Carbamazepine Reduces Hepatic Fibrosis.....

We know that Carbamazepine (CBZ see structure), is an  anticonvulsant and mood stabilizing drug used primarily in the treatment of epilepsy and bipolar disorder, as well as trigeminal neuralgia. It is also used off-label for a variety of indications, including attention-deficit hyperactivity disorder (ADHD), schizophrenia, phantom limb syndrome, paroxysmal extreme pain disorder, and post-traumatic stress disorder.

Now researchers from University of Pittsburgh School of Medicine, have come up with interesting finding about this drug, i.e., the liver scarring of α1-antitrypsin (AT) deficiency, the most common genetic cause for which children undergo liver transplantation, might be reversed or prevented with carbamazepine.  The disease, which affects 1 in 3,000 live births, a gene mutation leads to an abnormal protein, dubbed ATZ, that unlike its normal counterpart is prone to aggregation. As per the claim by the researchers these aggregates of ATZ accumulate in the liver cells and eventually lead to scarring, or fibrosis, of the organ and set the stage for tumor development. The disease sometimes doesn't show itself until adulthood, when the liver starts to fail due to cirrhosis or cancer.

Encouraged by the fact that carbamazepine could enhance a natural cellular pathway called autophagy  or self-digestion, researchers thought that  it might be able to rid the cells of the toxic aggregated ATZ. For the study researchers treated an ATZ cell line with carbamazepine. They found that carbamazepine did indeed cause a marked decrease in ATZ because the abnormal proteins were degraded more quickly via autophagy, and so they did another experiment in a mouse model of AT deficiency.

The most amazing finding,  as per the claim by the researchers is  that the drug reversed the fibrosis in the livers of the mice and after two weeks of treatment the liver tissue resembled that of a healthy mouse...

The ability of carbamazepine and drugs like it to "soup up" the cell's autophagy machinery might have value in other disorders ― such as Alzheimer's disease, Huntington's disease and Parkinsonism ― that are thought to be caused by toxic effects of protein clumping in the brain. Dr. Perlmutter and his colleagues are now exploring these possibilities in preclinical studies. ....

Ref : http://www.sciencemag.org/cgi/content/abstract/science.1190354v1

Once-a-day epilepsy drug may prevent seizures as well as twice-a-day drug

In continuation of my update on Carbamazepine (CBZ)

A new study suggests that an epilepsy drug that can be taken once a day may control seizures as well as a drug that must be taken twice a day, according to a preliminary study released today that will be presented at the American Academy of Neurology's 68th Annual Meeting in Vancouver, Canada, April 15 to 21, 2016.

The study compared the once-a-day drug eslicarbazepine acetate to the twice-daily drug carbamazepine for people newly diagnosed with partial seizures, which start in one area of the brain.

"Seizure control is crucial," said study author Elinor Ben-Menachem, MD, of Gothenburg University in Gothenburg, Sweden, and a member of the American Academy of Neurology. "A once-a-day drug may help people stick to their medication schedule." For the study, 815 people newly diagnosed with partial seizures received either eslicarbazepine or carbamazepine for about six months. Participants started the study at the lowest of three dosing levels. Those who had a seizure at the lowest level were then moved up to the second dosing level. If they had another seizure, they received the highest dosing level.

A total of 71 percent of those taking eslicarbazepine and 76 percent of those taking carbamazepine were seizure-free after six months. After one year, 65 percent of those taking the once-daily drug were seizure-free compared to 70 percent of those taking the twice-daily drug.

The study was what is called a non-inferiority study, which is designed to show that a new treatment is not clinically worse than an existing treatment. According to the study design, eslicarbazepine would be considered "non-inferior" if the difference in seizure-free rate between the two drugs was 12 percent or lower. At six months, the difference was 4 percent. At one year, the difference was 5 percent.

"Memory issues, fatigue, or a complicated medication schedule can all interfere with a person taking their seizure-control medications on a regular basis so having a once-daily option for patients, especially when they are newly diagnosed and still learning to manage the disease, may be beneficial," said Ben-Menachem. "The hope is that these results may also give doctors more options to better tailor treatments for people with epilepsy."

Once-a-day epilepsy drug may prevent seizures as well as twice-a-day drug