Sought Out by Science, and Then Forgotten

José Echeverría spends restless days in a metal chair reinforced with boards and padded with a piece of foam that his mother, Nohora Vásquez, adjusts constantly for his comfort. The chair is coming loose and will soon fall apart. Huntington’s disease, which causes José to move his head and limbs uncontrollably, has already left one bed frame destroyed. At 42, he is still strong.

José’s sister Nohora Esther Echeverría, 37, lives with her mother and brother. Just two years into her illness, her symptoms are milder than his, but she is afraid to walk around her town’s steep streets, knowing she could fall. A sign on the front door advertises rum for sale that does not exist. The family’s scarce resources now go to food — José and Nohora Esther must eat frequently or they will rapidly lose weight — and medical supplies, like a costly cream for Jose’s skin.

Huntington’s is a hereditary neurodegenerative disease caused by excess repetitions of three building blocks of DNA — cytosine, adenine, and guanine — on a gene called huntingtin. The mutation results in a toxic version of a key brain protein, and a person’s age at the onset of symptoms relates, roughly, to the number of repetitions the person carries. Early symptoms can include mood disturbances — Ms. Vásquez remembers how her late husband had chased the children out of their beds, forcing her to sleep with them in the woods — and subtle involuntary movements, like the rotations of Nohora Esther’s delicate wrists.

The disease is relatively rare, but in the late 1980s a Colombian neurologist, Jorge Daza, began observing a striking number of cases in the region where Ms. Vásquez lives, a cluster of seaside and mountain towns near Barranquilla. Around the same time, American scientists led by Nancy Wexler were working with an even larger family with Huntington’s in neighboring Venezuela, gathering and studying thousands of tissue samples from them to identify the genetic mutation responsible.

This Colombian region is now thought to house the second largest extended family with Huntington’s. Its members are of intense scientific interest because they hold clues to genetic modifiers of, and potential treatments for, Huntington’s disease. Yet since Dr. Daza’s untimely death in 2014, they have been cut off from a world of promising experimental treatments, genetic counseling and often basic medical care. Ms. Vásquez, like others in her generation, occasionally calls the disease by its 16th-century name, San Vito, or St. Vitus’ dance.

The family members tend to come from the poorest segments of this coastal society: people who fish, clean beachside hotels or farm. Universities and health officials have shown up intermittently to take their blood samples, but no definitive epidemiological, clinical or genetic studies have been published. Few if any at-risk individuals know whether they are mutation carriers. Scientists are now trying to do better by them, hoping it’s not too late.

‘Like starting from zero’

In recent years, a group of researchers at the Universidad Simón Bolívar, in Barranquilla, have taken on the daunting task of rekindling clinical and genetic studies that stalled after the death of their colleague Dr. Daza. It felt, said neuropsychologist Johan Acosta, who is leading the effort, “like starting from zero.”

Out in the towns and villages, the investigators found the Huntington’s families wary and tired. Almost everyone reported having had a blood sample taken in the past and being confused as to what it had been used for. Events organized by the researchers were poorly attended, so “we had to look for people in their homes, to establish more direct contact,” said Elsy Mejía, a neuropsychologist.

The group’s project, which is sponsored by the Colombian government, focuses on the subtlest, non-motor symptoms of the disease. Investigators conduct clinical evaluations and brain imaging in early symptomatic or pre-symptomatic people, as well as in noncarriers with family histories of Huntington’s. DNA has now been collected from nearly 300 individuals, through which scientists hope to identify genetic links to early symptom patterns.

The researchers have promised to share findings from their studies with the family members, as well as results from clinical evaluations, although they cannot disclose genetic test results; that must wait until counseling is established. They offer help securing medicines and conduct daylong clinics in which any family member can see a doctor, for any reason.

In 2021, the team produced a primer on the disease and its history in the region, aimed at local health professionals who in many cases know little about it. They hope that the university will soon take part in Enroll-HD, a global platform to study people with Huntington’s disease and facilitate clinical trials.

They also know that if they — or other researchers — drop the ball with the family members, all will be lost. “This is not just science, this is social science,” said Pedro Puentes, a neuropsychologist and the leader of the research group. “People expect something” in return for what they’ve given, he added. “And as you can see, nothing really has been done for them.”

Mari and Julieta

Julieta Echeverría, 23, raises two young boys in a home perched over a sandy creek into which people toss refuse, as there are no roads fit for a garbage truck. The roof and walls of her house are badly cracked; one bedroom must be evacuated when it rains.

For months last year, Ms. Echeverría and her husband, a fisherman, nursed her bachelor uncle Nelson Echeverría through the end stages of Huntington’s disease. Her parents, who are farmers, could not care for Nelson because her father is also ill, although he has yet to see a neurologist. With hands now too unsteady to milk his cows, he survives on his wife’s sales of eggs.

