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What is it like to lose the ability to sleep forever 

Stories of people with fatal insomnia – a rare incurable disease that leads to death in 100% of cases.

American Sonya Vallab and her husband Eric in 2017. The last few years, the couple are looking for a cure for fatal family insomnia, which is transmitted to the girl from her mother. Photo NRP

For more than 40 years, the scientific community has been seeking a cure for fatal familial insomnia, a genetic disease that, as a result of a mutation, destroys sleep function and leads to painful death. This is a rare affliction, about which almost nothing is known, which has become a “curse” for dozens of affected families. The disease forces us to give up the birth of children, to hide the truth about ourselves and to live in the hope that the disease will come when most of the person’s life is already behind. And only a few are trying to find a cure.

Family burden

In 1983, a 52-year-old resident of Venice named Silvano (last name not disclosed at the request of relatives) put on one of his tuxedos and went to a festive event in the city. There, as head of the family, he courted, cheered and danced with his mother. She needed this – only recently an elderly woman had survived the death of two daughters. Silvano was glad to make her happy, although he was annoyed that he was somehow sweating excessively. Having seized the moment, the Italian went to the toilet and looked in the mirror – he immediately noticed how his pupils abnormally narrowed. And immediately understood everything.

The sisters Silvano did not die accidentally, but after fighting with long insomnia. It did not last a day, not two or a week, but months, until finally the girls ’body gave up. The bodies of their relatives, right down to the distant ancestors, surrendered in the same way. Like Silvano, in the early stages, the girls suffered from sweating and severe constriction of the pupils.

In the family, this disease was called a “curse”, and never told about it to strangers. Silvano knew about this, but decided that he could not continue like this. A few days later he came to the neurologists of the University of Bologna, the oldest in Europe, and told everything he knew about the mysterious illness. The doctors assured the man that he would be helped, but Silvano waved off, saying that he could not be saved. He just wanted to help sort out the disease and find a cure.

Silvano after the start of the examination by doctors. Frame from research records

The Italian began to regularly come to the university for examinations and tests that were recorded on camera. He usually slept for five to seven hours at night and dozed for about 30 minutes after lunch, but after the onset of symptoms of the disease, insomnia gradually rolled over him. For the first two months he could sleep two to three hours a day, and on the third he slept no more than an hour. But even when the man was awake, he had dreams: they involuntarily forced him to carry out a military salute, lying on the bed, or urged him to pull the buttons of his pajamas.

Month after month, the man became worse: he had regular tremor in his hands, delirium, problems with speech, inability to concentrate, difficulty swallowing and urinating. By the fourth and fifth months, he had ceased to sleep, instead falling into hypnagogy, an intermediate state between reality and sleep. Something similar is observed while driving behind the wheel, when a tired sleep wave suddenly rolls over to a tired driver, but due to driving, he also suddenly wakes up.

At about the seventh to eighth months, Silvano had short episodes of emotional arousal, accompanied by feelings of anxiety, fear, and panic. He barely moved on his own and suffered from amnesia. His body temperature was 38 ° C, the heart rate reached one hundred beats per minute.

[perfectpullquote align=”full” bordertop=”false” cite=”” link=”” color=”” class=”” size=””]“I’ll die in a few months. For you, this is a rare chance to find out the reason for the curse of my family, ”Silvano told his doctor.[/perfectpullquote]

He was right – in July 1984, the ninth month after the first symptoms appeared, the Italian died. In the hope that his death was not in vain, he tentatively bequeathed his body to the university. The postmortem autopsy and examination of the brain revealed almost no abnormalities, except for one sponge-like formation, near the central part of the brain. At that time, doctors began to guess what ailment Silvano had encountered.

Age-old heritage

Fatal familial insomnia (Fatal familial insomnia – FFI) – as the Italian doctor Ignazio Reuter called the disease discovered by him in 1979. This young specialist was married to a relative, Silvano, and watched his sisters die. After that, he decided to find out the truth about the origin of the disease and, thanks to his wife, went to the old psychiatric hospital of the island of San Servolo in Venice.

The records of this distant ancestor Silvano were still kept in the archives of this institution, which were sent for treatment due to symptoms suspiciously similar to those of FFI. Data on the quality of the treatment of a man has not been preserved, but perhaps the priests leading the clinic suspected him of being possessed. At least this has happened before.

In 2006, the American science journalist D.T. Max (DT Max) published a book entitled “ The Family That Could Not Fall Asleep ”, which tells about Silvano and his ancestors. The work is based on interviews with doctors, relatives and data archives, and performed at the intersection of a literary detective and a scientific essay.

[perfectpullquote align=”full” bordertop=”false” cite=”” link=”” color=”” class=”” size=””]In the book, the author, with the help of Reuter, traced the Silvano family to the 1760s – and all these years, a rare insomnia disease has been present in family life.[/perfectpullquote]

For example, at the beginning of the 19th century, a supposed relative of Silvano, 10-year-old Kostante, was tormented by a certain ailment. He behaved strangely, did not sleep at night and saw hallucinations. In an attempt to cure his son, the boy’s father asked to conduct an exorcism rite over him, but no matter how the priest tried, the disease did not recede, and Kostante soon died. Later the father of the child also died, and years later his brother also after a long insomnia.

It is not known where the FFI “patient zero” comes from. It is believed that this is a native of Egypt, who has lived for more than 19 years in the Netherlands, but there is no certainty about this information. In the book The Family That Could Not Fall Asleep, the author focused on the activity of the disease in Venice. This may partly explain why many cases of FFI are recorded in America – in the 1890-1920s, millions of Italians moved to the United States and Canada, as well as to Latin America and South America.

