By IGNACIO MUÑOZ-SANJUÁN, ROGER CACHOPE, CLAUDIA PERANDONES
For far too long, the fears and difficulties that characterize the life of people affected by Huntington’s disease have surrounded them with misunderstandings and barriers, veritably excluding them. In many cases the sick and their families have experienced the tragedy of shame, isolation and abandonment. I speak to you, physicians, healthcare workers, volunteers of the associations that are involved with Huntington’s disease and with those who suffer from it. The service that you all provide is valuable, because it is surely your dedication and your initiative that give tangible shape to the hope and motivation of the families who trust in you. Lastly, geneticists and scientists are present here, who, for some time, sparing no energy, have dedicated themselves to studying and researching a treatment for Huntington’s disease. Clearly, there is a great deal of expectation surrounding your work: resting on your efforts are the hopes of finding the way to a definitive cure for the disease, but also of improving the living conditions of these brothers and sisters…”
With these words, Pope Francis addressed hundreds of HD families from all over the world who congregated at the Vatican on May 18, 2017, for the first ever acknowledgement by any world leader about the suffering of those afflicted by Huntington’s disease. The event, organized by Dr. Elena Cattaneo, Charles Sabine, and Drs. Claudia Perandones and Ignacio Muñoz-Sanjuán of Factor-H, was an attempt to increase awareness and channel aid to the people of Latin America, and particularly of Venezuela, who are living in extreme duress due to poverty and Huntington’s disease. We are living through an extraordinary period of hope for Huntington’s disease (HD) affected families. Both ASO and AAV mediated gene therapy trials are underway, targeting the Huntingtin gene, with the goal of halting disease progression. Never since the discovery of the HD mutation in 1993 have there been such high expectations for the development of effective therapies.
Significant advances in HD research benefitted greatly from several decades of field studies of Venezuelan populations afflicted by the disease, located on the western shores of Lake Maracaibo. In 1993, the work by the Huntington’s Disease Collaborative Research Group culminated in the discovery of the causative mutation in HD. Many other scientific and medical findings that have greatly impacted our understanding of the disease. These include the evidence for a toxic gain of function of the mutation through the study of homozygote individuals, and the identification of modifier genes that alter the age of onset of HD were made possible through the extensive participation of these Venezuelan HD patients, their families and their communities. In the words of Dr. Nancy Wexler, the pioneer scientist who led the work to identify the mutation that causes HD, “The Venezuelan kindreds represent the largest and best characterized HD population in the world. Twenty-three years of prospective studies—genetic, neurological, and cognitive—have been carried out with kindred members. We hope that the Venezuelans will be able to benefit fully from the results of the research, as they played such a critical role in making everything possible.”
Throughout Latin America there are a number of communities (or ‘clusters’) where the prevalence of HD is strikingly higher than in the average population. These clusters seem to have arisen from founder populations, thought to be of European origin, who arrived in the late 18th century, in Cañete (Perú), Juan de Acosta (Colombia) and the Zulia State in Venezuela. Having visited many of these communities, we have been struck by their commonalities: many HD families live in extreme poverty, their members are largely uneducated, and often lack access to basic necessities, such as fresh water, food, adequate housing, and basic care. In many locations, at-risk people have little or no access to primary medical care, let alone neurological or psychiatric medications. In addition, families experience fear from being ostracized by their communities and, oftentimes, fear of violence against them.
There is a dearth of in-depth studies describing the incidence of the disease in these countries. Based on our work, many families remain unknown to the health authorities and do not receive any medical or social assistance. There is a critical need to conduct a population census, nationally or regionally, in areas with the highest concentration of affected families. Factor-H aims to tackle the most significant problems surrounding these communities, at a social, medical, and institutional level. We provide financial assistance and work with local HD associations. Our aim is to establish a local infrastructure that will increase institutional support, provide opportunities to escape poverty, and enhance access to medicines and adequate care.
Factor-H And Groups in Vulnerable Situations: Definition and Context
The international community has made significant progress by admitting the existence of differences and peculiarities among individuals, who even though they are born “free and equal in dignity and rights,” require an acknowledgement of their “diversity.” The recognition that there are groups with peculiarities entails the need to adopt new instruments so as to do away with any discrimination they may be subjected to. The so-called groups in “vulnerable situations” find difficulties or may be deprived of the full exercise of their fundamental rights. At Factor-H, we have seen that Latin America has started important processes of regulatory reform, although the task is still far from finished. We should remember that this process does not end in the recognition of rights and their codification in internal regulations. In many instances, local institutions do not carry out positive actions so that the fundamental rights of individuals can be effectively exercised and fulfilled.