In the nearby town of Juan de Acosta, Mari Echeverría, 22, recounted an almost parallel existence to that of Julieta, her first cousin. (The two are also first cousins of José and Nohora Esther.) Last year, as Julieta bathed her uncle, played music to cheer him up and fed him Ensure through a syringe, Mari was doing the same for her mother, who died one month after Nelson. Mari, like Julieta, was caring for a baby and a toddler at the time.

Mari was a teenager when her mother’s illness began, at age 42. Those were the days when Dr. Daza still came around in his van with drugs and reassurances. Both Mari’s mother and Nelson lived out the rest of their illnesses largely without standard medications, such as tetrabenazine to control movements and psychiatric drugs to calm emotions and promote sleep. Mari’s mother, a kind and curious woman before her illness, would at times get hold of a knife and throw it.

When Mari’s mother developed a fever, in her last weeks of life, Mari took her to a hospital in Barranquilla, where doctors did not recognize her symptoms, nor had they heard of her disease. “I had to write it out for them on the computer,” she recalled. “They asked me, ‘What treatment does your mother take?’ And I said, ‘What do I know about treatment?’”

Unlike their older relatives, who recall a time when the disease was hidden, denied or attributed to other causes, Julieta and Mari grew up aware that they each have a 50 percent likelihood of developing Huntington’s by midlife. Both opted to have children, with partners who understood that risk.

Julieta views the specter of Huntington’s with a certain resignation. “There are worse ways to die,” she said. But both she and Mari are taking part in the Universidad Simón Bolívar study. They also participate in events sponsored by Factor H, a Huntington’s charity active in Colombia and Venezuela that strives to connect researchers with families.

“We want to lose this lack of trust that exists between vulnerable communities and the doctors,” said Ignacio Muñoz-Sanjuan, the founder of Factor H and the chief executive of Cajal Neurocience, a Seattle-based drug-discovery company. “And for the clinicians and researchers to understand there are human beings behind what they are trying to do.”

A health care Catch-22

The CHDI Foundation in Princeton, N.J., a nonprofit group that supports Huntington’s drug research globally, is increasingly active in Latin America. One reason is genetics. “We have found a number of so-called modifiers among the European population, and these are targets for new drugs,” said Dr. Cristina Sampaio, CHDI’s chief medical officer. In Latin America, she added, “we might find other genes that influence how the disease progresses. These modifiers could become targets.”

Another reason is an abundance of younger, still-asymptomatic people. CHDI runs Enroll-HD, a global observational study of people with Huntington’s disease. Although most of its 25,000 participants so far have had advanced disease, “we have a really big scientific need to study people very early in the disease process,” Dr. Sampaio said. “Latin America may provide a place where we can find more of them, and these are the people who have the best opportunity to benefit from treatment.”

Enroll-HD cannot work in Venezuela, because of political obstacles, a degraded health infrastructure and extreme poverty. Even in Colombia, where much of the population receives quality health care, huge disparities persist. The investigators at Universidad Simón Bolívar are eager to take part in Enroll-HD, but it remains to be worked out who can be studied under the platform.

“In these villages, you have roads that are bad — doctors aren’t available,” said Dr. Sampaio, who visited last year. “We cannot do studies in populations that do not have access to minimal standards of care. So this might be a Catch-22 type situation. Engaging them in research raises ethical concerns, but if they were enrolled, their access to care would improve.” For now, Dr. Sampaio said, Enroll-HD plans to work only with people who live in Barranquilla or who have the wherewithal to get there.

Dr. Muñoz-Sanjuan of Factor H said he was optimistic that, with effort, conditions could be improved enough to allow people like Mari and Julieta to someday join a clinical trial.

“The obstacle on the coast has been fragmented efforts without a holistic approach,” he said. “People want help from a clinical and social perspective; we need access to people to develop better therapies. These two things have to be connected.”


Gepsy Ariza, 34, does not know how her family is related to others around the region, just that they are a Huntington’s family. A pensive young woman, she, too, recounts the experience of caring for an ailing mother, of Dr. Daza and his medicines, and of giving her blood to some neurology students, only to be told later that the samples had been lost.

In the dusty beach town where she lives, a short drive from Barranquilla yet a universe away from its comforts, Ms. Ariza helps look after her sister, Maripaz Ariza. At only 30, Maripaz has hands that fan and twist like a Balinese dancer’s, a wavering voice, and a stiff, awkward gait.

Maripaz’s symptoms emerged seven years ago, when she was pregnant with her daughter. The disease first manifested as an emotional crisis, Gepsy recalls. When Maripaz was in the hospital, waiting to give birth, she ran outside in a panic, upset that her child would be a girl, not the boy she had hoped for. Staff members called in social workers to investigate before allowing her to see her newborn.

The family history of Huntington’s was never explored. Maripaz was diagnosed with psychosis. Her behavior has grown more childlike as her motor symptoms have progressed, making her seem more like a friend than a parent to her little girl. When Maripaz first became sick, her uncle took Maripaz and her daughter into his home. He later died from Huntington’s, and now his widow looks after both.

Little is known about Huntington’s disease and pregnancy, so rare are the cases in the scientific literature. Seven years into her illness, Maripaz still has not seen a neurologist.

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