Medical look at FFI

“The mystery of how this disease, like a snake, passed unnoticed through generations,” said the discoverer of fatal family insomnia, Ignazio Reuter. He found that FFI is a rare genetic disorder related to prion diseases. This is a special class of infectious agents that concentrate near the center of the brain – the thalamus, which is responsible for the expression of emotions and the process of sleep.

The closest prion analogue of FFI is “mad cow disease” that destroys brain cells. With Silvano and his ancestors, the same thing happened: prions gradually killed brain cells in the thalamus, and the further the process went, the less infected could sleep. There is no medication or sleeping pill that can stop the process. If you give the patient sedatives, he will not fall asleep, but will fall into some kind of coma analogue, during which time he will not recover energy.

Since both parents pass on their genes to a newborn, the suffering FFI has a 50% chance of transmitting the disease to the child. “You had 14 children of the same generation. Six or seven of them died from this disease, ” said D.T. Max. There is also a second type of disease called “sporadic”. About this form almost nothing is known, except that it is acquired not by inheritance, but in some other way. For 2016 (more recent data are not available) , only 24 cases of fatal familial insomnia of a sporadic species were recorded for the entire time.

The documentary of the American channel ABC about fatal family insomniaAccording to the author of the book The Family That Could Not Sleep, it is reliably known about 40 families suffering from a rare disease. The researcher clarified that if you extrapolate official calculations, there are about 200 families with ailment in the world. It is difficult to say precisely, no regular statistics on the diseased are kept, nothing is known about the spread of FFI in Russia.

In most cases, the symptoms of FFI appear after 50 years, before this does not impart itself. In more rare cases, adolescents and people up to 30 years old are affected by the disease – this has almost no effect on life expectancy, mostly death occurs in nine or twelve months, or earlier.

Despite the fact that current technologies allow to pass the FFI gene test in advance, families with this disease often hide the truth about it. In 2017, an American family consisting of mother, daughter, and son told their press stories of coexistence with illness. After the death of a spouse and father named Rick White, relatives decided to stop hushing up the details of their illness and pass a test of predisposition to it. This required moral effort – on the one hand, the relatives wanted to find out if they had the FFI gene, and on the other hand, they preferred ignorance. Often, family members with the FFI gene prefer the second option.

The results of the analysis did not reveal the disease in the son and daughter of the White, which means that their potential children also avoided fate. For the clan it is a celebration, but bitter, because before that at least 16 relatives had died from FFI. In addition, the disease can still go to the children of other family members. “If I knew about the disease, I wouldn’t give birth to children, because this is not what you would like to reward them with,” says the late Rick White’s aunt, Judy Peterson. She can be understood – until the death of her nephew as a result of the illness, she lost her husband, son and daughter.

Hope for medicine

In 2011, the American Sonya Vallab (Sonia Vallabh) faced two difficult events with a difference of several weeks: first, her 51-year-old mother died after a hard struggle with FFI, and then the girl was told that she had the gene for this disease. At that time, the 27-year-old Harvard law graduate worked as a legal advisor, and her husband Eric was in the transportation industry. Their careers have just begun, but the revealed truth made it clear that they will have to leave their former life behind.

The girl saw what happened to her mother and did not plan to repeat her fate. She took up biology and volunteered at the Massachusetts General Hospital to learn more about the intricacies of medicine. In 2014, Eric also abandoned his former career and joined his wife’s research. Together, they founded the non-profit organization Prion Alliance to raise funds for the search for drugs and started a blog where they talk about their path “from patients to scientists”.

Sonya and Eric. Photo of Broad Research Institute, which collaborates with Harvard University and Massachusetts Institute of Technology

The couple conducts research in conjunction with the doctors at Harvard Medical School, but focused on finding a cure not from FFI, but from all prion diseases that thousands of people suffer from. According to scientists, the discoveries of recent years help to understand more about rare ailments, but to create drugs you need to experiment, and for experiments you need more money and volunteers. However, finding people with prion diseases like the Italian Silvano is difficult and time consuming.

Sonya and Eric are negotiating with pharmaceutical companies about future experiments on volunteers, but for now this is a foggy road with no definite prospects. Even if you create the right drug and give it to people with a mutated mutation gene, how do you know if it works? Offer a person to wait and hope that the disease does not manifest? Too unethical and risky option, they believe the spouse.

In the summer of 2018, Sonia announced in her blog that the spouses had agreed to cooperate with California-based pharmaceutical company Ionis Pharmaceuticals. She specializes in research in the field of antisense therapy – this treatment method is based on stopping the synthesis of the protein involved in the development of the disease. Roughly speaking, this technique may allow point-to-point slowing down or stopping the development of FFI.

[perfectpullquote align=”full” bordertop=”false” cite=”” link=”” color=”” class=”” size=””]“For the first time, I am optimistic about a specific therapeutic strategy. There is a possibility that an antisense can cure a disease in our age, ”Sonia believes.[/perfectpullquote]

The scientific journal MIT Technology Review acknowledged that this medical theory has a chance, thanks also to the current technologies of gene therapy and the editing of the CRISPR gene. In the end, the potential of these funds has not yet been disclosed. “At least on paper, now it’s really possible to take some kind of genetic defect and quickly outline an antidote,” reads the MIT article.

According to Sonya, she is ready to experience the experimental cure for prion disease as soon as it becomes possible. It is unclear whether this will happen in the next decade or in a year, but the girl confidently says that research is moving much faster than expected.

In 2017, 33-year-old Vallab had a daughter with a negative analysis for the presence of the FFI gene. The couple hopes that when the daughter grows up, she will be able to see the prosperous old age of the mother. If you start from the common age of FFI, after 50 years, Sonya has a little more than 15 years left in search of a cure.

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