A set of small molecules called microRNA (miRNA), found in a recent study, show potential both as biomarkers and as therapeutic targets of Gaucher disease.
Determining differences in the levels of these miRNA among Gaucher patients could lead to insights into disease mechanisms and to new therapeutic targets, as well as to biomarkers that could be used to track both disease progression and treatment effects, researchers said.
The study, “MiRNA Expression in Patients with Gaucher Disease Treated with Enzyme Replacement Therapy,” was published in the journal Life.
RNA is best known as a set of protein-making instructions. Some scientists suspect that a class of small non-protein-coding RNA, called miRNA, could help to explain the diversity between the three types of Gaucher disease that exist, each with its own varying symptoms and outcomes.
Type 1 can appear at any age and typically involves blood-related and bone complications, as well as an enlarged liver and spleen. In turn, types 2 and 3 involve the central nervous system, comprised of the brain and spinal cord, with type 2 progressing more aggressively.
The miRNA molecules interfere with protein production by muting a protein’s associated gene. However, relatively few studies have investigated the role of miRNA in Gaucher disease.
Now, scientists from the Jagiellonian University, in Kraków, Poland, sought to address this knowledge gap. They screened 20 adults with Gaucher type 1 — all treated with enzyme replacement therapy (ERT) — and 10 healthy people (controls).
The study found 30 miRNA whose expression differed significantly between the Gaucher patients and the healthy controls. All of the miRNA in this set were found at higher levels in patients relative to controls.
Gaucher disease arises when mutations in the GBA gene result in a deficiency of beta-glucocerebrosidase, known as GCase. This enzyme breaks down glucocerebroside, allowing toxic levels of that molecule to accumulate inside cells. Notably, glucocerebroside is made of a fatty acid chain, among other components.
Two miRNAs — miR-195-5p and miR-16-5p — are associated with fatty acid synthesis and metabolism. These two molecules were linked in prior research to increased GCase activity. As such, this may mean that a GCase deficiency leads to an increased amount of regulators such as the two miRNAs, the scientists said.
Another miRNA that drew the researchers’ attention was miR-26b-5p, which associates with bone and cartilage growth. Bone abnormalities are highly likely to occur in Gaucher, usually in the spinal cord and long bones, which are known as the Erlenmeyer flask bone deformity.
Other miRNA in the set are known to participate in Gaucher-associated biological pathways, including cell signaling and the interaction between cells and their surroundings. They also participate in cancer pathways.
The small amount of existing data concerning how exactly Gaucher affects these pathways and the role that miRNAs could play in them drives the need for more and better biomarkers to help track the disorder’s progression and to evaluate treatment effectiveness, according to the researchers.
All patients in the study had been on ERT for at least two years. Although the effect of ERT on miRNA expression is not well-known, the investigators see their results as providing a useful set of biomarkers to investigate more fully in the future.
“We highlighted some miRNA compounds that showed remarkable alteration in those patients and might be potential biomarkers,” the researchers concluded. “However, due to scarce data on [Gaucher disease], these findings need further studies.”
