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Hope, humanity, and Huntington's disease in Latin America
In Context
Hope, humanity, and Huntington’s disease in Latin America Latin America—and Venezuela in particular—is home to the world’s largest, most studied, and often most resource-challenged populations affected by Huntington’s disease. The aim of Factor-H, a newly launched humanitarian project, is to improve the social conditions of people living with Huntington’s disease across the continent. But why could this project also be important in the search for a cure? Adrian Burton reports. A thrilling tango concert in the Sheraton Hotel, Mendoza, Argentina—what could this event have to do with the lives of people affected by a movement disorder living in the shanty towns around Venezuela’s Lake Maracaibo? In fact, a great deal, for this fundraising event marked the launch on October 12, 2012, (during the second International Workshop on Movement Disorders) of Factor-H, a humanitarian project that aims to improve the lives of those living with Huntington’s disease in Latin America, especially those who are also affected by pressing material need. Factor-H is the brainchild of Ignacio Muñoz-Sanjuan (CHDI Foundation, Los Angeles, CA, USA). A molecular and neurodevelopmental biologist, he coordinates the activity of some 300 researchers worldwide, who together are looking for ways to beat this disease. “But while we do that, we need to do something for the lives of those affected in Latin America”, he explains. “There are more people affected by Huntington’s disease here than anywhere else. Given its genetic nature, and the history of colonisation of the continent, Huntington’s disease tends to appear in often fairly large and welldefined clusters, for example in the well known concentrations around Lake Maracaibo in Venezuela, and others in Colombia, Peru, and Brazil. In some of these populations the prevalence is a staggering 1000 times that of other parts of the world, reaching 2450 per 100 000 inhabitants. These people and their families commonly have low incomes and experience difficulty www.thelancet.com/neurology Vol 12 February 2013
accessing social services and sufficient medical care. Indeed, families may have to care for several afflicted members in different stages of the disease, and in challenging living conditions. The aim of Factor-H is to enhance the quality of life of these families, to increase awareness of the communities most affected, mobilise communities to provide social and medical assistance, publicise the needs of these people and raise funds to meet them, and influence legislative issues that will facilitate access to government assistance.” A major role of Factor-H is that of facilitator, identifying needs with local and national associations, contacting parties that can provide solutions, and raising funding to implement them. For example, “Factor-H and Habitat for Humanity are currently evaluating the possibility of providing housing solutions to affected families in Argentina, Brazil, Chile and Colombia”, says Eugenia Salazar (Habitat for Humanity, San Jose, Costa Rica). “As we expand we also expect to be building care facilities, providing medical help, educational programs and perhaps even schools for affected communities”, adds Muñoz-Sanjuan. Improving the lives of people with the disease living in Venezuela’s Lake Maracaibo community is something that Factor-H committee member Claudia Perandones (Buenos Aires, Argentina) describes as a particular debt that wider society needs to repay. “Latin America has a special place in the history of Huntington’s disease. Therapeutically speaking, what we can do today has largely been made possible by the constant good will and collaboration of the
Lake Maracaibo people. Yet, they remain terribly afflicted by the disease, despite the tremendous efforts of groups like the Venezuelan Huntington’s Disease Association to provide informational, educational, and moral support to those affected. Moreover, these families commonly have to struggle with scant material resources, informal employment, and inadequate housing in which several families may live together and that frequently floods in the rainy season. We should be able to give them something better than this for what they have contributed towards research efforts.” That contribution has not been small. The large number of affected people living around the lake, and their large families, led pioneering scientist Nancy Wexler (Columbia University, New York, USA) to the region in 1979 to look for genetic clues to the disease. Between then and 2002, when Wexler ended her annual visits, the community provided blood and tissue samples (over 4000 cell lines in laboratories worldwide come from its members), permitted DNA and cognitive testing, and helped to trace out the lineages of over 18 000 people spanning ten generations and making up 83 affected kindreds. This collaboration allowed Wexler, and the Hereditary Disease Foundation she heads, to make the great discoveries in the field of Huntington’s disease, including the identification of the chromosomal location of the huntingtin gene in 1983, the isolation of the gene itself in 1993, the expanding CAG repeat nature of the disease mutation, how the number of CAG repeats affects the
