Turning a promising discovery into a patient therapy takes years of research and strong partnerships.
That is exactly what two leading biotechnology companies have done.
ViaCyte and CRISPR Therapeutics have combined stem cell science and gene-editing technology to develop a potential new treatment for type 1 diabetes (T1D). The therapy recently received Health Canada clearance to enter clinical testing.
A New Approach to Type 1 Diabetes
CIRM has supported ViaCyte’s work for many years, investing more than $72 million through nine awards.
ViaCyte developed an implantable device that contains cells derived from human embryonic stem cells. These cells mature into pancreatic progenitor cells, which can develop into insulin-producing islet cells.
Type 1 diabetes occurs when the immune system destroys the body’s insulin-producing islet cells.
Without insulin, the body cannot properly regulate blood sugar levels.
Researchers hope the implanted progenitor cells will mature into functional insulin-producing cells. In theory, those cells would monitor blood glucose and release insulin when needed.
If successful, the therapy could provide a more natural way to control blood sugar and reduce the burden of disease management.
Engineering Cells to Evade the Immune System
One of the biggest challenges in cell therapy for type 1 diabetes is the immune system itself.
Even if researchers replace the lost cells, the immune system may attack and destroy them.
Many transplant recipients require immunosuppressive drugs to prevent rejection. Those medications can carry significant side effects and risks.
To address that problem, ViaCyte and CRISPR Therapeutics developed a new therapy called VCTX210.
The treatment combines stem cell technology with gene editing. Researchers designed the implanted cells to evade immune detection.
The goal is to protect the therapeutic cells without requiring long-term immune suppression.
This version of the therapy grew out of earlier CIRM-supported research and development efforts.
Moving a Promising Therapy Into the Clinic
Receiving regulatory clearance to begin a clinical trial marks an important milestone.
In a company announcement, ViaCyte President and CEO Michael Yang described the approval as a major step forward.
“Being first into the clinic with a gene-edited, immune-evasive cell therapy to treat patients with type 1 diabetes is breaking new ground,” Yang said.
He noted that eliminating the need for immunosuppression could significantly expand the number of patients eligible for cell-based therapies.
Researchers ultimately hope the approach will move the field closer to a functional cure for type 1 diabetes.
The upcoming clinical trial in Canada will focus on several key questions:
- Is the therapy safe?
- Does implantation cause adverse reactions?
- Can the engineered cells successfully evade the immune system?
- Can the cells survive and function after transplantation?
The answers will help determine whether the therapy can advance to larger studies.
Building on Years of Progress
The trial represents the latest chapter in a long effort to develop regenerative medicine approaches for type 1 diabetes.
Scientists have already shown that stem cell-derived pancreatic cells can survive and mature after transplantation. The next challenge is protecting those cells from immune attack.
By combining stem cell biology with gene editing, ViaCyte and CRISPR Therapeutics hope to overcome that barrier.
If successful, the approach could help deliver a lasting source of insulin-producing cells and move researchers closer to a transformative treatment for people living with type 1 diabetes.
Here’s an excerpt from that podcast.
For PEC-OT, ViaCyst’s propriety Cy749 pluripotent stem cell line specifically engineered to avoid destruction by the patient’s immune system, and hence cells are being designed to be immune evasive. This designing cells is in favor of eliminating the need for immunosuppressants. Indeed, engineered allogenic stem cells are able to differential into pancreatic endoderm cells and allow direct interaction between blood vessels and implanted cells. This commercialize gene-edited allogenic stem cells ,hopefully can be widely used in future for cells derived therapy.
The safety and efficacy of VCTX210 require further observations to make sure long-term benefit to patients with type1 diabetes. 1)Most genetically modified cells have unstable genotype. Although, they may provide short-term benefits to patients with cell-based therapy. The engineered cells take time to turn around into cancerous cells, this may pose long-term serious health issue and life-threatening to patients. 2)In nature, adult vertebrates require processes of development and tissue maintenance for replenishment of skin, intestine and the hematopoitic stem cells. They require stem cells to proliferate further to produce the functionally mature, postmitotic cells for replacing those lost through natural processes. The stem cells themselves are capable of self-renewal to replace those that become committed to differentiation. During the process of cell proliferation and differentiation lead to rapid production of abnormal cells which are removed by autoimmune response. Hence, engineered allogenic stem cells with ability of immune evasive face high risk of developing cancerous cells. 3)Tissues and organs of human’s body are frequently exposed to rapid changes of pH, body temperature, toxic compounds and inflammatory elements. The engineered cells are not protected by devise of pouch may easily lose its stability of cell genotype and phenotype.
Therefore, patients required long-term follow up to determine their health issues . Both safety and efficacy of cell-based therapy are paramount importance to safeguard long-term benefit of patient’s health and life.