In FD is a rare genetic disorder that impacts the nervous system and appears almost exclusively in the Ashkenazi Jewish population.
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A natural food supplement widely available in pharmacies and health stores – called phosphatidylserine – is made from beef, oysters and soy. Proven to improve cognition and slow memory loss, it’s taken by many older people suffering from memory impairment. Now a team headed by Prof. Gil Ast and Dr. Ron Bochner of Tel Aviv University’s department of human molecular genetics has discovered that the same supplement improves the functioning of genes involved in degenerative brain disorders, including Parkinson’s disease and Familial Dysautonomia (FD).
In FD, a rare genetic disorder that impacts the nervous system and appears almost exclusively in the Ashkenazi Jewish population, a genetic mutation prevents the brain from manufacturing healthy IKAP proteins – which likely have a hand in cell migration and aiding connections between nerves — leading to the early degeneration of neurons. When the supplement was applied to cells taken from FD patients, the gene function improved, and an elevation in the level of IKAP protein was observed, said Ast. These results were replicated in a second experiment that involved administering the supplement orally to mouse populations with FD.
The findings, which were recently published in the journal Human Molecular Genetics, are very encouraging, he added. “That we see such an effect on the brain – the most important organ in relation to this disease – shows that the supplement can pass through the blood-brain barrier even when administered orally and accumulate in sufficient amounts in the brain.”
Already approved for use as a supplement by the FDA, phosphatidylserine contains a molecule essential for transmitting signals between nerve cells in the brain. Ast and colleagues decided to test whether the same chemical, which is naturally synthesized in the body and known to boost memory capability, could impact the genetic mutation that leads to FD.
Researchers applied a supplement derived from oysters, provided by the Israeli company Enzymotec, to cells collected from FD patients. Noticing a robust effect on the gene, including a jump in the production of healthy IKAP proteins, they then tested the same supplement on mouse models of FD, engineered with the same genetic mutation that causes the disease in humans.
The mice received the supplement orally, every two days for a period of three months. Researchers then conducted extensive genetic testing to assess the results of the treatment.
“We found a significant increase of the protein in all the tissues of the body,” said Ast, including an eight-fold increase in the liver and 1.5-fold increase in the brain. “While the food supplement does not manufacture new nerve cells, it probably delays the death of existing ones,” he adds.
THAT THE supplement is able to improve conditions in the brain, even when given orally, is a significant finding, noted Ast. Most medications enter the body through the bloodstream, but are incapable of breaking through the barrier between the blood and the brain. In addition, the researchers say the supplement’s positive effects extend beyond the production of IKAP.
Not only did phosphatidylserine impact the gene associated with FD, but it also altered the level of a total of 2,400 other genes – hundreds of which have been connected to Parkinson’s in previous studies. The researchers believe that the supplement may have a beneficial impact on a number of degenerative diseases of the brain, concludes Prof. Ast, including a major potential for the development of new medications which would help tens of millions of people worldwide suffering from these devastating diseases.
GOOD PILLS TO QUIT SMOKING
Nicotine-replacement therapy drugs that have been licensed by the government have been shown to help smokers kick the habit, according to a new systematic review published in The Cochrane Library. The study, which is an overview of previous Cochrane reviews, supports taking smoking-cessation medications that are already widely licensed internationally and shows that another drug licensed in Russia could hold potential as an effective and affordable treatment.
In Europe and the US, the only medications currently licensed for smoking cessation are nicotinereplacement therapies (NRTs) such as nicotine patches and gums, the antidepressant bupropion and the drug varenicline, which blunts the effects of nicotine on nicotine receptors in the brain. In Russia and other parts of Eastern Europe cytisine, which is similar to varenicline, is also licensed for smoking cessation. Most of the medications are included in Israel’s basket of health services.
The authors combined the findings of existing Cochrane reviews on the subject, using all the available data from across the individual reviews. In total, they collected evidence from 267 studies, which together involved a total of 100,000 people. The studies covered a wide variety of licensed and unlicensed smoking cessation medications, comparing the treatments with placebo, and the three main treatments with each other. If a person stopped smoking for six months or longer, this was considered a successful attempt at quitting.
The three widely licensed medications and cytisine all improved smokers’ chances of quitting. The odds of quitting were about 80 percent higher with single NRT or bupropion than with placebo, and between two and three times higher with varenicline than with placebo.
However, Varenicline was about 50% more effective than any single formulation of NRT (patches, gum, sprays, lozenges and inhalers), but similar in efficacy to combining two types of NRT. Based on two recent trials, cytisine improved nearly four times the chances of quitting compared with placebo.
“This review provides strong evidence that the three main treatments – nicotine replacement therapy, bupropion and varenicline – can all help people to stop smoking,” said lead researcher Dr. Kate Cahill of the University of Oxford. “Although cytisine is not currently licensed for smoking cessation in most of the world, these data suggest it has potential as an effective and affordable therapy.”
The researchers also assessed the safety of different medications.
Bupropion, which is known to trigger occasional seizures in vulnerable people, did not lead to an increase in the rate of seizures when used for smoking cessation in its slow-release version.
Overall, NRT, bupropion and varenicline are considered low risk treatments, although the researchers say the results are currently less clearcut for varenicline.
“Further research may be warranted into the safety of varenicline,” said Cahill. “However, in the trials we looked at, we did not detect evidence of any increase in neuropsychiatric, heart or circulatory problems.”