One Family's Search to Explain a Fatal Neurological Disorder
With their help, researchers are advancing the 70-year effort to understand—and treat—hereditary ataxia.
Quest for a Cure
Henry dreamed of attending medical school to study ataxia and help his family. However, financial hardships during the Great Depression forced him to abandon his efforts to obtain a college degree. He returned home to the farm in 1934 and married in 1935. His cousin Ed also returned home to be closer to family after he was diagnosed with ataxia. He was a willing research participant and worked with Dr. Rossen at St. Peter's Hospital, where he donated cerebrospinal fluid for research. He was even directed to consume calf brains in hopes of identifying a potential treatment. Unfortunately, these efforts did not improve his condition.
Henry's younger brother, John, made it his goal to find a cure for the family disorder and studied to become a medical doctor. He began practicing as a neurologist in the mid-1940s. Dr. John, as family members called him, completed a comprehensive study of the ataxia that ran in his family, which was published in Archives of Neurology and Psychiatry in 1950. This article described the symptoms of the disease, the multigenerational nature of the disorder, and an interesting phenomenon regarding the ataxia in his family—family members were showing symptoms of the disorder at earlier and earlier ages, an effect called genetic anticipation. Genetic anticipation is common in some hereditary neurodegenerative disorders, such as Huntington's disease, but at the time no one knew why this accelerated timing would occur. In the hereditary ataxia that affected the Schut family, each generation that inherited ataxia was more severely affected by the disorder. Whatever factor caused the disease became more toxic to the body as it passed from parent to child.
In 1949 Dr. John returned to a medical residency program to become a certified neurologist. Meanwhile, his older sister, Elsie, had become severely affected by ataxia, and he was determined to do all he could to help her. With each minor illness, her lungs became filled with fluid that her body was unable to expel. She coughed, gasping for breath, and Dr. John frantically aspirated her lungs so that she could take another gulp of air. Her death in 1953, at age 36, was especially difficult for him; he had done everything he could to keep her alive. Now Dr. John was even more determined to identify the cause of ataxia, and time was beginning to run out: He himself was showing symptoms of the disease. He suspected that there must be a genetic factor. This idea was based on the observations that multiple generations within the family were affected and that the disease symptoms increased in severity as ataxia passed from generation to generation. If he identified the factor underlying the hereditary ataxia by finding genetic association, he could potentially treat the disorder.
Such research called for resources, so in 1957 Henry and Dr. John founded the National Ataxia Foundation to raise funds. Ataxia was nearly unheard of, so raising awareness about the disorder was necessary. Dr. John worked with another relative to educate the public about ataxia. Soon, he secured private and government funding to conduct genome association studies. At the time, no other families with SCA1 were known, so the studies focused only on affected members of his own kin.
Dr. John examined blood and cerebrospinal fluid from affected and unaffected individuals, but he did not find a blood factor associated with the disorder. However, in the cerebrospinal fluid from ataxic patients, he saw higher levels of compounds attributed to death of neuronal cells. These compounds were possible by-products of the disease, but alone they could not explain the cause of ataxia. Dr. John kept studying ataxia but made little progress. At the time, science lacked the necessary tools to identify the factor causing the disorder.
As more cousins became disabled by ataxia and his own illness worsened, the lack of answers was increasingly frustrating for Dr. John; conversely, the possibility of identifying genetic underpinnings became ever more tantalizing. Without a genetic test, it was impossible to determine whether a family member was affected by the disorder. The typical age of SCA1 onset corresponded perfectly to the period in an adult's life when he or she is considering marriage and children. If a family member reached 33 years of age and remained symptom-free, then it was unlikely he or she would develop ataxia. Otherwise, he or she risked passing the disorder to the next generation. On the advice of Dr. John, at-risk family members who had a parent with ataxia delayed having children or avoided conceiving altogether.
Dr. John's ataxia worsened to the point where he was unable to conduct his research. This infuriated him and made him determined to do everything he could to stay alive to focus on finding a cure. His spirits brightened when Henry's son Larry entered the University of Minnesota Medical College in 1958. Henry had remained unaffected by the disorder, so his children were at no risk of developing ataxia. Yet he and his children were closely tied to the disorder, because three of Henry's four siblings were affected. Antibiotics and new medical interventions kept Dr. John alive for longer than any other family member with the disorder; he eventually passed away at age 51 after fighting ataxia for 23 years.