Toronto Star

A curse, and a cure?

- AMY DEMPSEY FEATURE WRITER

MEDELLIN, COLOMBIA— The man who would become known as Patient No. 1 was a 47-year-old farmer who had forgotten how to farm. His name was Pedro Julio, and his family had travelled through the mountains, on horseback and then by bus, to San Vicente de Paul hospital in Medellin. They wanted to know if Pedro Julio was developing the terrible sickness that had robbed his mother and grandmothe­r of their senses.

La bobera, they called it. The foolishnes­s. Dr. Francisco Lopera was the physician on staff that day, a few weeks before Christmas in 1984. He was a young neurology resident whose boyhood obsession with UFOs had sparked an early interest in astronomy, until he decided the mysteries of the human brain were more interestin­g.

Pedro Julio was a mystery that would define his career.

Lopera had never seen dementia in patients so young. Soon after, a lottery ticket seller from another rural town arrived with the same symptoms and family history. He was 45.

Intrigued, Lopera travelled through the countrysid­e to interview the families of the afflicted, who for centuries had believed the illness was a curse cast by a wronged priest or a virus caught by touching the bark of a rare tree.

In fact, Lopera discovered, the sickness was a genetic curse. It stems from a rare mutation on chromosome 14 that triggers an aggressive form of early-onset Alzheimer’s disease. The defective gene has been passed on for generation­s in Medellin and across Antioquia, a mountainou­s northweste­rn province where the warm and welcoming inhabitant­s are known as paisas, or country folk. Carriers of the paisa mutation, as researcher­s have named it, are guaranteed to develop the disease, usually in their 40s. Their children have a 50/50 chance of inheriting the same fate.

With his colleague, Lucia Madrigal, Lopera spent years scouring church archives for birth and death records, mapping genealogie­s and tracing the mutation’s origins to the 18th century. He and collaborat­ors have identified 25 families, totalling 5,000 members, who are at high risk of developing the disease. Roughly 1,000 carry the mutation.

Now, long after Pedro Julio’s death, the research has led to an unpreceden­ted $100million drug trial that may be the world’s best hope for an Alzheimer’s cure. It aims to prevent the disease in healthy people who are geneticall­y predestine­d to develop it. This is a departure from previous trials, which have tried to treat dementia in patients who already have it, with little success. Lopera and his collaborat­ors believe that hasn’t worked because the treatment has come too late.

The Colombian families are a near-perfect test group. Researcher­s hope that if the drug works for them, it could work for all types of Alzheimer’s.

The study is led by the neuroscien­ce department at the University of Antioquia, where Lopera has worked as a behavioura­l neurologis­t since the 1980s, in partnershi­p with the U.S.-based Banner Alzheimer’s Institute, and with funding from drug manufactur­er Genentech and the U.S. National Institutes of Health. Lopera is at the helm.

It is a particular­ly weighty responsibi­lity for a researcher whose intimate relationsh­ip with his subjects predates the drug trial, an unusual dynamic in the coolly detached world of scientific study. He has shared meals with the families, laughed and cried with them, played with their children and grandchild­ren. His heart has broken as some of those children have grown up and developed symptoms while others have abandoned their dreams to care for sick relatives.

“After 30 years of study with these families, they now have a realistic hope for a drug that could prevent or delay the disease’s symptoms,” the doctor says. “It’s something we have been waiting for a long time.”

Lopera, now 64, lives just outside Medellin in a villa nestled high in the hills on a property overlookin­g the Aburra Valley. Until recently it was just a plot of land where he planted trees on the weekends, a decade-long gardening project that is a testament to his focus and patience.

“I started to build this house to avoid stress,” Lopera says. He added a pool where the paisa families swim during his annual parties and a gazebo office where the research team gathers to brainstorm. “I always say if we cannot find a solution to the problem in there, there is no solution.”

Walking the stone pathways through his gardens one morning, Lopera, a trim man with feathery silver hair, seems as charmed by the beauty as his visitors. He is dressed casually in jeans and a maroon peasant shirt. Born and raised in Antioquia with a hiatus in Belgium for graduate school, he is typically paisa, with a hearty laugh and the easy demeanour of a man who appreciate­s life because he has seen how cruel it can be.

The trial is the ultimate test of the longheld and prevailing theory that a buildup of amyloid plaque in the brain is the main cause of Alzheimer’s, not a symptom. If the drug, crenezumab, sweeps amyloid away and prevents or delays onset of the disease, it would be a massive breakthrou­gh.

The prospect of a cure has given the families hope they have lacked for centuries. But with hope comes the possibilit­y of failure. The uncertaint­y amounts to enormous pressure for the doctor who has come to think of his patients as family.

Five thousand paisas are counting on him, and the world is watching. Adaughter cares for her mama For more than a decade, Yaned Florez has been witness to her mother’s unstoppabl­e decline. Maria Nelly Florez, once a vibrant matriarch who loved to sing and dance, now sits slouched in a wheelchair, moaning and gurgling, her dark eyes vacant. She cannot utter the words her daughter believes are trapped inside her.

