. Currently, only two treatments exist - benzimidazole and nifurtimox - and both are known to cause severe neurological damage and allergic reactions.
Nifurtimox is neither FDA-approved nor currently in production, forcing American doctors to petition the Centers for Disease Control and Prevention for its limited supply of benzimidazole.
But at UCSF's Sandler Center, there is a palpable sense of optimism that a cure is on the way. The first organization of its kind, the nonprofit group aims to do the seemingly impossible - discover and develop drugs for neglected diseases without a major for-profit partner.
By putting organic chemists, biophysicists, parasitologists and cell biologists into the same laboratories, the scientists collaborate to find a cure. By hiring experts on the FDA approval process, the center hopes academic science can not only conduct research but also develop treatments for neglected diseases.
The center is "an ideal place to perform research and develop drugs for neglected diseases in an independent fashion," said Dr. Miriam Postan of the National Institute of Parasitology in Buenos Aires.
After testing more than 2,000 compounds in test tubes, mice, rats, dogs and monkeys, the center's team, which includes husband-and-wife parasitologists Patricia Doyle and Juan Engel, has produced what it hopes is the first new treatment for Chagas ready for human testing in 35 years.
It's a protease inhibitor called K777, the same class of medication used to treat HIV.
Rogers, who manages parasitic drug development research for the National Institute of Allergy and Infectious Diseases at the National Institutes of Health, says K777 could be far safer and more effective than the two current treatments in part because it involves a shorter dosage, and targets only one parasite protein.
In animal trials, K777 killed the parasite without side effects, Doyle and Engel say.
Moreover, after mice were injected with lethal levels of the parasite and treated with K777, they appeared to be parasite-free.
Human testing can begin as soon as the FDA gives approval to begin preclinical trials - a process that can take a year or longer.
But even if tests proceed without a hitch, Rogers says, the process could be hindered by the very nature of the disease because it takes as many as six years to know if the parasites have been removed from the body.
Regardless, some experts note that K777 is important for showing that academic laboratories can make important drug discoveries.
"The K777 development story is exciting at all levels," said William Roush, director of Medicinal Chemistry at Scripps Florida University. "It is an extremely rare example of drug discovery and development in an academic laboratory."
No matter how effective it is, the drug's fate hangs in the balance. With no deep-pocketed partners in the wings, Sandler Center will proceed alone on a philanthropic shoestring.
"It comes down to money," said Tracy Saxton, who manages the center's FDA-approval process. "For-profit companies can spend $1 billion getting a new drug approved. We'll need to do it for a fraction of that."
For Susana, who lives miles from the closest hospital and monitoring team that Chagas requires, the hope of a wonder drug that will cure her symptoms seems an unlikely development.
When asked if she would seek treatment if scientists came up with a cure, she shrugged her shoulders and said nothing.
Neglected diseases
The so-called neglected tropical diseases are endemic among the poor in developing nations in Asia, Africa and Latin America. They include parasitic, bacterial and viral infections that can cause severe disability, deformity or death, and are typically spread by insects - mosquitoes, blackflies, sandflies, tsetse flies - or contaminated water and soil. According to the World Health Organization, more than 1 billion people suffer from one or more of these diseases, which include elephantiasis, snail fever (schistosomiasis), leishmaniasis and sleeping sickness.
But perhaps the most neglected of these diseases is Chagas, which threatens 100 million people, mostly in Latin America. It is responsible for an estimated 14,000 deaths a year, is the leading cause of heart attacks in the region and kills more people there than dengue fever, malaria and hepatitis C put together, according to the Pan American Health Organization.
It has been more than 100 years since Brazilian physician Carlos Chagas identified the Trypanosoma cruzi parasite that causes the disease and carries his name.
Its three stages make Chagas difficult to recognize. At first, symptoms may mimic those of a common flu, including fever and nausea. It can then remain dormant for 10 to 30 years, during which parasites gradually destroy heart tissue and the gastrointestinal tract. Most victims contract the disease as children and many are never aware of their illness.
"Young people with Chagas can be healthy one minute, then drop dead the next day from heart failure," said parasitologist Martin John Rogers of the National Institutes of Health.
In Chagas' last stage, the victim experiences fatigue, shortness of breath, heart palpitations and cardiac arrest. Once the disease has progressed to this phase, there is no cure.
Current treatments have potential fatal side effects and limited efficacy. In fact, many doctors refrain from treating the disease for fear of the treatment's toxicity, though new research suggests this is a mistake.
- Carol Lloyd
Carol Lloyd traveled to Argentina on a grant from Kaiser Family Foundation in Global Health Reporting.
This article appeared on page A - 17 of the San Francisco Chronicle
UCSF may have cure for deadly disease Chagas
Carol Lloyd, Special to The Chronicle
Sunday, February 14, 2010
(02-14) 04:00 PST Anatuya, Argentina --
Government health workers "came and tested me," the single mother said with a wan smile. She stood in front of her stick-and-mud shack on a patch of dirt in this dusty northern town of 20,000 residents. With her four barefoot children squatting nearby, Susana shrugged and didn't answer when asked her surname.
Though only in her 20s, Susana suffers from heart palpitations and tires easily. Like the estimated 25 percent of the population here who share her malady, she is unable to join her neighbors as seasonal workers on huge soy farms and depends on government subsidies to feed her family.
If a screenwriter set out to invent a disease for a grade-B horror flick, he could hardly do better than describe Susana's illness, which attacks cell walls like an army of tiny soldiers - Chagas disease.
Chagas is named for Brazilian physician Carlos Chagas, who in 1909 discovered the disease contracted by the bite of a beetle dubbed the "kissing bug" for its propensity to strike near the mouth.
