Hereditary hearing loss is a hearing loss that is passed on from parents to children due to a genetic defect. The resulting hearing loss may or may not be present at birth. For some, it is an indicator of possible hearing problems later on in life. For others, it can be immediate and accompany other conditions such as blindness or speech problems. People with hereditary hearing loss may display difficulties with speech and balance or the ability to hear by itself. The onset varies between individuals, as does the severity of the hearing loss. A new study is suggesting that the anti-malarial drug artemisinin might be a possible solution to genetic hearing loss.
The study is supplying evidence that may be of tremendous benefit to those with genetic or hereditary hearing loss. Using research conducted with a zebrafish model, the researchers found that the anti-malarial drug artemisinin could be a solution to hereditary hearing loss. Proper hearing relies on proteins reaching sensory cells in the inner ear. If mutations in the protein exist, they fail to reach the membranes that are essential for hearing and balance. These mutations present themselves in certain types of hereditary hearing loss. For the research, genetically engineered zebrafish with human versions of the mutant protein experienced restored hearing and balance from artemisinin.
The team has been working on this mutant protein for some time now, aware that the mutant protein fails to influence the cell membrane, except in patients with the mutation who are born able to hear. The team felt that a portion of mutant protein must enter the cell membranes in the inner ear. From this point, the team examined the transportation process of the mutant protein. Normal human clarin1 was given to a portion of the fish to complete the investigation, while the other group received mutant clarin1.
The team was able to locate the unusual cellular paths. They chased human clarin1 moving through the zebrafish hair cells utilizing fluorescent markers to track human clarin1. The mutant clarin1 gets to the cell membrane via proteins and trafficking mechanisms within the cell, customarily used by misfolded proteins fixed in certain cellular compartments. The investigators noted that the mutant clarin1 was trapped within the tubules of the cells. Alagramam’s team gathered that if this protein were free, there customarily be a therapeutic benefit. They tested two drugs to target this problem. The two drugs included thapsigargin, an anti-cancer drug, and artemisinin, an anti-malarial drug.
Both drugs released the trapped protein and allowed clarin1 levels to rise in the membrane, with the artemisinin being the more effective of the two. The drug even enhanced the hearing and balance in the treated fish, as compared to the untreated fish. Zebrafish must be capable of normal swimming to survive. This normal swimming is dependent upon balance and the ability to detect water movement. The rates of survival for the zebrafish with the mutant clarin1 improved from five percent to 45 percent after being treated with artemisinin. The research team wishes to continue studying the clarin1 mutation in a mouse model and then possibly move on to clinical trials.