Canadian scientists Frederick Banting (right) and Charles Best. Image courtesy of Thomas Fisher Rare Book Library, University of Toronto.
From extracting insulin from the pancreas of cows to extreme diets and herbal remedies for glucose regulation, diabetes treatments over the century have evolved progressively, with each discovery extending the life span of patients a little longer than the last.
Clinical gap
The body’s innate ability to produce insulin and maintain normal sensitivity to it is the core deficiency in diabetes. Current treatment options include pancreas transplants and islet cell transplants, which require recipients to take immunosuppressant medication for life that is associated with a lot of side effects. Unfortunately, the scarcity of available donors significantly restricts the widespread implementation of these treatment options. Rather than simply replacing the defective cells or organ, the ideal therapy would address both the root cause – the cell deficiency of insulin-producing beta cells – and the immune system’s attacks on these cells.
Currently, 3.4 million Canadians reportedly have diabetes. Approximately 300,000 are living with type 1 diabetes (T1D), while type 2 affects 90-95 per cent of the diabetic population. Globally, there are 537 million cases of diabetes and, by 2050, projections suggest this number could reach 1.3 billion. A cure for both types couldn’t come a moment too soon.
Stem cell therapy for type 2 diabetes
In a groundbreaking development, researchers from Shanghai Changzheng Hospital, the Centre for Excellence in Molecular Cell Science, and Renji Hospital, have potentially cured a type 2 diabetic (T2D) patient using stem cell therapy.
The therapy involved the transhepatic portal vein transplantation of the patient’s reprogrammed peripheral blood mononuclear cells, capable of regenerating pancreatic islet cells and producing insulin without triggering an autoimmune reaction. This autologous approach avoids the need for lifelong immunosuppression required with allogeneic (donor) cell transplants. The study on this treatment was published in Cell Discovery.
The patient, a 59-year-old man with a 25-year history of T2D and subsequent end-stage diabetic neuropathy, has not needed insulin shots in more than 33 months since receiving this treatment.
Stem cell therapy for type 1 diabetes
Professor Doug Melton, Harvard Stem Cell Institute (HSCI), undertook research to solve the problem of T1D, motivated to find a cure for his children. Professor Melton, in his 30 years of conducting research into diabetes, pioneered protocols together with his team to produce functional pancreatic beta cells from embryonic and induced pluripotent stem cells (iPSCs).
The protocol involves controlling differentiation in vitro using single–cell RNA sequencing. The differentiated cells included other cell populations – alpha and enterochromaffin cells, and only 30 per cent beta cells. The researchers successfully identified CD49a as a cell surface marker specific to β-cells, enabling the sorting of differentiated cells to enhance the purity of β-cell populations. Utilizing anti-CD49a staining in conjunction with magnetic microbeads, the team effectively labelled and isolated β-cells. This approach resulted in clusters comprising up to 80 per cent β-cells, with less than five per cent contamination from enterochromaffin cells.
“The single-cell analysis enabled us to identify gene products that are expressed on the cell surface and could be used to enrich or purify desired cell types,” Melton said to Nature. “In this case, we report on a significant enrichment for β-cells and α-cells: insulin and glucagon-producing cells, respectively.” They used the anti-CD49a staining technique.
In 2015, AstraZeneca partnered with HSCI on a five-year research initiative to clarify the underlying pathology of immune attacks on pancreatic beta cells, investigate the decline in beta cell function and mass, and explore the regeneration of these islet cells from embryonic and iPSCs.
Vertex Pharmaceuticals acquired Semma Therapeutics, a company established by Prof. Melton, in September 2019. This acquisition was intended to integrate his research and expertise into Vertex’s diabetes program, to translate these scientific discoveries into viable therapies for patients with T1D. Shortly after Vertex secured rights from CRISPR Therapeutics to utilize its CRISPR/Cas9 gene-editing technology, VX-880, the product of the research, was approved by the U.S. Food and Drug Administration (FDA) and set for Phase I/II human clinical trials.
The VX-880 works by infusing fully differentiated and insulin-producing islet cells into the liver, which goes on to restore the body’s glucose-responsive insulin production capabilities and boost glucose control. It requires lifelong immunosuppression to prevent the body’s immune system from attacking them.
According to Vertex’s presentation at the recent 83rd American Diabetes Association Scientific Sessions, results showed that amongst the 17 participants, all 12 patients who received the full dose of VX-880 as a single infusion demonstrated islet cell engraftment and glucose-responsive insulin production by Day 90 and 11 recorded reductions or elimination of dependence on exogenous (injected) insulin.
Three patients who were followed past the 12-month mark eliminated severe hypoglycemic events while maintaining an HbA1c level below 7.0 per cent. They were also able to achieve insulin independence.
Overall, VX-880 was well tolerated, with most adverse events classified as mild or moderate. Two patient deaths were reported, but these were not linked to the treatment.
Vertex also acquired FDA approval for the VX-264 program. The VX-264 basically utilizes the VX-880 insulin-producing beta cells, but with an encapsulation device designed to eliminate the need for lifelong immunosuppression and surgically implanted into patients’ bodies. Clinical trials are in progress.
Industry adaptations
The VX-880 trial has been expanded to 37 participants following positive results. In addition to the FDA clearance, Vertex also received approval from Health Canada on the Clinical Trial Application (CTA) for VX-264, and the Phase I/II trial is ongoing in Canada.
Vertex has also announced licensing agreements with TreeFrog Therapeutics and CRISPR to optimize the production of Vertex’s cell therapies for T1D using TreeFrog’s proprietary C-Stem technology, which mimics the natural microenvironment to allow exponential 3D cell growth. The collaboration aims to scale up the process for producing and amplifying fully differentiated islet cells for Vertex’s therapies.
In conclusion, the discovery of insulin in 1921 is said to be the greatest breakthrough in diabetes treatment, until now. With hopes high for this cure, we can move from monitoring glucose levels and treating the complications of this chronic illness to tackling it at the cellular root.
Peace Chukwu
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Great insights on the potential of stem cell therapy for diabetes. It’s exciting to see how research is opening new doors for long-term treatment options. At Advancells, we appreciate content that helps raise awareness about such innovations. Thanks for sharing!
That’s nice to hear. Thanks for taking the time to write.
Interesting; Thanks for sharing such a great article.
Hi Mahsa, thank you for letting us know you liked it.