This raises a series of new goals and challenges. More than 70 years after the Universal Declaration of Human Rights was adopted, there are still are huge strides to be made to alleviate poverty and grant rights to individuals with disabilities or with mental conditions. Promoting and protecting these rights has been one of the cornerstones of Factor-H management. The traditional concept of “vulnerability” is associated to that of “weakness” and “incapacity” or “at risk.” It constitutes a devaluated identity of the group it qualifies, thus reinforcing its discrimination. Therefore, at Factor-H, we have found the “groups in vulnerable situations” expression more suitable, as it is a dynamic, modifiable characterization of a situation.
This “groups in vulnerable situations” expression is used to name those groups of people or sectors in the population that, for reasons inherent to their identity or health status, and by action or omission of state agencies, are deprived of the full enjoyment and exercise of their fundamental rights, from healthcare to myriad other specific needs. To address this, Factor-H is working on the preparation of a Latin American Consensus for Huntington’s Disease that can be used as a tool to promote the effective compliance with the standards for medical attention and healthcare of patients with such pathology in the region. This will be described in more detail below.
Focus On Families Living in Most Vulnerable Conditions
Currently, Factor-H is providing basic assistance to 63 families in Perú, 74 families in Colombia (mostly in the Caribbean Coast), and 175 families in San Luis and Barranquitas in Venezuela. We are also financially supporting all three patient associations in Venezuela. These include the national association based in Caracas, through which about 1,600 families with a history of HD have been identified. Help starts with identifying the need. Factor-H recently received a grant from Brystol Myers-Squibb (BMS) to generate an electronic database and conduct a survey of those with HD and at-risk, in the Colombian Caribbean region. We hope to expand this survey to Venezuela and Perú.
Given the extent of the COVID-19 pandemic in these countries, basic assistance in the form of food, masks, soap and disinfectants has become a high priority. Factor-H initiated a program in March to help during the pandemic, with a few grants from other NGOs. We have been able to expand our assistance programs to many families, though the funding only enables limited outreach. The local medical infrastructure has also been significantly impacted by the pandemic. Other than Bogotá, the Caribbean region of Colombia is the one that has been most affected by Covid-19. In response, we established an informal telemedicine program for Colombia and Venezuela. We have had reported cases of SARS-Cov2 infections amongst the families we support, although the extent of how the epidemic in Venezuela is affecting the patients is unknown, as testing is not widespread. Due to lack of medical centers near Barranquitas, it is likely that patients with symptoms are not being reported.
One of Factor-H’s priorities is providing for the most vulnerable families. We have specific programs for families and for children at-risk for HD living in extreme poverty. Through the kids’ program (Program ‘Abrazos’), now in its fifth year, we sponsor 37 at-risk children in Colombia and 101 children in the Zulia State in Venezuela. A recent effort with a local church in Barranquitas provides meals daily for approximately 350 children and 100 patients, a lifeline of support for this community. There is a lot of work to do in this area — even though we recently started a small reading program in Barranquitas, the vast majority of at-risk children do not even have adequate nutrition and do not attend school. Our priority goal of building future resilient communities necessitates a lasting educational program to enable the next generation to be self-sufficient and better educated about the disease.
Strategies to Enhance Medical Care
Latin America is one of the world regions with the most unequal access to financial and medical opportunities. Generally, many families with HD — particularly in rural areas — lack access to medicines and adequate care. In spite of the existence of excellent HD medical centers in the country, few patients have access to their services. In addition, there is a very unequal distribution of specialized neurologists and other medical professionals in the countryside, as opposed to access in the largest cities.
One of the largest HD clusters in the world is nestled in the impoverished neighborhood of San Luis in the oil-producing town of Maracaibo, Venezuela, in which roughly a third of all families have a history of HD (Perez et al., 2013). Our recent informal survey suggests that 10-15% of this population of 3,500 people is at risk for HD. Nancy Wexler founded a care center there named Casa Hogar Amor y Fe, which provided access to food and medications as well as housed 40 or so patients. However, this center has been closed for some time now, and patients lack adequate facilities.