For more on Factor-H (Hope, Huntington’s and Humanity) see http://factor-h.org For more on the CHDI Foundation see http:// chdifoundation.org For more on the Habitat for Humanity see http://www. habitat.org/ For more on the Hereditary Disease Foundation see http:// www.rlah.org/
133
In Context
For more on Enroll-HD see http://clinicaltrials.gov/ct2/ show/NCT01574053
Simon Podgorsek
For more on the Latin American Network on Huntington’s Disease, see http://www.rlah. org/
age of onset, and how these factors do not, in fact, explain everything— that a combination of unknown environmental and genetic factors is involved. “This environmental involvement gives Factor-H’s humanitarian work a scientifically important side”, explains Perandones. “Imagine one day that there is some hopeful treatment to try. Where would you want to perform a trial in people yet to develop clinical disease? In the Lake Maracaibo community, of course. But how would you separate out all the possible environmental confounders in a population subject to poor nutrition, with its members living in the conditions they do, and where people might die from anything from diarrhoea to septicaemia before you ever knew if the treatment had worked?” There are also other reasons for improving the conditions and infrastructures in which trials could be undertaken. “Clinical trials are actually essential for far more than testing new treatments”, says Trudie Lang (University of Oxford, Oxford, UK). “They are also important for evaluating pragmatic improvements in health management practices and interventions. Such studies could make real improvements to these Huntington’s communities, although they’d need to be locally led to ensure data are relevant to the environment
House built on Lake Maracaibo, Venezuela
134
and valued. Equipping local healthcare workers with the skills, resources, and support to identify and conduct pragmatic research studies would first bring improvements in health and later a platform for regionally led drug trials.” “Groups like the Lake Maracaibo community are also essential for deciphering the genetic and environmental factors that affect the manifestation of the disease, its onset and progression”, says MuñozSanjuan, “but one must ask whether it’s ethical to ask them to participate while nothing is done to improve their living conditions.” Cristina Sampaio (CHDI Foundation, Princeton, NJ, USA) is keenly aware that research must be accompanied by social improvements for stricken communities. “We are currently consolidating a global research initiative [launched in June, 2012] called Enroll-HD, a novel observational, longitudinal study that combines two existing observational studies—“REGISTRY” in Europe and “COHORT” in North America and Australia—with information from new sites in Latin America and Asia. A common dataset will be collected across all sites. This research platform differs from Factor-H, which is more of an initiative for the delivery of information, social assistance, training and care. But for Enroll-HD to get reliable research data, the populations involved must enjoy a minimum standard of care, comfort, and wellbeing. Without this background they might not be able to fully participate. For example, without proper care of patients and their families, and reliable monitoring, checking for compliance with protocols would be extremely difficult. In the end it’s a cycle: better care of populations in need could lead to our gaining better knowledge of Huntington’s disease, which in turn could lead back to better care.” In February, 2010, a group of Latin American neurologists, European disease specialists, relatives of
patients, and the CHDI Foundation formed a committee to create a network that would promote and facilitate research: the Latin American Network for Huntington’s Disease. Researchers near, and representatives of, clinical sites across the region were identified, and so far 14 groups in Argentina, Brazil, Chile, Ecuador, Peru, and Venezuela have joined. Talks with the ministries of health and regional regulatory agencies are now underway in all these countries to guarantee that patients will be included into Enroll-HD in January, 2013. “Though details remain to be ironed out, for example the ethical use of samples taken from the Lake Maracaibo community and how information may be invested back into it, such as informing people of their genetic status, we are hopeful that agreements will soon be made”, says Olmedo Ferrer Ocando, Head of the Movement Disorders Unit at Maracaibo University Hospital. “Venezuela is looking into how it can improve the quality of the lives of its Huntington’s disease patients; indeed, it has just authorised the use of tetrabenazine, the only real treatment for reducing coreic movements. The country’s participation in Enroll-HD might help them further, as well as other patients worldwide.” The aim of Factor-H should not, however, be confused with any science-based agenda, insists MuñozSanjuan. “But those working in Huntington’s disease science should not divorce themselves from the suffering of Latin America’s disease victims—people who have given so much and who have received so little in return. It may not be any time soon that people with Huntington’s disease will be able to take a drug and perform tangos like the dancers at our launch event, but in the meantime, maybe we can make their lives just a little less difficult.”
