Anxieties about liver fibrosis is a valid concern for all alcoholics, for currently there is no cure for this progressive disease. A much awaited research by doctor George Kunos of National Institute of Health (NIH) was recently published, which might just prove to be a gleam of hope for all those worried and lead us to a therapy for liver fibrosis. The team has reformulated the reverse agonist rimonabant which is reported to limit the progression of liver fibrosis in mice.
Liver fibrosis is the buildup of scar tissue accompanied by an overabundance of extracellular proteins in the liver. Because scar tissues are not able to perform normal liver tissue function, it increases the stress on the remaining tissues of the liver, ever increasing the area covered by scar tissue. The US Centers of Disease Control and Prevention (CDC) states that per year the number of deaths caused by liver diseases induced by alcohol are 18,146.
The current investigation was praised by Director of National Institute on Alcohol Abuse and Alcoholism (NIAAA) George F Koob, “This study represents an important step towards an effective treatment for liver fibrosis.”
Rimonabant was previously only able to target its cannabinoid type 1 receptor and that too in a haphazard manner, since the original molecule was able to cross the blood brain barrier and activate the cannabinoid type 1 receptors in the brain as well. This messy mode of action of rimonabant often gave serious mental side effects to the patient. Furthermore, since the conventional drug did not interact with the iNOS enzyme (the enzyme involved in the progression of fibrosis), its potency was very questionable.
The study published in the journal JCI Insights was conducted on mice. Scientists designed a substitute rimonabant that did not have the capability to cross the blood brain barrier, hence it did not activate the cannabinoid type 1 receptors in the brain of mice. Additionally, researchers added the inducible nitric oxide synthase (iNIC) inhibitor group to the molecule. This auxiliary part disassociates from the overall therapeutic compound once in the liver and goes on to inhibit the iNOS by attaching to it.
As of yet, medical professionals are using drugs that aren’t dual purpose. Currently employed drugs for fibrosis follow the one-drug-for-one-target trend. The group at NIH argues that this kind of traditional approach is ineffective for fibrosis because the disease is a multifactorial occurrence and involves several different pathways.
For that reason, the team under the guidance of George Kunos, the lead scientist, has attempted the multi-target approach. They are employing a single molecule which hits pathways involved in the biogenesis fibrosis at several key junctures. But due to fact the drug is so radical, scientists will have to be extra wary of possible side effects. Although the drug has passed through the initial tests and has not shown any genotoxicity or association with some unwanted receptors, Kunos stated that it will have to be further tested on animal models before it can be employed in clinical trials involving humans.
Liver Fibrosis is the gateway to several disorders of the liver. Primarily, fibrosis leads to cirrhosis, a condition where the scar tissuehas spread so extensively in the liver that the organ is unable to perform its function. The outcome can escalate up to hepatocellular carcinoma. Because the disease is so progressive, in several circumstances the patient has to get a transplant.
As there is no proper treatment for liver fibrosis yet, one should be cautious of the amount of alcohol consumed by him or her, which according to the UK government’s guidelines are same for both men and women. However, the Dietary Guidelines for Americans suggests that men can have up to two drinks per day while the safe amount for women is one drink a day. Of course they explicitly mention that if you don’t drink at all, you shouldn’t consider starting to drink.
The possibilities this drug can bring are truly reassuring. If it transforms into a therapy, then several patients can reap the benefits of this research and stop the progression of their liver fibrosis. However, it would be unwise to start drinking in excess while being reassured that one could simply medicate their liver later on. This research is still in the pipeline and although the initial signs are positive, they in no sense mean the researched compound will indisputably transform to a commercially available remedy.