A century ago, type 1 diabetes was a death sentence. But San Diego biotech ViaCyte says two studies published this week show the company is getting closer to what it calls a "functional cure" for the disease.
The pair of studies, published last week, are based on an early-stage clinical trial in which the company implanted small devices beneath the skin of type 1 diabetics. These devices were loaded with pancreatic cells, which researchers showed could grow into cell types that naturally keep your blood sugar from dipping too low or suddenly spiking.
The hope is that this approach, known as cell replacement therapy, could allow type 1 diabetics to ditch the needles, syringes and pumps they use to constantly monitor their blood sugar. But first, the reported findings, based on the first batch of patients to join an ongoing study, must hold up as the trial expands and in follow-up trials. And ViaCyte is still tinkering with its device to trigger insulin production more consistently and robustly.
Still, the latest findings are sparking genuine optimism from a company that's run into numerous twists and turns in its quest to treat what remains a difficult and devastating disease.
"The cells that we are implanting actually work — they secrete insulin," said Dr. Howard Foyt, ViaCyte's chief medical officer. "We've done it already. So it's just a question of being able to reproduce those results in a greater number of patients."
The recent studies come about a month after Vertex, a Massachusetts biotech company, also announced that it has made progress toward a cell-based therapy for type 1 diabetes.
It's all part of an effort to help those struggling with a disease that affects 1.6 million Americans, according to the Juvenile Diabetes Research Foundation. Type 1 diabetics often suffer from constant exhaustion, weight loss and increased thirst and urination, among other symptoms.
Things can get worse without treatment, leading to heart, kidney and nerve damage. A second-century Greek physician once described diabetes as "the melting down of flesh and limbs into urine."
At the source of these patients' woes is friendly fire from their own immune systems, which wipe out the cells in the pancreas that make insulin, a hormone that regulates blood sugar levels. And while type 1 diabetics can inject themselves with insulin and use glucose monitors to track their blood sugar, these fixes are expensive and not always effective.
ViaCyte is betting that replenishing these lost cells would be a more lasting solution. Researchers have known for about 20 years that transplanting pancreatic cells from organ donors can trigger insulin production, but there's not enough donor tissue to keep pace with demand. So the biotech is using stem cells, which can be grown in bulk and coaxed to form virtually any of the body's cells.
One of the company's implants, known as PEC-Direct, is about half the size of a credit card and loaded with millions of pancreatic cells derived from stem cells. These cells can further develop into beta cells, which produce insulin and lower blood sugar, and alpha cells, which make glucagon, a hormone that raises blood sugar.
Foyt thinks the combination of both cell types could avoid a silent but deadly problem for some type 1 diabetics — dangerously low blood sugar that starves the brain of glucose, leading to comas, seizures or even death.
The biotech's small, flexible device slips beneath the skin — usually under a person's forearm or the sides of their lower back — and is covered with teeny pores that let blood vessels snake inside and supply cells with oxygen and fresh nutrients. But those pores also allow the patient's immune cells to attack the transplanted cells, so recipients need immune-suppressing drugs to keep the new cells alive.
The company is also exploring whether it can genetically modify the cells so that immunosuppressants won't be necessary, but that effort is still at an early stage.
The recent studies, published in the journals Cell Stem Cell and Cell Reports Medicine, looked at 15 and 17 patients, respectively, taking part in an early-stage clinical trial of ViaCyte's implant launched in 2017. The latter study found that six of the 17 participants who got the implant started making detectable levels of a molecule called C-peptide, which is created when insulin is produced.
Why didn't the researchers measure insulin directly? Because patients were still receiving direct insulin injections. But the only way they'd have C-peptide would be if they were also making insulin themselves.
"We obviously hoped for more," said Foyt of the fact that about a third of participants made their own insulin. "(But) nobody has ever been able to do that before. And so that's why we reported it."
The amount of insulin made by trial participants wasn't high enough that they no longer needed injections of the hormone, but its production followed a familiar and reassuring pattern, going up after patients ate and eventually back down.
That's exactly what happens in non-diabetics, suggesting that the transplanted cells were sensing and responding to blood sugar normally. And when researchers removed the implants from participants for a closer look, they found the devices filled with both alpha and beta pancreatic cells, just as they'd hoped.
The company has since tweaked the design of its device, adjusting the number of tiny holes, their locations and how many implants each participant receives to help participants make enough glucose-regulating hormones to keep their blood sugar in a healthy range. Foyt says the biotech expects to have results from another eight patients by August.
ViaCyte's work parallels that of Vertex, which in mid-October reported that a type 1 diabetic from its own ongoing clinical trial had started producing insulin after receiving stem cell-derived pancreatic cells. Notably, the participant needed about 90 percent less injected insulin to control their blood sugar three months after treatment than they did before the study.
But these findings are based on a single patient and were announced in a press release rather than a scientific journal. And Vertex's treatment is a direct injection of cells into the liver. By comparison, Foyt says that ViaCyte's use of a device that holds onto the cells makes it easy to remove the implant if anything goes wrong, which could prove a handy advantage.
ViaCyte, founded in 1999, has about 125 employees in Torrey Pines. In that time, it's come up with a number of ways to deliver pancreatic cells to diabetes, none of which have yet to receive regulatory approval. But Foyt's convinced the company is on the right track.
"Over the last seven to eight years, we've been going step by step, overcoming one obstacle only to encounter another," he said. "There's no doubt in our mind that the cells work. The challenge has been the engineering to figure out how to get the cells into the body in a way that will allow the cells to do their thing."
