New Cell Therapies Give Hope to Diabetes Patients
For nearly four decades, George Huntley has thought constantly about his diabetes. Diagnosed in 1983 with Type 1 (insulin-dependent) diabetes, Huntley began managing his condition with daily finger sticks to check his blood glucose levels and doses of insulin that he injected into his abdomen. Even now, with an insulin pump and a device that continuously monitors his glucose, he must consider how every meal will affect his blood sugar, checking his monitor multiple times each hour.
Like many of those who depend on insulin injections, Huntley is simultaneously grateful for the technology that makes his condition easier to manage and tired of thinking about diabetes. If he could wave a magic wand, he says, he would make his diabetes disappear. So when he read about biotechs like ViaCyte and Vertex Pharmaceuticals developing new cell therapies that have the potential to cure Type 1 diabetes, Huntley was excited.
You also won’t see him signing up any time soon. The therapies under development by both companies would require a lifelong regimen of drugs for suppressing the immune system to prevent the body from rejecting the foreign cells. It’s a problem also seen in the transplant of insulin-producing cells of the pancreas – called islet cells – from deceased donors. To Howard Foyt, chief medical officer at ViaCyte, a San Diego-based biotech specializing in the development of cell therapies for diabetes, the tradeoff is worth it.
“A lot of the symptoms of diabetes are not something that you wear on your arm, so to speak. You’re not necessarily conscious of them until you’re successfully treated, and you feel better,” Foyt says.
For many with diabetes, managing these symptoms is a constant game of Whack-a-Mole. “Any form of treatment that gets someone closer to feeling good is a victory,” he says.
“Am I going to be trading diabetes for cancer? That’s not a chance I
want to take."
But not everyone is convinced. What’s more, it’s likely that the availability of these cell therapies will be limited to those with life-threatening diabetes symptoms, such as hypoglycemia unawareness. To Huntley, these therapies remain a bit of a Faustian bargain.
“Am I going to be trading diabetes for cancer? That’s not a chance I want to take,” he says.
The discovery of insulin in 1921 transformed Type 1 diabetes from a death sentence into a potentially manageable condition. Even as better versions of insulin hit the market—ones that weren’t derived from pigs and wouldn’t provoke an allergic response, longer-acting insulin, insulin pens—they didn’t change the reality that those with Type 1 diabetes remained dependent on insulin. Even the most advanced continuous glucose monitors (which tests blood sugar levels every few minutes, 24/7) and insulin pumps don’t perform as well as a healthy pancreas.
Whether by injection or pump, someone with diabetes needs to administer the insulin their body no longer makes. With advances in organ transplantation, the concept of transplanting insulin-producing pancreatic beta cells seemed obvious. After more than a decade of painstaking work, James Shapiro, who directs the Islet Transplant Program at the University of Albania, honed a process called the Edmonton Protocol for pancreas transplants. For a few patients who couldn’t control their blood sugars any other way, the Edmonton Protocol became a life saver. Some of these patients were even able to stop insulin completely, Shapiro says. But the high cost of organ transplant and a chronic shortage of donor organs, pancreas or otherwise, meant that only a small handful of patients could benefit.
Stem cells, however, can be grown in vats, meaning that supply would never be an issue. “We would be going from a very successful treatment of today to a potential cure tomorrow,” Shapiro says.
In 2014, spurred by his own children’s diagnoses with Type 1 Diabetes, stem cell biologist Doug Melton of Harvard University figured out a way to differentiate embryonic stem cells into functional pancreatic beta cells. It was a long process, explains immunoengineer Alice Tomei at the University of Miami, because “the islet is not one cell, it's like a mini-organ that has its own needs.”
Add on the risk of rejection and autoimmunity, and Tomei says that scientists soon realized that chronic and systemic immunosuppression was the only way forward. Over the next several years, Melton improved his approach to yield more cells with fewer impurities. Melton partnered with Boston-based Vertex Pharmaceuticals to create a cell therapy called VX-880.
The first patient received his dose earlier in 2021. In October, Vertex released 90-day results from the Phase 1/2 trial, which revealed the patient was able to reduce his insulin usage from an average of 34 units per day to just 2.9 units per day. The tradeoff is a lifelong need for immunosuppressive drugs to prevent the body from attacking both foreign cells and pancreatic beta cells. It’s what recipients of ViaCyte’s first-gen PEC-Direct will also need. For Foyt, it’s an easy choice.
“At this point in time, immunosuppression is the necessary evil,” he says. “For parents, would you like to worry about going into your child’s bedroom every morning and not knowing if they’re going to be alive or dead? It’s uncommon, but it does occur.”
Not everyone, however, finds the trade-off easy to swallow. Especially with COVID-19 cases reaching record highs, the prospect of reducing his immune function at a time when he needs it most doesn’t sit well with Huntley. The risks of immunosuppression also mean that diabetes cell therapies are limited to those patients with life-threatening complications.
It’s why ViaCyte has created two new iterations of cellular therapies that would eliminate this need. The ViaCyte-Encap contains the cells in a permeable container that allows oxygen, insulin, and nutrients to flow freely but prevents immune system access. Their latest model, PEC-QT, just began safety trials with Shapiro’s lab at the University of Alberta and uses gene editing to eliminate any cellular markers that would trigger an immune response.
