miRNA 122 assessments for liver toxicity
We now provide a microRNA122 measurement service; originally designed for application in primary care, is now being launched for toxicity screening during experimental, preclinical and clinical phases of therapeutic development. MicroRNA122 is highly abundant and specific to all vertebrates; its nucleic acid sequence is completely conserved between species, highlighting its evolutionary significance and translational application along the healthcare value chain throughout the species used. Within the liver its expression accounts for greater than 70% of the total microRNAs present with a high level of tissue specific expression; miRNA122 expression in the liver is at least 1000 time greater than in any other tissues.
Serum microRNA122 variations have been identified as the biomarker for many types of liver damage from many sources; Some studies have also revealed that serum microRNA122 can be used to differentiate between different types of liver damage that has occurred, which we summarise below.
- Serum levels of microRNA122 are elevated in patients experiencing Drug Induced Liver Injury, and these levels were higher than with other forms of acute liver damage.
- microRNA122 levels correlate with disease severity in patients with non-alcoholic fatty liver disease.
- In a preclinical mouse model system, the circulating form of microRNA122, could be used to not only detect liver damage, but also to differentiate between causes: drug-induced injury led to microRNA122 being found in the protein fraction of the mouse serum, while alcohol and inflammation-induced liver damage led to circulation of microRNA122 in exosomes.
DILI is estimated to have an annual incidence of 10 to 15 per 10,000 to 100,000 persons exposed to prescription medications. This makes it costly in terms of not only its toll on humans, but also healthcare expenditures. This prevalence is expected to increase with the widespread use of dietary supplements. Of the 2,000 cases of acute liver failure (ALF) that occur in the U.S. each year, medications account for >50%, with 37% of cases attributable to APAP and 13% attributable to idiosyncratic adverse drug reactions.” See more at: uspharmacist.com More recently drug induced liver damage has resulted in the EMA restricting a novel therapy : multiple-sclerosis-research.blogspot.com
As polypharmacy is commonplace in many patient populations, the risk of dangerous Drug-Drug-Interactions (DDI) is high. For example, in the general population, DDIs have been considered responsible for 20%-30% of all adverse drug reactions and account for about 10% of visits to emergency departments. “In hospitalized patients, they represent 3%-5% of medication errors and have been estimated to be the cause of death in 4% of cancer patients, to whom drugs are frequently administered at or close to the maximum tolerated dose. Both transporter- and enzyme-mediated DDIs can significantly alter drug pharmacokinetics and have therefore the potential to affect the therapeutic efficacy or toxicity of drugs.” Palatini et al, World J Gastroenterol 2016 January 21; 22(3): 1260-1278.
- The EMA, has considered microRNA122 as a promising marker candidate for DILI.
- Genechron’s microRNA122 measurement services, requires sending low volumes of serum to our measurement laboratories.
- The turn-around time is approximately one week
Our products during therapeutics development