British and Swedish scientists exploring ways to reverse diabetes have jointly developed a way to use viruses to deliver a gene therapy for reviving damaged pancreatic beta cells.
The researchers are from the Babraham Institute in Cambridge and Uppsala University, Sweden.
In their testing on mice models with type-1 diabetes, the researchers found that the experimental gene therapy reduced the rate of diabetes by 75 per cent. They expect the therapy to work on type-2 diabetes also as the pathway they are targeting is same across both metabolic conditions.
For this, they used the protein shell of a virus and swapped its DNA or RNA with the Manf gene. This gene is known to regulate secretion of insulin by pancreatic beta cells. They observed that the overexpression of the target gene gradually reduced the development of diabetes in the mice.
“What these systems do is make use of the ‘shell’ of a virus to deliver the DNA required to make a therapeutic protein in the targeted cell,” Adrian Liston, Ph D, corresponding author of the study, told Happiest Health.
The researchers targeted the Glis3-Manf axis, a human metabolic pathway which, when disrupted, increases the stress in pancreatic beta cells and ultimately leads to their death. Liston added that this pathway is active in both type-1 and type-2 diabetes, making them hopeful that the experimental therapy will work on both conditions.
They published their findings in the journal Biomolecules.
Understanding diabetes
In type-1 diabetes, there is a loss of insulin-producing beta cells in the pancreatic islets; This results in improper glucose regulation by the body. While the condition is designated as an autoimmune disease, in which the immune cells of the body mistakenly attack the pancreatic islet cells, the condition is caused due to cell stress that leads to the death of beta cells.
One thought is that the autoimmune condition caused beta cell fragility. This means that a partial loss of islet cells forces healthy islet cells to increase their capacity of insulin production. This in turn causes cellular stress and perhaps death in the remaining beta cells.
Viruses as delivery vehicles
Liston’s team employed virus-mediated gene delivery and used the adeno associated virus (AAV) to help protect the brain in the event of traumatic injuries. The researchers engineered AAVs as vehicles to take DNA to the brain – the aim was to reduce inflammation and tissue damage.
This virus vehicle has also been used in cancer therapies and forms the basis of AstraZeneca’s COVID-19 vaccine as well.
“These virus-based drug delivery vehicles don’t cause any side effects or pathological infection in humans,” Kailash Singh, another lead author of the study, told Happiest Health. This is because the protein shell of a virus only helps it get access to cells, while their DNA or RNA genome is the part that is infectious.
The research team plans to further test the efficacy and safety of these models in managing diabetes. It is currently looking out for venture capital investments to run clinical trials including on larger populations.
