Dancing with Destiny: Nancy Wexler’s Quest to Unravel Huntington’s Disease
In the world of medical mysteries, there are often remarkable stories of individuals who dedicate their lives to unraveling the secrets behind devastating diseases. One such story begins with a woman named Nancy Wexler, whose personal connection to Huntington’s disease has shaped her mission to understand and combat this cruel condition.
Nancy’s journey began when her mother, Leonore Wexler was diagnosed with Huntington’s disease, a degenerative disorder that affects the brain. The disease, often referred to as Huntington’s chorea (chorea means dance in Greek), earned its tragic name due to the involuntary, jerky movements it induces, resembling a diabolic dance. Individuals who inherit Huntington’s disease typically enjoy a period of relative well-being during the initial three to four decades of their lives. They may exhibit sporadic shifts in mood or display subtle indications of social withdrawal.
Eventually, subtle tremors emerge, making it increasingly challenging for them to grasp objects. And then, the involuntary “dance” commences, as if orchestrated by an otherworldly conductor. Their hands and legs move of their own accord, performing movements interrupted by abrupt spasms (reminiscent of a grand puppet show where invisible strings control the giant figures). In the advanced stages of the disease, profound cognitive decline and near-total loss of motor control ensue. Malnutrition, dementia, and infections ultimately claim their lives, yet they continue to “dance” until the very end. Witnessing her mother’s suffering and the impact it had on their entire family, Nancy was compelled to make a difference.
Inspired by her mother’s battle, Nancy’s father, Milton Wexler, founded the “Hereditary Disease Foundation”. This organization was established in 1968 to support research into genetic disorders, with a particular focus on Huntington’s disease. Milton’s determination to find a cure for his wife and daughters fueled the family’s commitment to this cause.
Nancy and her sister, Alice, faced a 50% chance of inheriting the disease themselves. Tragically, Leonore’s life was cut short on May 14, 1978, which happened to be Mother’s Day. This devastating loss only strengthened Nancy’s resolve to combat the disease that had taken her mother’s life.
At that time, David Botstein, Ron Davis, Kerry Kravitz, and Ray White revolutionized genetic mapping through their pioneering work. They developed a method using genetic variations called polymorphisms to create detailed maps of the genome. But, to do that, they needed a huge sample of people with the disease, thus the United States was not the place for them.
In the 1950s, an intriguing observation came to light through the observations of Venezuelan neurologist Americo Negrette in Barranquitas, Venezuela. It was noted that both men and women residing in this region displayed a constellation of distressing symptoms, including dementia, facial tics, muscle wasting, and uncontrollable movements. It was soon discovered that this was a manifestation of Huntington’s disease, shedding light on the prevalence and impact of this devastating condition within the community.
Nancy, who heard about Negrette, traveled to Venezuela in 1979. Driven by a sense of urgency, Nancy and her dedicated team embarked on a remarkable journey. It was there that they discovered a unique opportunity to study the disease. In a small village, a large number of individuals were affected by Huntington’s disease, providing a valuable resource for research. Through meticulous investigation, the researchers stumbled upon a remarkable family consisting of 14 children. Recognizing the potential significance of their findings, they diligently collected information and expanded their search. Over several months, their efforts culminated in a comprehensive list encompassing hundreds of individuals — men, women, and children alike — afflicted by the relentless grip of Huntington’s disease.
Finally, a breakthrough came in the form of discovery — the localization of the gene responsible for Huntington’s disease on chromosome 4 in 1983, however, nearly a decade later, in 1992, a multinational team of 64 scientists successfully pinpointed the precise location of the gene responsible for Huntington’s disease. This significant discovery led to the christening of the gene as “huntingtin” marking a crucial milestone in our understanding of the disease’s genetic underpinnings.
Huntingtin is a protein encoded by the gene that carries the instructions for normal cellular function. However, in individuals with Huntington’s disease, an abnormality occurs due to an excess of CAG (cytosine-adenine-guanine) repetitions within the huntingtin gene. These CAG repetitions result in the production of a mutant huntingtin protein that disrupts crucial cellular processes, leading to the onset and progression of the disease.
The length of the CAG repeats directly affects the severity and age of onset of Huntington’s disease. Generally, the more repetitions, the earlier the symptoms appear and the more rapidly the disease progresses. In Venezuela, the impact of Huntington’s disease is reaching even younger individuals, with affected children as young as twelve years old. The severity of the disease is evident in certain cases, where chains of repetitions in the gene can extend to as many as seventy to eighty repeats. This discovery provided valuable insights into the underlying mechanisms of the disease and laid the foundation for future research and potential therapies.
Nancy Wexler’s tireless dedication and personal connection to Huntington’s disease have played a vital role in advancing our knowledge of this devastating condition. Her commitment, along with the efforts of countless researchers, has propelled us closer to finding a cure and providing hope for individuals and families affected by this debilitating disease.
As we continue to delve deeper into the complexities of Huntington’s disease, we must remember the profound impact it has on the lives of those who suffer from it. The story of Nancy Wexler and her journey serves as a reminder of the strength and determination needed to fight against such formidable adversaries. Together, we can strive towards a future where Huntington’s disease no longer steals the dance of life from its victims.
