Big things come in small packages, and Dr. Hongsik Cho is very familiar with this phenomenon. When we first introduced Dr. Cho in August 2016, he was beginning work on his 2-year Arthritis Foundation-funded project, “A Novel Method of Detecting and Treating Early PTOA Using Smart Nanosome”. He and his team are studying two things: a new drug and a new drug delivery system. The drug, called TPCA-1, works to prevent inflammation caused by post-traumatic osteoarthritis (PTOA). The drug delivery system uses small packets called nanosomes that contain TPCA-1 and a fluorescent dye that illuminates the nanosomes’ path once injected into mice.
The first goal of the study is to find a way to provide early diagnosis of PTOA. Dr. Cho explained that one of the problems with treating PTOA is identifying damaged tissue in affected cartilage early. Lesions can be too small to detect. But Dr. Cho and his team have found a way to use nanosomes to diagnose PTOA at its beginning.
Dr. Cho says that healthy cartilage contains smooth collagen without any shown areas of bonded DNA. When collagen is damaged, these areas are unhidden and the surface of cartilage erodes. The team has developed a binding agent that is attracted to damaged collagen in cartilage. The binding agent combines with the fluorescent dye in the nanosome, and together they find the damaged collagen and can identify even the smallest lesions. The nanosomes target the injury with the binding agent and mark the injury with fluorescent dye.
“At the time when the first lesion forms after an injury,” Dr. Cho explained, “the lesion may not be detectable by normal means. But the pathways that cause cartilage degeneration are already beginning.”
Dr. Cho and his team have found that mechanical stress on a joint, like with PTOA, can cause a chemical domino-effect (or pathway) of events leading to cartilage degeneration. When the collagen is affected and the cartilage is injured, these pathways occur. The TPCA-1 drug is designed to block the inflammatory pathway caused by an injury to cartilage. However, TPCA-1 can have unwanted side effects when used in high doses and/or over long periods of time. By using a system of targeted nanosomes carrying TPCA-1, the team can control the drug concentration and how many times and how often the drug is delivered.
The study’s second and third goals are finding a way to make measurements in individual joints to track disease progression and determining how effective the drug treatment is. The project is in this stage. The team has detected OA in the mice they are treating with the targeted delivery system of TPCA-1. During the next 6 months, they will monitor the mice, measure lesions and OA progression while looking for the optimal dose of TPCA-1. While Dr. Cho is optimistic about the results so far, he says (providing they are still getting successful results) it may be at least 5 years until human trials are possible. “There are still a lot of questions to answer,” he said. “We are still looking at things like what will be the most effective route of delivery of the drug. Do we give it intravenous, inject it directly into the joint, or inject it intramuscularly? This may work differently for humans.”
In the meantime, Dr. Cho and his team will use what they have learned about nanosomes as a platform for new applications of their drug delivery method. They will continue to study other molecules that may be involved in different disease pathways in search of a cure.
Dr. Cho is an assistant professor of orthopedic surgery at The University of Tennessee Health Science Center in Memphis, TN.
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