In the fight against Type 1 diabetes, drugmakers are pursuing a new line of attack: creating cells that help the body beat the condition.
In Type 1 diabetes, the immune system attacks pancreas cells that make insulin, a hormone that helps cells absorb sugar. Some 1.25 million Americans have the condition, which raises the risk of heart disease, nerve damage, kidney failure and other illnesses. Patients typically tackle the disease with diligent glucose testing and insulin therapy, used to control blood sugar or glucose.
In the past few years, scientists have made significant progress in their efforts to free patients from insulin therapy. Researchers have learned more about how to generate insulin-producing cells in a laboratory and place them into patients, while protecting the cells from the immune system, which would ordinarily reject them. Some are reprogramming the patient’s own cells to retrain them to fight the disease.
“It is [in] no way an easy life trying to manage blood glucose,” says Julia Greenstein, vice president, discovery research, for JDRF, a nonprofit that funds research into Type 1 diabetes.
Currently, a pancreas transplant is the gold standard for freeing patients from insulin therapy because it enables the highest percentage of patients to remain independent of the treatment over the long term, says Peter Stock, a professor of surgery at the University of California, San Francisco, and co-director of the Pancreatic Islet Cell Transplant program at UCSF Medical Center.
But a pancreas transplant is a major surgery, and not every patient has a heart healthy enough to tolerate the procedure. Transplants also require immune-suppressing drugs, which increase the risk of infection and certain cancers. And the procedure requires donor pancreases, which are scarce.
A less invasive option, which has been around since the 1980s, is transplanting islets, or clusters of pancreas cells that include insulin-making beta cells. Patients receive them through a direct injection into the vein that leads to the liver. Some islet-transplant recipients can forgo insulin therapy for several years.
Yet islet transplants carry some of the same downsides as full organ transplants. A pancreas must be removed from a deceased donor to obtain the islets, even though the organ isn’t actually being transplanted. And the treatment requires immune-suppressing medication to prevent the patient’s body from rejecting donated cells. So, like organ transplants, islet procedures are reserved for a small minority of patients.
The cures under study now would remove the need for a donor pancreas. In the first method, cells that could free patients from insulin therapy are generated in a laboratory and then transplanted into a patient.
“Everyone’s waiting for the next generation of beta-cell replacement that hopefully will change the whole way in which we treat diabetes,” says Gordon Weir, a Harvard Medical School professor and diabetes researcher at the Joslin Diabetes Center in Boston. “In spite of the excitement and extraordinary things that have happened in the last 10 years, there are still a lot of challenges.”
Biotechnology companies ViaCyte Inc. and Semma Therapeutics Inc. hope to solve the donor-shortage problem by coaxing stem cells to mature eventually into other cells that make insulin and other hormones.
In 2014 ViaCyte, of San Diego, began clinical trials of progenitor cells—which turn into pancreas cells—housed in a device that protected them from the immune system. Company scientists hoped a network of blood vessels would grow on the device implanted under the skin. Then oxygen, glucose and other nutrients could diffuse through its tiny pores, allowing cells inside to thrive and function. Meanwhile, insulin and other hormones would diffuse out.
But in the study, certain immune cells interfered with the creation of this blood-vessel network. ViaCyte is hoping to improve the device to prevent this response, and resume clinical studies within 24 months.
Meanwhile, it is starting new studies of a device with larger pores that let blood vessels enter and nourish the progenitors directly. Since this approach wouldn’t protect the cells inside the device from the immune system, patients would need immune-suppressing drugs. But the treatment could make cures more accessible to patients at high risk for life-threatening diabetes complications who would also be islet-transplant candidates, according to Chief Executive
Semma, meanwhile, formed in 2014 around research from the Harvard Stem Cell Institute that led to a means of generating billions of insulin-making beta cells in the lab. Similar to ViaCyte, the cells would be placed in a device that is implanted in the body and protects the cells from the immune system.
Semma, of Cambridge, Mass., hasn’t said when human studies will begin. “We want to create hope but not hype,” says CEO
Other companies are taking a different approach to working with cells. Instead of replacing those that make insulin,
and Parvus Therapeutics Inc. seek to salvage and restore function to cells that are damaged.
Parvus drugs reprogram immune cells that harm the body’s own pancreas cells into “regulatory T cells” that suppress diabetes. This is “reprogramming a killer to [be] a peacemaker,” says Parvus Chief Scientific Officer Pere Santamaria. Parvus, based in Calgary, Alberta, has licensed rights to this Navacim technology in Type 1 diabetes to
Caladrius is harvesting the patient’s own regulatory T cells, which aren’t functioning normally, says Douglas Losordo, senior vice president, clinical, medical and regulatory affairs, and chief medical officer of Caladrius. Caladrius then increases the number of these cells, repairs them and returns them to the patient in a bid to restore balance to the immune system. Caladrius, of Basking Ridge, N.J., is testing the treatment in clinical trials.
Patients are following curative research efforts closely. Dara Melnick, of Woodbury, N.Y., was diagnosed with Type 1 diabetes when she was 8 years old and is now 36. She said she tests her blood sugar 20 times a day but remains concerned about future diabetes-related health risks.
“A cure would be the sweetest thing I could ever taste,” Ms. Melnick says.
Mr. Gormley is a special writer for The Wall Street Journal in Boston. Email him at [email protected].