The town of Barranquitas, 120 km away, has the largest known HD population in the world. There, a third of the population of about 7,000 people is thought to be at risk for HD. Barranquitas lacks a specialized care center and is by far the worst affected community in the world, in terms of the number of cases and wrenching poverty. The current political and economic instability in Venezuela, as well as toxic pollution in Lake Maracaibo, have severely impacted conditions for this community, where most of the population is unemployed. Just a few decades ago Venezuela was recognized as a country with the best prospects of economic and social growth in all of Latin America, including a health system that was considered one of the best in the region. But even back then, the HD families in San Luis and Barranquitas found themselves far from accessing the level of healthcare that anyone would expect, given their condition.
Things were not going very well for them even in the middle of an oil bonanza. Starting in 2010, it only grew worse, as Venezuela experienced the worst recent political and economic crisis of any country in the continent. Recent independent reports show how the unavailability of medicines in the whole country grew from 55% in 2014 to 88% in 2018. The percentage of operating hospital departments in the Zulia state, where San Luis and Barranquitas are located, was estimated to be under 30% in 2018. If the HD communities were at a disadvantage during the years of economic prosperity, the now decimated country-wide and state-wide conditions are bringing to them a new level of adversity. Many Venezuelans have had to leave the country, including many of the physicians and healthcare personnel that used to dedicate themselves passionately to the HD community.
By the end of 2018 the local primary care center in San Luis had lost its personnel, its equipment was vandalized, and in the end it had to close all activities. Processing samples for the HD genetic test has been suspended for years in Maracaibo due to delays reinstalling the equipment and needed maintenance. At that time, in an attempt to help the desperate patients and their caregivers, Factor-H organized a day of medical activities in the open patio of the local primary care center in San Luis, facing the Maracaibo lake, with invaluable help from the NGO “Primeros Auxilios LUZ” (PALUZ), formed by young physicians from the University of Zulia.
A day of medical activities is a good way to gauge the problem, solve acute conditions, and to obtain a snapshot of the situation in order to build a more strategic mid and long-term response. In 2019, Habitat LUZ, our main collaborating NGO associated with the University of Zulia and managed by architect Marina Gonzalez de Kauffman, helped organize events in San Luis, where a team of healthcare professionals evaluated 44 at-risk children and close to 70 HD patients. Volunteer physicians made two medical visits to Barranquitas, seeing a total of 39 HD patients and 65 at-risk children. In May of 2019, Factor-H established an agreement with a psychiatrist to start conducting weekly visits to San Luis, seeing an average of 25 patients per month. In addition, we have signed up collaborative agreements with the University of Zulia to continue regular medical visits to both towns — after the pandemic subsides.
Another big challenge has been procuring medicines and medical supplies. Finding even the most common antibiotics, anti-inflammatories or analgesics, not to mention specialized medicines for HD is an odyssey in Maracaibo. With the help of several physicians in European countries, as well as European and USA-based NGOs, medicines and supplies are regularly collected or purchased and shipped to Venezuela. Altogether, the collaboration with local and international NGOs, local universities, physicians and patient associations, has been essential for Factor-H to partially address the most critical medical needs of patients, caregivers and their families. Still, more resources are needed to secure a specialized interdisciplinary group that includes experts in neurology, neuropsychology, social work, physical, occupational and speech therapies, and other disciplines that target comprehensive treatment of the patients.
Along the Colombian Northern region, the economic and political situation is much different than the one in neighboring Venezuela, but in some respects, effective access to high quality medical care for the HD families is not that much different. Colombia is proud of having a high-enrollment general health system, legislation exists regarding rare diseases, and indicators of mortality and vaccination rate have improved sensibly in the last years. However, Colombia exhibits one of the highest degrees of inequality in the whole region. Top-tier hospitals exist in the biggest cities, with abundant specialists in movement disorders, multidisciplinary teams, and the latest medical technology.
However, communities in rural areas and small towns — even if not remote — face the other end of the spectrum. Many of the HD patients in Juan de Acosta, barely 40 minutes by car from one of the biggest cities in the country (Barranquilla; 1.2 million inhabitants), have not had any follow-ups by a neurologist for years. Most of them do not receive regular pharmacological treatment, and some of the few that do have reached that opportunity only after suing their insurance companies for them to fulfill their obligations. The conditions of the families are even more troublesome in the towns of Algarrobo, Sábanas de San Angel and El Difícil (which means The Difficult, in Spanish, as if names had permeating power on destiny). Located about 2.5 hours by car from the Cesar’s state capital of Valledupar, most of the HD families in those towns live in rural areas. For them, reaching primary medical care might take hours of travel through unpaved hilly roads that under certain circumstances can easily lead to a premature death.