“Sometimes she laughs, sometimes she cries,” Yaned says quietly through a transla- tor, wiping drool from her mother’s chin with a soft cloth as they sit in their home in Villatina, one of Medellin’s hillside slums.

“What is it?” Yaned asks. “Don’t cry, Mama.”

For Yaned, 35, this is the hardest thing about being a caregiver: watching her mother slowly disappear and knowing there is nothing she can do. There is no treatment for Alzheimer’s. Medication can ease some of the symptoms, but the disease is progressiv­e and fatal. In December last year, Maria Nelly could walk. A few months later, she couldn’t stand. Soon she will be confined to a bed. Yaned says it’s like being dead while you’re alive.

“My mom was everything to me,” Yaned says. “We were always her and me together, and to have her like this, it’s as if she isn’t here.”

Yaned lives with her mother, husband Carlos and two sons, 15 and 9, in a small concrete house on the edge of a hill. A photograph of Maria Nelly from a better time hangs on the wall in the front room. “We only have one Mama, one Mami, one Mother in this world, one life,” it reads in Spanish. “Don’t wait until tomorrow to tell her you love her.” The family survives on Maria Nelly’s meagre pension and the money Carlos earns as a dishwasher and car cleaner.

As a young mother, Maria Nelly supported seven children with a full-time job as a cleaner. When her mind began to unravel, co-workers stole money from her, says Yaned, knowing she wouldn’t remember she had been paid. By the time she was diagnosed with Alzheimer’s at 49, the family knew what to expect. Maria Nelly’s father had died with the sickness decades before, and Pedro Julio, Patient No. 1, was her uncle. Dr. Lopera and his colleagues have been in their lives since Yaned was a girl.

Support from the research team has been the one bright spot for Yaned, who is a full-time caregiver for her mother, while raising two boys. University psychologi­sts and social workers have helped her understand the disease. They have taught her vital nursing skills — how to lift her mother without injuring herself, how to change diapers and prevent bedsores. They have provided Yaned with a hospital bed and a wheelchair that she could never afford.

“A lot of (caregivers) abandon themselves,” says Lucia Madrigal, a nurse and psychologi­st who has been working with Lopera since the beginning, and knows the families intimately. “They don’t get showers, they get very depressed.” A small portion of the clinical trial budget is allotted to training programs. “Because if we don’t, who is going to look after them?”

Madrigal and her team are also helping Yaned, as best they can, confront a terrifying and unavoidabl­e truth: as she watches her mother unravel, she knows there is a

“A lot of (caregivers) abandon themselves. They don’t get showers, they get very depressed.” LUCIA MADRIGAL MEMBER OF RESEARCH TEAM, WHICH ALSO OFFERS ASSISTANCE TO FAMILIES

50-per-cent chance that will be her someday. Asked if any siblings have started developing symptoms, Yaned and her cousins exchange grave looks and nod yes. A sister.

Yaned is content to remain in the dark about her genetic status. If she knew she had the mutation, “I might do something crazy,” she says.

Earlier this year, she became a volunteer in the clinical trial. Every two weeks, she is injected with either the drug or a placebo — neither she nor the researcher­s know which. To protect the integrity of the clinical trial and shield the paisa families from prejudice, the University of Antioquia’s ethics committee requires journalist­s to shield the identities of the participan­ts they interview. For that reason, surnames in this story have been changed.

Yaned admits bashfully that she would like to return to school one day to study nursing, perhaps to help others manage the burden of caregiving. This is a dream for the future, after her mother has died, and one she isn’t even sure she could handle. But she holds on to the thought. The fate of the coffee farmer’s children When Alirio Gomez was barely old enough to understand suffering, his father sat him down and told him about La bobera.

There was no sense sheltering 5-year-old Alirio from the truth. As he grew up, he watched a dozen family members fall victim to Alzheimer’s disease. Aunties who didn’t remember who he was. An uncle tied to a bed, lying in his own feces. A cousin whose symptoms appeared at 33 and who was dead by 36.

Alirio knew the disease was hereditary, passed down from a grandmothe­r who died before he was born, but he and his eight siblings came to believe that their father, and thus their branch of the family, had been spared. German Gomez, a coffee farmer whose boys learned the trade by following him around the family’s small farm, made it through his 40s and 50s without developing symptoms. He worked hard, told jokes, played the fiddle.

But soon after he turned 67, German’s wife and grown children began to notice strange behaviour. He would rip a coffee plant from the ground, mistaking it for a weed. He would set down his coco, the belted bucket used to collect ripe beans, and forget where he left it.

“Dad, you’re getting sick in that way,” his sons told him. But German didn’t see it.

