Can you imagine never being able to sleep, thus denying your body and brain the chance to rejuvenate? It’s a scary thought, but sadly it’s what sufferers of a rare condition known as Fatal Familial Insomnia (FFI) have to go through until it eventually kills them. This mysterious genetic disease affects less than one in 10 million people worldwide and has no treatment or cure.

According to a BBC report, Fatal Familial Insomina is almost unheard of because most families who carry the gene have chosen to remain silent about it. It makes sense, given that most people might not want their children to know about the cruel fate that awaits them. There’s no way to predict when or which family members FFI will strike, and since there’s no cure, they tend to avoid talking about it for fear of tempting fate.

In recent times, however, a few families have chosen to open up about the illness that has plagued their genealogical tree. Like that of Silvano, a Venetian man who lost his father and two sisters to the fatal illness and succumbed to it himself in the 1980s, at age 53. But he left his brain to science in the hope that doctors might discover more about the condition. The family’s story became the subject of the book The Family Who Couldn’t Sleep, written by DT Max, who managed to trace the disease back to a Venetian doctor in the late 18th century.

Photo via jpmsonline

The matter was further investigated by two doctors – Ignazio Roiter, the husband of Silvano’s niece, and his friend Pietro Cortelli. As the BBC reports, “Although their efforts could do nothing to save Silvano or two other family members who would succumb shortly afterwards, extensive brain testing eventually found the culprit: a misshapen protein in the brain called a prion, caused by a tiny genetic mutation. For some reason it is only at middle age that the prions begin to proliferate wildly, collecting in pockets that poison the neurons.”

With this discovery, FFI was classified as a relative of two other prion diseases that were gaining interest at the time – Creutzfeldt-Jakob disease (CJD) and Mad Cow Disease. Today, after several years of research, scientists are able to explain that the prion “orchestrates all our ‘autonomic’ responses to the environment.” So when it breaks down, chaos descends on the brain, resulting in symptoms like profuse sweating, shrunken pupils, impotence, constipation, and permanent insomnia.

Not only are the people suffering from FFI unable to sleep, they also get into a sort of mindless stupor where they are not really asleep but not aware of their surroundings either. According to Cortelli, this resembles the REM stage that occurs during deep sleep. In some cases, he noticed that patients were acting out their dreams – like this one woman, Teresa, who would constantly mimic the action of combing hair. She had been a hairdresser before her diagnosis.

Photo: video caption

While most FFI sufferers die soon after being struck by the disease due to rapid physical and mental degradation, the BBC presents the case of a remarkable American man in the 1990s who refused to give in so easily, and instead tried to fight his fate. Daniel (named changed to protect the family’s privacy) carried the FFI mutation, but instead of simply waiting to die, he tried as many treatments as possible, no matter how outrageous they seemed. He took vitamin supplements, exercised regularly to improve his general fitness, and even took anesthetics like ketamine and nitrous oxide.

Sleep medicines like diazepam helped him get 15-minute naps, but it wasn’t enough. So he bought a sensory deprivation tank, filled it with warm salt water, and floated in it until his body eventually drifted off into a blissful four-and-a-half hours of solid sleep. The weird thing was that when he woke up he suffered terrible hallucinations that left him unsure if he was dead or alive. Daniel struggled for a few more years, trying more serious treatments like electroconvulsive therapy that would knock him out for a short while. Unfortunately, the aggressive approach gave him terrible amnesia. Despite his valiant struggle, in the end he succumbed to FFI. He did live years longer than expected though, which led experts to believe that there could be other measures that might extend the life of patients with FFI.  “It at least opens the possibility to say that there is something we can do,” Cortelli said.

Meanwhile in Venetia, Roiter and his colleagues believe they might actually be close to discovering a cure for FFI. Last year, they announced a clinical trial of a new drug called doxycycline, which seems to be able to stop the prions sticking together in clumps. They had good reason to believe that the drug could prevent the prions from amassing in people who are at a risk of FFI. “It might delay or completely disrupt the development of the disease,” explained Gianluigi Forloni, who is helping to lead the project at the Mario Negri Institute of Pharmacological Research in Milan.

Photo: Neurology.com

There is, however, one challenge in testing out the drug – it involves genetically testing members of the current generation of Silvano’s family, to see who might be carrying the mutation. Most of them, however, do not want to know their test results because of the fear and hopelessness that would cloud the rest of their short lives. So the trial will also provide a sham treatment to an additional 15 members who are not at risk of FFI. The trial will continue to study the subjects over the next decade – if over six manage to escape the disease by then, the trial will be considered a success.

Doctors like Cortelli are skeptical about the trial for two reasons. One, because the drug may have side effects on some of the subjects, actually giving away their diagnosis and causing them unnecessary distress. And even if there are survivors at the end of the trial period, it wouldn’t necessarily indicate that the drug was successful. Those few individuals might just have been lucky, given that the gene is known to remain dormant in some people until they are in their 80s. But Silvano’s family is willing to take these risks, because they finally have a fighting chance of liberation from the curse that has plagued their DNA for generations.

Another startling case of FFI in a pair of young siblings from Queensland, Australia, was recently covered on 60 Minutes. Hayley and Lachlan Webb, who are 30 and 28 respectively, first became aware of the disease in their early teens, when their grandmother became ill. “In my early teens I remember becoming aware of it, aware we had this family curse,” said Hayley, a Channel Nine news reporter.

Photo: 9News

“My grandma started getting sick and dying. Her eyesight went, she had signs of dementia, she was hallucinating and couldn’t talk. Eventually she was diagnosed with FFI and that was the first time the family even knew that FFI existed.” Their mother later developed symptoms in 2011, suffering severe hallucinations, and eventually passed away a mere six months later.

The siblings have now been diagnosed with the defective gene, but they have no idea if, when, or how the disease may strike. “My aunty passed away at 42, my mum passed away at 61, my grandmother passed away at 69, mum’s brother died at 20. We’re just hoping we’re not one of the young ones,” Hayley said. “It could happen tomorrow but until we’re in that danger zone we probably have a good 10 years up our sleeve and I am praying that there is a cure between now and then.”

“I don’t want to sit here while the sands through our hourglass pass waiting for it to trigger and for me to cark it,” added Hayley, who along with her brother is taking part in a study at the University of California that is attempting to find a remedy. “I want information, I want answers and I want a bloody cure.”

Just knowing that you are carrying the gene of this terrifying condition must be almost unbearable. Laying down in bed and wondering if this is the night you stop sleeping forever… Simply brutal!