Tuesday, July 03, 2018 by Frances Bloomfield
As the search for cures to humanity’s most devastating diseases continues, many have turned to nature. Various studies have yielded surprising yet encouraging results from the most unlikely of creatures. In this case, researchers have discovered that the antibodies of sharks, camels, and llamas may hold the key to saving millions of lives.
Compared to human antibodies, the antibodies of these animals are much smaller. Their antibodies are composed of two large pieces known as heavy chains. By contrast, two heavy chains and two light chains or smaller pieces make up human antibodies. While smaller in size, the animal antibodies aren’t any less effective and are, in fact, much more potent thanks to their undersized bulk.
Being tiny in comparison to conventional antibodies means that these miniature ones can access hard-to-reach areas, such as cells and deep tissues. Moreover, they’re easier for scientists to work with and recreate, resulting in even more durable and tinier antibodies typically referred to as “nanobodies.”
It’s this combination of desirable qualities that has caused the smaller antibodies to develop a devoted following. Hidde Ploegh, a biochemist at Boston Children’s Hospital, has called them “exceedingly useful.” Ploegh explained to ScienceMag.com that he and his associates have utilized them for all sorts of projects, ranging from counteracting plant diseases to keeping tabs on an immune protein. Another potential application for these antibodies is in binding and stabilizing proteins to streamline the analysis of the inner workings of minute substances.
The use of these smaller antibodies isn’t limited purely to research, however. In fact, they may be seeing actual usage very soon. The clinical trials of a llama-derived nanobody treatment for acquired thrombotic thrombocytopenic purpura, a rare clotting disease, have concluded. The treatment is slated to receive approval in a select few countries within the year. Moreover, seven smaller antibody-based treatments have entered their clinical trial phase, while at least 30 are currently undergoing further refinement. (Related: Therapy dogs promote healing in the ICU through emotional well-being – proving effectiveness of non-pharmaceutical treatments.)
While ultimately beneficial in the long run, there are a few drawbacks to smaller antibody-derived treatments. There’s a risk of the antibodies leaving the body before they’ve had the opportunity to fully alleviate a patient’s condition. The exact effects and side effects, if any, on human patients are unknown, though a handful of studies have deemed these treatments to be largely safe.
In addition to smaller antibodies, another shark-derived compound worth keeping track of is squalamine. According to MedicalNewsToday.com, this substance can be found in the tissue of dogfish sharks and first rose to prominence in early 2017 due to its effects on Parkinson’s disease.
An experiment with roundworms revealed that oral administration of squalamine could prevent the formation of alpha-synuclein, a protein most often associated with Parkinson’s disease. The manifestation of alpha-synuclein in the brain has been shown to increase the risk of this condition, likely by initiating cell death. Squalamine helped ensure that this build-up never occurred.
“We could literally see that the oral treatment of squalamine did not allow alpha-synuclein to cluster, and prevented muscular paralysis inside the worms,” said researcher Dr. Michael Zasloff.
As for its mechanism of action, study co-author Michele Vendruscolo believes that the gut may hold the answer. “Targeting alpha-synuclein in the gut may perhaps in some cases be sufficient to delay the progress of other aspects of Parkinson’s disease, at least for symptoms concerning the peripheral nervous system,” explained Vendruscolo.
With how positive the study outcome has been, there’s no doubt that nature may indeed be our greatest medicinal asset.