TAU breakthrough in familial dysautonomia
The mechanism that causes the death of neurons in familial dysautonomia – a rare genetic disease of the autonomic nervous system more prevalent among Ashkenazi Jews – has been discovered by researchers at Tel Aviv University.
The team has already proposed a first treatment of its kind – a widely available food additive – for the condition, which is carried by one in 30 Jews of European origin.
The breakthrough could also slow other severe neurodegenerative diseases such as Alzheimer’s, Parkinson’s, Huntington’s and amyotrophic lateral sclerosis (ALS). The study was just published in the open-access journal PloS.
Doctoral student Shiran Naftalberg-Blonder, Prof. Eran Perlson and Prof. Gil Ast of TAU’s Sackler Faculty of Medicine carried out the research.
Familial dysautonomia affects the development and survival of certain nerve involuntary actions such as digestion, breathing, production of tears and the regulation of blood pressure and body temperature.
It also affects the sensory nervous system, which controls activities related to the senses, such as taste and the perception of pain, heat and cold.
The team suggested that the food additive called phosphatidylserine could apparently halt the advance of other horrible neurodegenerative diseases, such as Alzheimer’s, Parkinson’s, Huntington’s and ALS.
They found that the additive – which is even sold on the Internet – boosts the normal activity of the defective gene.
“We managed to show that the additive causes the body to synthesize the two enzymes that glue and separate. As a result, the neural highways are more stable, at a level closer to healthy neurons,” said Ast.
But Ast warned that he does not want to give false hopes to people suffering from those other diseases, as those diseases are more complicated than dysautonomia. “Most of the existing drugs at this point and most of those that will soon be marketed only slow disease. I believe [however] that phosphatidylserine will slow the degeneration of the neurons of those diseases, too. While it has worked in mice, it has not yet been used clinically in humans.”
Problems related to this disorder first appear in infants who show poor muscle tone (hypotonia), feeding difficulties, poor growth, lack of tears, frequent lung infections and difficulty maintaining stable body temperature. Older infants and young children with familial dysautonomia may hold their breath for prolonged periods of time, which may cause a bluish appearance of the skin or lips or fainting; this breath-holding behavior usually stops by age six. Developmental milestones, such as walking and speech, are usually delayed, although some affected individuals show no signs of developmental delay.
In addition to being carried by many Ashkenazi Jews in general, it is carried by one in 19 Ashkenazi Jews of Polish origin.
“All the cells in the body are like highways with trucks carrying goods along them,” said Ast. “The peripheral nerves contain the longest ‘highway system’ in the body, a two-way street a meter long that is located on the two sides of the spinal cord. Its job is to receive all data from the neurons in the body and send it for concentrated processing in the brain. Thirty years ago, it was shown that this mass of neurons degenerates in patients with familial dysautonomia.”
The “highways” are always being built and produce two enzymes, one that “glues” the alpha type and beta type of a substance together in the neurons. The researchers showed that one enzyme “unsticks” the alpha and beta types, while the other sticks them together. The enzyme that unsticks the glue is expressed by a surplus of neurons in mice sick with dysautonomia.