As the disease advanced, German forgot who his children were and didn’t recognize himself in the mirror. If his wife handed him a cigarette, he would offer it to his reflection. Sometimes he would linger, talking to the man in the mirror. By the time he died, at 73, he could only babble.

Now 42, Alirio is a husband and father with a coffee field of his own and a comfortabl­e home around the corner from where he grew up, in a quiet hamlet130 kilometres north of Medellin. On a recent afternoon, he sits in a gazebo overlookin­g the hills, relaxed as he watches his 6-year-old son, Alexis, manoeuvre a finicky kite in the wind — his12th of the season, Alirio says, because he keeps losing them in the trees. A smattering of houses dot the undulating landscape, many of them owned by his relatives.

So far, none of Alirio’s eight siblings, aged 41 to 52, has Alzheimer’s. “All fine and healthy at the moment,” he says. But genetics predict half of them will develop the disease.

That could change, of course, if the clinical trial leads to a treatment. All but two are volunteers in the study. They travel every other week to a research outpost in a nearby town, where they receive their injections with others who live too far north to make the trip to Medellin.

Alirio feels confident he’s been spared from the disease and says he doesn’t agonize over his fate. More than the sickness, he worries about being abandoned. His deepest fear stems from the memory of his uncle, tied to a bed with no one to look after him. His wife, Marta, a soft-spoken woman with kind eyes, places a hand on his shoulder and shakes her head. “I will look after him until the end,” she says firmly. “I will be with him until God separates us. God willing, he doesn’t have that sickness. That’s what we hope.”

Hope is what Lopera has given them. With a hand over his heart, Alirio describes the doctor as God on earth. He is touched that a person unaffected by the illness could care so much. “The kind of love that he shows to all of us when we all get together, for us around here who inherit the sickness, it’s very emotional to see,” he says.

“That’s what gives you strength. Knowing that you’re not alone, and that there are people that are fighting for you.”

Lopera and his team have taken care to instil optimism in the participan­ts while also preparing them for the possibilit­y of failure. It’s a delicate balance. But Alirio seems to embody the outlook they have strived to promote. “I understand, obviously, that the medicine might not work,” he says. “But I choose to stay positive because I know that they are working hard, and because if this one doesn’t work, they might be working on another one.” Alirio may be right. “We will all be very sad if it doesn’t work,” Lopera says. But, he adds, the paisa families know they won’t stop there. “This is not the only thing we can do. This is the first thing.”

Lopera hopes the next step will be to conduct a primary prevention trial — one in mutation carriers under the age of 28 who are not only asymptomat­ic, but whose brains lack any toxic amyloid buildup. Pharmaceut­ical companies have yet to come up with a suitable drug for such a study, but Lopera will be ready when they do.

It will take time, he says. “But they have patience, because all their lives they have been living with this tragedy.”

 ??  ?? Alirio Gomez in his living room with his son, Alexis, and his wife, Marta. Gomez, a coffee farmer, watched his father and a dozen relatives succumb to dement a participan­t in the study led by Dr. Francisco Lopera. “I understand, obviously, that the...
Alirio Gomez in his living room with his son, Alexis, and his wife, Marta. Gomez, a coffee farmer, watched his father and a dozen relatives succumb to dement a participan­t in the study led by Dr. Francisco Lopera. “I understand, obviously, that the...
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 ?? STEVE RUSSELL PHOTOS/
TORONTO STAR ?? Yaned Florez has watched her once vibrant mother, Maria Nelly Florez, slowly succumb to earlyonset Alzheimer’s. “My mom was everything to me,” she says. Now, “it’s as if she isn’t here.”
STEVE RUSSELL PHOTOS/ TORONTO STAR Yaned Florez has watched her once vibrant mother, Maria Nelly Florez, slowly succumb to earlyonset Alzheimer’s. “My mom was everything to me,” she says. Now, “it’s as if she isn’t here.”
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 ??  ?? Dr. Francisco Lopera has spent 30 years studying the so-called paisa mutation that affects people in the region around Medellin.
Dr. Francisco Lopera has spent 30 years studying the so-called paisa mutation that affects people in the region around Medellin.
 ?? STEVE RUSSELL PHOTOS/TORONTO STAR ?? Alexis, 6, flies a kite at his home in the hills north of Medellin. By his age, his father, Alirio, already knew about la bobera, the dementia that ran in his family.
STEVE RUSSELL PHOTOS/TORONTO STAR Alexis, 6, flies a kite at his home in the hills north of Medellin. By his age, his father, Alirio, already knew about la bobera, the dementia that ran in his family.
 ??  ?? Yaned Florez cares for her mother, Maria Nelly Florez. Yaned, who is also a volunteer in the clinical trial, would like to return to school one day to study nursing.
Yaned Florez cares for her mother, Maria Nelly Florez. Yaned, who is also a volunteer in the clinical trial, would like to return to school one day to study nursing.
 ??  ?? tia. Gomez is now
tia. Gomez is now

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