Adrian Burton
www.thelancet.com/neurology Vol 12 February 2013
Hope, humanity, and Huntington’s disease in Latin America Latin America—and Venezuela in particular—is home to the world’s largest, most studied, and often most resource-challenged populations affected by Huntington’s disease. The aim of Factor-H, a newly launched humanitarian project, is to improve the social conditions of people living with Huntington’s disease across the continent. But why could this project also be important in the search for a cure? Adrian Burton reports. A thrilling tango concert in the Sheraton Hotel, Mendoza, Argentina—what could this event have to do with the lives of people affected by a movement disorder living in the shanty towns around Venezuela’s Lake Maracaibo? In fact, a great deal, for this fundraising event marked the launch on October 12, 2012, (during the second International Workshop on Movement Disorders) of Factor-H, a humanitarian project that aims to improve the lives of those living with Huntington’s disease in Latin America, especially those who are also affected by pressing material need. Factor-H is the brainchild of Ignacio Muñoz-Sanjuan (CHDI Foundation, Los Angeles, CA, USA). A molecular and neurodevelopmental biologist, he coordinates the activity of some 300 researchers worldwide, who together are looking for ways to beat this disease. “But while we do that, we need to do something for the lives of those affected in Latin America”, he explains. “There are more people affected by Huntington’s disease here than anywhere else. Given its genetic nature, and the history of colonisation of the continent, Huntington’s disease tends to appear in often fairly large and welldefined clusters, for example in the well known concentrations around Lake Maracaibo in Venezuela, and others in Colombia, Peru, and Brazil. In some of these populations the prevalence is a staggering 1000 times that of other parts of the world, reaching 2450 per 100 000 inhabitants. These people and their families commonly have low incomes and experience difficulty www.thelancet.com/neurology Vol 12 February 2013
accessing social services and sufficient medical care. Indeed, families may have to care for several afflicted members in different stages of the disease, and in challenging living conditions. The aim of Factor-H is to enhance the quality of life of these families, to increase awareness of the communities most affected, mobilise communities to provide social and medical assistance, publicise the needs of these people and raise funds to meet them, and influence legislative issues that will facilitate access to government assistance.” A major role of Factor-H is that of facilitator, identifying needs with local and national associations, contacting parties that can provide solutions, and raising funding to implement them. For example, “Factor-H and Habitat for Humanity are currently evaluating the possibility of providing housing solutions to affected families in Argentina, Brazil, Chile and Colombia”, says Eugenia Salazar (Habitat for Humanity, San Jose, Costa Rica). “As we expand we also expect to be building care facilities, providing medical help, educational programs and perhaps even schools for affected communities”, adds Muñoz-Sanjuan. Improving the lives of people with the disease living in Venezuela’s Lake Maracaibo community is something that Factor-H committee member Claudia Perandones (Buenos Aires, Argentina) describes as a particular debt that wider society needs to repay. “Latin America has a special place in the history of Huntington’s disease. Therapeutically speaking, what we can do today has largely been made possible by the constant good will and collaboration of the
Lake Maracaibo people. Yet, they remain terribly afflicted by the disease, despite the tremendous efforts of groups like the Venezuelan Huntington’s Disease Association to provide informational, educational, and moral support to those affected. Moreover, these families commonly have to struggle with scant material resources, informal employment, and inadequate housing in which several families may live together and that frequently floods in the rainy season. We should be able to give them something better than this for what they have contributed towards research efforts.” That contribution has not been small. The large number of affected people living around the lake, and their large families, led pioneering scientist Nancy Wexler (Columbia University, New York, USA) to the region in 1979 to look for genetic clues to the disease. Between then and 2002, when Wexler ended her annual visits, the community provided blood and tissue samples (over 4000 cell lines in laboratories worldwide come from its members), permitted DNA and cognitive testing, and helped to trace out the lineages of over 18 000 people spanning ten generations and making up 83 affected kindreds. This collaboration allowed Wexler, and the Hereditary Disease Foundation she heads, to make the great discoveries in the field of Huntington’s disease, including the identification of the chromosomal location of the huntingtin gene in 1983, the isolation of the gene itself in 1993, the expanding CAG repeat nature of the disease mutation, how the number of CAG repeats affects the