The beetle sucks the blood of its sleeping victim before defecating on the itchy wound. Victims then unwittingly scratch the infected excrement into their bloodstream, where it gradually destroys heart tissue and the gastrointestinal tract. There is no cure and few treatments exist.
"They break through cell walls, get inside and replicate," explained Patricia Doyle, a parasitologist at UCSF's Sandler Center for Basic Research in Parasitic Diseases, a nonprofit that is seeking a cure for the disease that has infected an estimated 13 million people worldwide, including 3 million in Argentina and 300,000 in the United States.
Because the kissing bug thrives mostly in rural shacks, mud huts and thatched-roof homes, it primarily afflicts the poor, who become too sick to care for their families.
"It's devastating on many levels," said parasitologist Martin John Rogers of the National Institutes of Health.
Chagas is one of the so-called neglected diseases - forgotten by drug companies driven to maximize profits. Currently, only two treatments exist - benzimidazole and nifurtimox - and both are known to cause severe neurological damage and allergic reactions.
Nifurtimox is neither FDA-approved nor currently in production, forcing American doctors to petition the Centers for Disease Control and Prevention for its limited supply of benzimidazole.
But at UCSF's Sandler Center, there is a palpable sense of optimism that a cure is on the way. The first organization of its kind, the nonprofit group aims to do the seemingly impossible - discover and develop drugs for neglected diseases without a major for-profit partner.
By putting organic chemists, biophysicists, parasitologists and cell biologists into the same laboratories, the scientists collaborate to find a cure. By hiring experts on the FDA approval process, the center hopes academic science can not only conduct research but also develop treatments for neglected diseases.
The center is "an ideal place to perform research and develop drugs for neglected diseases in an independent fashion," said Dr. Miriam Postan of the National Institute of Parasitology in Buenos Aires.
After testing more than 2,000 compounds in test tubes, mice, rats, dogs and monkeys, the center's team, which includes husband-and-wife parasitologists Patricia Doyle and Juan Engel, has produced what it hopes is the first new treatment for Chagas ready for human testing in 35 years.
It's a protease inhibitor called K777, the same class of medication used to treat HIV.
Rogers, who manages parasitic drug development research for the National Institute of Allergy and Infectious Diseases at the National Institutes of Health, says K777 could be far safer and more effective than the two current treatments in part because it involves a shorter dosage, and targets only one parasite protein.
In animal trials, K777 killed the parasite without side effects, Doyle and Engel say.
Moreover, after mice were injected with lethal levels of the parasite and treated with K777, they appeared to be parasite-free.
Human testing can begin as soon as the FDA gives approval to begin preclinical trials - a process that can take a year or longer.
But even if tests proceed without a hitch, Rogers says, the process could be hindered by the very nature of the disease because it takes as many as six years to know if the parasites have been removed from the body.
Regardless, some experts note that K777 is important for showing that academic laboratories can make important drug discoveries.
"The K777 development story is exciting at all levels," said William Roush, director of Medicinal Chemistry at Scripps Florida University. "It is an extremely rare example of drug discovery and development in an academic laboratory."
No matter how effective it is, the drug's fate hangs in the balance. With no deep-pocketed partners in the wings, Sandler Center will proceed alone on a philanthropic shoestring.
"It comes down to money," said Tracy Saxton, who manages the center's FDA-approval process. "For-profit companies can spend $1 billion getting a new drug approved. We'll need to do it for a fraction of that."
For Susana, who lives miles from the closest hospital and monitoring team that Chagas requires, the hope of a wonder drug that will cure her symptoms seems an unlikely development.
When asked if she would seek treatment if scientists came up with a cure, she shrugged her shoulders and said nothing.
Neglected diseases
The so-called neglected tropical diseases are endemic among the poor in developing nations in Asia, Africa and Latin America. They include parasitic, bacterial and viral infections that can cause severe disability, deformity or death, and are typically spread by insects - mosquitoes, blackflies, sandflies, tsetse flies - or contaminated water and soil. According to the World Health Organization, more than 1 billion people suffer from one or more of these diseases, which include elephantiasis, snail fever (schistosomiasis), leishmaniasis and sleeping sickness.
But perhaps the most neglected of these diseases is Chagas, which threatens 100 million people, mostly in Latin America. It is responsible for an estimated 14,000 deaths a year, is the leading cause of heart attacks in the region and kills more people there than dengue fever, malaria and hepatitis C put together, according to the Pan American Health Organization.
It has been more than 100 years since Brazilian physician Carlos Chagas identified the Trypanosoma cruzi parasite that causes the disease and carries his name.
Its three stages make Chagas difficult to recognize. At first, symptoms may mimic those of a common flu, including fever and nausea. It can then remain dormant for 10 to 30 years, during which parasites gradually destroy heart tissue and the gastrointestinal tract. Most victims contract the disease as children and many are never aware of their illness.
"Young people with Chagas can be healthy one minute, then drop dead the next day from heart failure," said parasitologist Martin John Rogers of the National Institutes of Health.
In Chagas' last stage, the victim experiences fatigue, shortness of breath, heart palpitations and cardiac arrest. Once the disease has progressed to this phase, there is no cure.
Current treatments have potential fatal side effects and limited efficacy. In fact, many doctors refrain from treating the disease for fear of the treatment's toxicity, though new research suggests this is a mistake.
- Carol Lloyd
Carol Lloyd traveled to Argentina on a grant from Kaiser Family Foundation in Global Health Reporting.
This article appeared on page A - 17 of the San Francisco Chronicle