This happened to our 8-year old friend Olver about a year ago. Factor-H has organized days of medical activities dedicated to assessing the situation and solving acute health issues, aiming to have those addressed through long-term programs. The strategy to solve the situation in Colombia, however, is entirely different from Maracaibo. For some HD family members, it implies helping them enroll in the general health system. Others need to know how to request medical appointments. Some others require legal advice on how to request medical services to their insurance companies. Factor-H has been exploring the possibility of establishing a collaboration with existing medical centers for an HD specialist to evaluate patients at these centers. This scenario would still require the commitment of the insurance companies to provide medications, supplies, or complex medical procedures.
Goals During the Pandemic and Beyond
In March, when it was clear that the COVID-19 pandemic would bring additional adversity to the HD communities in Latin America, Factor-H reconvened a team of medical professionals specializing in HD from Colombia, Venezuela, Argentina, Chile and the USA to strategize on how to provide healthcare access through telehealth during the pandemic. A system was put in place for our social agents to receive medical attention requests from the community, to be triaged and routed to the specialists. Since then, tens of patients or HD family members have been remotely interviewed and advised on general health issues, HD, or COVID-19.
Whenever possible, medicines, transportation or help for relatives to bring patients to medical centers has been provided. Our ultimate goal is to develop a local health infrastructure, in its broader possible sense, by training and hiring a multidisciplinary team of professionals to assist these patients. We are trying to launch the LA PEP program (“Latin American Professional Exchange Program) to bring best practices to these communities. One means to this goal is to identify and fund health professionals to visit HD centers of excellence in Spain, Chile, Colombia and Argentina to get training in broad disciplines — rehabilitation, psychiatry, neuropsychology, neurology, nursing and nutrition. Armed with this training, they can return and improve care in their communities. Similarly, we seek funding to bring professionals to the communities to reach the broader caregiver and medical community as part of the exchange strategy. Agreements have been signed between Factor-H and several centers of excellence to receive trainees, and we plan to start the program in 2021, assuming we can ensure financial support.
Community development and education strategies
Ultimately, the strategy Factor-H is adopting to benefit these communities requires a multidisciplinary approach to build resilient communities that can become self-sufficient economically, educationally and medically. In order to do this, Factor-H is developing strategies in the areas of education and community development that, when implemented, will significantly improve their opportunities in life. Medically, the establishment of HD care facilities remains the most sought-after goal for every HD community in Latin America. Recently, in collaboration with architecture students of Cal Poly Pomona Lyle Center in California, we designed a concept for a day center in Barranquitas, which we hope to build in 2021. The center (C.A.S.A Dignidad) will feature classrooms and meeting spaces where we can conduct medical and educational activities.
The center will be managed by Habitat LUZ through a board that will encompass medical professionals, education specialists and representatives from the local community. Collaborative agreements with local universities and hospitals, as well as non-profit organizations, will be the basis for the management of these care centers, which we hope to build and run in the towns with the highest number of affected families. In addition, we want to ensure better financial sustainability for HD families. Micro-financing programs facilitate escaping from poverty through a systematic investment in education and employment, based on individual aspirations and within a regional context. We will concentrate particular emphasis on youth and women, the two most disadvantaged populations. As part of our efforts to reach the broader community at a local level, we initiated a set of art projects (Program “Art4HD”) using street art murals and photography, led by artists DJLu and Vladimir Marcano, depicting the families affected by HD in Colombia and Venezuela.
We hope to expand these programs to other locations after the pandemic subsides. Finally, Factor-H actively engages local institutions and universities via traditional conferences and seminars. We are bringing together international groups of clinicians, scientists, social workers and representatives of the major community associations from Perú, Chile, Colombia, Puerto Rico, Venezuela and Colombia, along with at-risk youth and affected families from seven countries (co-organized with HDYO). Through these educational events, we are able to engage the local and global community, as well as attract attention of local government agencies and politicians to the plight of these families. There is a real opportunity to make a significant impact, since HD only affects a few thousand people in each country. With targeted programs and an adequately implemented legislative framework, we can change the reality of these communities for the better. With the newly initiated gene therapy trials, and other therapeutic strategies in the drug development pipeline, there is now the real hope of developing effective treatments. If we tackle the scientific and social aspects of the disease concurrently, we may hope for synergistic benefits that fundamentally alter the impact of HD in afflicted patients and their communities.
In order to do this, Factor-H needs the continued support from companies engaged in HD R&D and philanthropic individuals with an interest in HD. Given the contribution of these communities to reach the extraordinary moment we are living in the HD therapeutic space, we ought to come together and get organized to ensure they too benefit from these advances.