For more on Factor-H (Hope, Huntington’s and Humanity) see http://factor-h.org For more on the CHDI Foundation see http:// chdifoundation.org For more on the Habitat for Humanity see http://www. habitat.org/ For more on the Hereditary Disease Foundation see http:// www.rlah.org/
133
In Context
For more on Enroll-HD see http://clinicaltrials.gov/ct2/ show/NCT01574053
Simon Podgorsek
For more on the Latin American Network on Huntington’s Disease, see http://www.rlah. org/
age of onset, and how these factors do not, in fact, explain everything— that a combination of unknown environmental and genetic factors is involved. “This environmental involvement gives Factor-H’s humanitarian work a scientifically important side”, explains Perandones. “Imagine one day that there is some hopeful treatment to try. Where would you want to perform a trial in people yet to develop clinical disease? In the Lake Maracaibo community, of course. But how would you separate out all the possible environmental confounders in a population subject to poor nutrition, with its members living in the conditions they do, and where people might die from anything from diarrhoea to septicaemia before you ever knew if the treatment had worked?” There are also other reasons for improving the conditions and infrastructures in which trials could be undertaken. “Clinical trials are actually essential for far more than testing new treatments”, says Trudie Lang (University of Oxford, Oxford, UK). “They are also important for evaluating pragmatic improvements in health management practices and interventions. Such studies could make real improvements to these Huntington’s communities, although they’d need to be locally led to ensure data are relevant to the environment
House built on Lake Maracaibo, Venezuela
134
and valued. Equipping local healthcare workers with the skills, resources, and support to identify and conduct pragmatic research studies would first bring improvements in health and later a platform for regionally led drug trials.” “Groups like the Lake Maracaibo community are also essential for deciphering the genetic and environmental factors that affect the manifestation of the disease, its onset and progression”, says MuñozSanjuan, “but one must ask whether it’s ethical to ask them to participate while nothing is done to improve their living conditions.” Cristina Sampaio (CHDI Foundation, Princeton, NJ, USA) is keenly aware that research must be accompanied by social improvements for stricken communities. “We are currently consolidating a global research initiative [launched in June, 2012] called Enroll-HD, a novel observational, longitudinal study that combines two existing observational studies—“REGISTRY” in Europe and “COHORT” in North America and Australia—with information from new sites in Latin America and Asia. A common dataset will be collected across all sites. This research platform differs from Factor-H, which is more of an initiative for the delivery of information, social assistance, training and care. But for Enroll-HD to get reliable research data, the populations involved must enjoy a minimum standard of care, comfort, and wellbeing. Without this background they might not be able to fully participate. For example, without proper care of patients and their families, and reliable monitoring, checking for compliance with protocols would be extremely difficult. In the end it’s a cycle: better care of populations in need could lead to our gaining better knowledge of Huntington’s disease, which in turn could lead back to better care.” In February, 2010, a group of Latin American neurologists, European disease specialists, relatives of
patients, and the CHDI Foundation formed a committee to create a network that would promote and facilitate research: the Latin American Network for Huntington’s Disease. Researchers near, and representatives of, clinical sites across the region were identified, and so far 14 groups in Argentina, Brazil, Chile, Ecuador, Peru, and Venezuela have joined. Talks with the ministries of health and regional regulatory agencies are now underway in all these countries to guarantee that patients will be included into Enroll-HD in January, 2013. “Though details remain to be ironed out, for example the ethical use of samples taken from the Lake Maracaibo community and how information may be invested back into it, such as informing people of their genetic status, we are hopeful that agreements will soon be made”, says Olmedo Ferrer Ocando, Head of the Movement Disorders Unit at Maracaibo University Hospital. “Venezuela is looking into how it can improve the quality of the lives of its Huntington’s disease patients; indeed, it has just authorised the use of tetrabenazine, the only real treatment for reducing coreic movements. The country’s participation in Enroll-HD might help them further, as well as other patients worldwide.” The aim of Factor-H should not, however, be confused with any science-based agenda, insists MuñozSanjuan. “But those working in Huntington’s disease science should not divorce themselves from the suffering of Latin America’s disease victims—people who have given so much and who have received so little in return. It may not be any time soon that people with Huntington’s disease will be able to take a drug and perform tangos like the dancers at our launch event, but in the meantime, maybe we can make their lives just a little less difficult.”
Adrian Burton
www.thelancet.com/neurology Vol 12 February 2013