Sanjoy Dutta, vice president of research at JDRF International, a nonprofit that funds the study of diabetes, is thrilled with the progress that’s been made around cell therapies, but he cautions it’s still early days. “We have proven that these cells can be made. What we haven’t seen is are they going to work for six months, two years, five years? It’s a challenge we still need to overcome,” he says.
Iowa social worker Jodi Lynn’s concerns echo Dutta’s. Lynn was diagnosed with diabetes in 1998 at age 14 after a bout of severe influenza, spends each day inventorying supplies, planning her food intake, and maintaining her insulin pump and glucose monitor. These newer technologies dramatically improved her blood sugar control but, like everyone with diabetes, Lynn remains at high risk for complications, such as diabetic ketoacidosis, heart disease, vision loss, and kidney failure. Lynn, already considered immunocompromised due to medications she takes for another autoimmune condition, is less concerned with immune suppression than the untested nature of these therapies.
“I want to know that they will work long-term,” she says.
When a patient is diagnosed with early-stage breast cancer, having surgery to remove the tumor is considered the standard of care. But what happens when a patient can’t have surgery?
Whether it’s due to high blood pressure, advanced age, heart issues, or other reasons, some breast cancer patients don’t qualify for a lumpectomy—one of the most common treatment options for early-stage breast cancer. A lumpectomy surgically removes the tumor while keeping the patient’s breast intact, while a mastectomy removes the entire breast and nearby lymph nodes.
Fortunately, a new technique called cryoablation is now available for breast cancer patients who either aren’t candidates for surgery or don’t feel comfortable undergoing a surgical procedure. With cryoablation, doctors use an ultrasound or CT scan to locate any tumors inside the patient’s breast. They then insert small, needle-like probes into the patient's breast which create an “ice ball” that surrounds the tumor and kills the cancer cells.
Cryoablation has been used for decades to treat cancers of the kidneys and liver—but only in the past few years have doctors been able to use the procedure to treat breast cancer patients. And while clinical trials have shown that cryoablation works for tumors smaller than 1.5 centimeters, a recent clinical trial at Memorial Sloan Kettering Cancer Center in New York has shown that it can work for larger tumors, too.
In this study, doctors performed cryoablation on patients whose tumors were, on average, 2.5 centimeters. The cryoablation procedure lasted for about 30 minutes, and patients were able to go home on the same day following treatment. Doctors then followed up with the patients after 16 months. In the follow-up, doctors found the recurrence rate for tumors after using cryoablation was only 10 percent.
For patients who don’t qualify for surgery, radiation and hormonal therapy is typically used to treat tumors. However, said Yolanda Brice, M.D., an interventional radiologist at Memorial Sloan Kettering Cancer Center, “when treated with only radiation and hormonal therapy, the tumors will eventually return.” Cryotherapy, Brice said, could be a more effective way to treat cancer for patients who can’t have surgery.
“The fact that we only saw a 10 percent recurrence rate in our study is incredibly promising,” she said.
Few things are more painful than a urinary tract infection (UTI). Common in men and women, these infections account for more than 8 million trips to the doctor each year and can cause an array of uncomfortable symptoms, from a burning feeling during urination to fever, vomiting, and chills. For an unlucky few, UTIs can be chronic—meaning that, despite treatment, they just keep coming back.
But new research, presented at the European Association of Urology (EAU) Congress in Paris this week, brings some hope to people who suffer from UTIs.
Clinicians from the Royal Berkshire Hospital presented the results of a long-term, nine-year clinical trial where 89 men and women who suffered from recurrent UTIs were given an oral vaccine called MV140, designed to prevent the infections. Every day for three months, the participants were given two sprays of the vaccine (flavored to taste like pineapple) and then followed over the course of nine years. Clinicians analyzed medical records and asked the study participants about symptoms to check whether any experienced UTIs or had any adverse reactions from taking the vaccine.
The results showed that across nine years, 48 of the participants (about 54%) remained completely infection-free. On average, the study participants remained infection free for 54.7 months—four and a half years.
“While we need to be pragmatic, this vaccine is a potential breakthrough in preventing UTIs and could offer a safe and effective alternative to conventional treatments,” said Gernot Bonita, Professor of Urology at the Alta Bro Medical Centre for Urology in Switzerland, who is also the EAU Chairman of Guidelines on Urological Infections.
The news comes as a relief not only for people who suffer chronic UTIs, but also to doctors who have seen an uptick in antibiotic-resistant UTIs in the past several years. Because UTIs usually require antibiotics, patients run the risk of developing a resistance to the antibiotics, making infections more difficult to treat. A preventative vaccine could mean less infections, less antibiotics, and less drug resistance overall.
“Many of our participants told us that having the vaccine restored their quality of life,” said Dr. Bob Yang, Consultant Urologist at the Royal Berkshire NHS Foundation Trust, who helped lead the research. “While we’re yet to look at the effect of this vaccine in different patient groups, this follow-up data suggests it could be a game-changer for UTI prevention if it’s offered widely, reducing the need for antibiotic treatments.”