What happens in fatal familial insomnia, exactly?

What is it?

Fatal familial insomnia (FFI) is a very rare genetic disease. The average age of onset is 50. Symptoms start as an increasing insomnia that eventually results in panic attacks, paranoia, and phobias. Then hallucinations and panic attacks become even more severe. Eventually the person is not able to sleep at all, which causes them to loose a lot of weight. Then they become demented and unresponsive, and after about 18 months of onset they die.

FFI is estimated to only affect about 100 people worldwide.

What causes it?

FFI is caused by a genetic mutation. The allele (specific version of a gene) that causes it is dominant, which means that you only need a copy from one of your parents to be affected. So, if a person with one FFI allele and one healthy allele would have children with a person with two healthy alleles, their children would have a 50% chance of having the disease. It’s extremely rare, but it’s also possible to get the disease if the gene mutates spontaneously in a sex cell or during the very first stages of human development.

What happens during it?

FFI is a prion disease. A prion is a protein that can be folded in several ways, and at least one of these ways has to be transmissible to other prion proteins. So, if you have many prion proteins on a cell membrane and one of them folds into the infectious form, it starts to cause other prion proteins to also fold in the same way, initiating a chain reaction.

Genes are the instructions of proteins. The gene mutation behind FFI causes a certain protein to be slightly different from normal. It is not exactly known why, but earlier in life this seems to cause no trouble: the disease onsets when a critical amount of these proteins have been converted into the infectious form and the misfolding starts to spread around the brain. This process leads to the death of nerve cells through apoptosis (the cells essentially kill themselves), although the mechanism of this is not known with certainty.

It is known that the normal form of the misfolded protein is necessary for normal sleep, and the progressive loss of the normal form is one of the factors leading to the insomnia. The hypothalamus is supposed to deactivate things like wakefulness and the activity of the neural pathways used to stimulate the systems we use when we are active. Another brain parts control how the hypothalamus does this. In FFI these controlling parts become damaged, and the hypothalamus starts to activate, not deactivate, these functions even when the patient tries to rest.

Although neurodegeneration sooner or later always results in death, it is unlikely that most FFI would die because of neural damage. Sleep deprivation can be very damaging: puppies die within 4-6 days of it, while rats die within a couple of weeks. It is probable that death in FFI results because the body simply can’t cope with the levels of sleep deprivation. That is why it is thought that intensive treatment of the symptoms might prolong survival, and there is anecdotal evidence that it might extend life by a year and also improve the quality of the remaining time.

How can it be treated?

Unfortunately, any attempts to find a cure for FFI have so far been unsuccessful. Sleeping pills might seem like a useful thing to try, but in fact they only make the situation worse. It is very much recommended that anyone with a risk of FFI would get tested for the gene before having children in order to stop the disease from passing on to future generations. Recent studies have suggested that a compound called doxycycline might be able to slow down or even reverse the progression of FFI, giving hope that a treatment may be available somewhere down the line.



Sources: https://en.wikipedia.org/wiki/Fatal_familial_insomnia, https://www.ncbi.nlm.nih.gov/pubmed/9669702, http://www.medscape.com/viewarticle/542963_2, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1781306/, https://en.wikipedia.org/wiki/Prion


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