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This is a story that is ultimately about love, but it's also about an unfathomable horror and two extraordinarily intelligent people.
In early 2010, a woman living in western Pennsylvania named Kamni Vallabh began experiencing problems with her vision. Several months later, she was confused and easily distracted , and she began having problems with her speech. All this was worrying to her newly-married, 25-year-old daughter Sonia, who had graduated from Harvard University's law school and was just beginning her law career.
By May, Mrs. Vallabh could no longer stand or bathe herself, and sleep was becoming impossible. In search of a diagnosis, Mrs. Vallabh's husband, a doctor, took her first to a local neurologist, then to the Cleveland Clinic, and finally to the famed Brigham and Women's Hospital in Boston.
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By October, Mrs. Vallabh was on life support, and knowing her wishes, her family decided to remove her from it. It was only at autopsy that a diagnosis was finally made: Fatal Familial Insomnia, so named because in some patients it completely eliminates the ability to sleep. Fatal Familial Insomnia is one of a family of human and animal diseases known as transmissible spongiform encephalopathies (TSEs), or prion diseases.
Like origami in the brain
Prions are abnormally folded proteins that clump together within the brain. Other TSEs include Creutzfeldt-Jakob disease, which kills an estimated 500 people per year in the U.S. Abnormally folded proteins can arise spontaneously, or else get into the human body by receiving a corneal transplant or a skin graft from an infected person, or by eating beef infected with the animal form of the disease called bovine spongiform encephalopathy (BSE).
BSE is also known as Mad Cow Disease, and there was an outbreak of it in cattle in Great Britain in 1986. By 1993, 120,000 British cattle were affected, and in May 1995, 19-year-old Britain Stephen Churchill became the first known victim of Creutzfeldt-Jakob Disease (vCJD) in that country.
By March 1996, Britain had 10 cases of vCJD in people aged 42-years-old or younger, and 4.5 million cows had been destroyed. In August 1996, a 20-year-old British vegetarian named Peter Hall died of vCJD which was thought to have been caused by him having eaten hamburgers as a child.
By July 1997, 21 Brits had died of vCJD, and in September 2001, the first outbreak of BSE began in Japan, followed in December 2003 by a case in the U.S. The U.S. Department of Agriculture (USDA) immediately eliminated sick cattle from the U.S. food supply, and they prohibited the eating of cow brain and spinal cord.
By January 2004, 143 people in Great Britain had been diagnosed with vCJD, and in the U.S., the USDA instituted new rules on the transportation of livestock across state lines.
One man refuses to give up
Prions were first encountered in 1954 when scientists examined The Fore people of Papua New Guinea. The Fore were experiencing an outbreak of what they called kuru, which means "to shake".
The scientists determined that whatever was causing kuru wasn't infectious in the typical sense, but that it might be related to The Fore's unusual tradition of eating their recent dead.
In 1972, a chemist at the University of California San Francisco named Stanley Prusiner began studying the sheep disease scrapie, so named due to the animals incessant scraping against fence posts, trees, and rocks alike.
Facing intense pressure from both the school and his colleagues, Prusiner persevered in his research and determined that scrapie replicated itself in a novel way without using any genetic material. Prusiner called what was causing scrapie a proteinaceous infectious particle, or prion, and in 1997 for his pioneering work, Prusiner was awarded the Nobel Prize in Medicine.
The Fatal Familial Insomnia that killed Kamni Vallabh is almost always inherited, and the onset of symptoms typically begins between the ages of 35 and 55. Fatal Familiar Insomnia symptoms include a lack of muscle coordination, difficulty walking, dementia, involuntary eye movements, blindness, and deafness. In other words, a true horror.
Fatal Familial Insomnia wasn't recognized until 1986, that's when a Venetian man suffering from worrying symptoms walked into the laboratory of a group of researchers at the University of Bologna in Italy. Before succumbing himself, the man described how over two centuries members of his family had died of a strange disease. The researchers published a paper describing the disease in the October 1986 issue of The New England Journal of Medicine.
In 2001, an American man suffering from the disease was able to describe its symptoms to his doctors before dying. He described feeling surrounded by both alive and dead loved ones, and that his consciousness seemed to have merged with that of the universe.
By 2014, 46-year-old Rebecca (Becky) Lockhart had already served for 16 years in Utah's House of Representatives. That year, she became the state's first female Speaker of the House. Then, just before Thanksgiving, Lockhart began experiencing sudden vertigo. By January 5, 2015, she could no longer speak or swallow, and she was diagnosed with Creutzfeldt-Jakob disease. Lockhart died just 10 days later, and as with 85% of cases, no genetic cause could be found.
Sonia Vallabh and Eric Minikel
Following Kamni Vallabh's funeral, Sonia Vallabh and her husband, Eric Minikel who had just finished his master's degree in urban planning at the Massachusetts Institute of Technology (MIT), returned to their lives in Boston.
Learning that Fatal Familial Insomnia was inherited, Sonia chose to be tested, and the results couldn't have been worse, she had inherited her mother's disease.
Instead of being crushed by the news, Sonia and Eric swung into action. As Sonia Vallabh told NPR in a June 2017 article about that time, she said, "We were finding our way toward a new normal, where this was something that we were going to have to live with and deal with and learn more about."
Both Sonia and Eric quit their jobs and they went back to school to study biology. Sonia found a job in a lab that was studying Huntington's Disease, another of the fatal brain diseases, while Eric brought his data analysis skills to a genetics lab.
By the fall of 2013, Vallabh and Minikel had applied to a Ph.D. program at Harvard University, and they applied to conduct research at the Broad Institute, a joint collaboration of Harvard University and MIT.
Vallabh and Minikel decided to focus their research on the protein in the brain that gives rise to prions called prion protein (PrP). It is encoded by the prion protein gene (PRNP) which is located on human chromosome 20. It is thought that all vertebrates have PrP within their brains and that it is floppy. That means it can spontaneously misfold into different shapes, causing its neighboring PrP to also misfold.
After meeting a fellow scientist named Jeff Carroll, who was researching his own disease, Huntington's, Vallabh and Minikel partnered with a pharmaceutical company called Ionis, which makes antisense oligonucleotides, or ASOs. These are strands of nucleic acids which are similar to DNA and RNA, and they can either eliminate or else enhance protein production.
Hurdles that Vallabh and Minikel faced on their way to a human trial using ASOs to reduce PrP production were the need to get approval from the U.S. Food and Drug Administration (FDA), the need to create a reliable way to measure PrP levels, proof that ASOs worked in mouse models, and a requirement that they set up a registry of human participants for their trial.
If that wasn't enough, the Minikels also needed to secure over one million dollars a year in funding in order to continue their research.
Rays of hope
As of January 2020, the Minikels had received approval from the FDA, they had over 200 people enrolled in their registry, and their research study to find a Fatal Familiar Insomnia cure was already over-enrolled, comprised of people either suffering from, or at risk of getting prion disease.
In 2016, after undergoing In Vitro Fertilization with Preimplantation Genetic Diagnosis, Vallabh and Minikel had a baby daughter who is free of the disease that killed her grandmother and is threatening the life of her mother. In the spring of 2019, both Sonia and Eric received their Ph.D.s. in Biological and Biomedical Sciences from Harvard.
The Minkels have set up a charity called the Prion Alliance, a 501(c)(3) non-profit organization, to solicit funds for their work.