The wrong antibodies in Joseph Rubash's blood meant that the 11-year-old was at risk for juvenile diabetes — maybe in months, or years, but his parents didn't want to leave it to fate.

The Walker, Minn., child was the first in the state and second in the country to receive Tzield after the drug was approved in November to delay juvenile, or Type 1, diabetes. Rubash returned to Sanford Bemidji Medical Center on Wednesday for the last of 14 infusions of a drug that has been in the making for decades.

"It's not a cure for diabetes ... but if we can get a few more years down the road, who knows where science is going to go in that time," said Joseph's mother, Brenda.

Tzield has kick-started an era of preventive medicine for Type 1 diabetes, which has been diagnosed in 20,000 to 40,000 Minnesotans but is a risk in a larger pool of undiagnosed people. The chronic disease typically emerges in childhood and results from the immune system's unwitting elimination of cells that produce insulin, the essential hormone that converts blood sugar into energy.

Diagnosis often means a lifetime of insulin injections and dietary and exercise restrictions that, if followed, can result in long lifespans. Pancreatic transplants pioneered at the University of Minnesota also can reduce the need for injections and prevent dangerous swings in blood sugar levels. But nothing has halted the autoimmune dysfunction that causes the disease.

"That has been one of the holy grails" for researchers, said Dr. Luis Casas, a Sanford pediatric endocrinologist in Fargo. "How can we get rid of those antibodies?"

The new drug could present a dilemma for families, depending on their share of its $190,000 cost and their willingness to medicate children for diseases they don't yet have. The drug is recommended for children 8 and older with fluctuating blood sugar levels if blood tests show they have at least two of five harmful antibodies.

Two antibodies mean a 90% or more chance of progressing to Type 1 diabetes. Joseph tested positive for all five in 2019, and has other autoimmune diseases along with a family history of diabetes. His parents and caregivers have worried ever since that result.

"The minute this drug came out, the very first child I thought about was Joseph," said Casas, who first treated him for a thyroid irregularity.

Joseph also has Down syndrome. His support team includes his mother, who is a dietitian, and his father, Joe, who is a nurse practitioner and has Type 1 diabetes. The boy loves swimming, biking, football and golf in the northern Minnesota summers. The fifth-grader splits his learning time between school and home.

The 11-year-old also a fascination with science and the body. He lines up stuffed animals at home, pretends they have symptoms and diagnoses them.

The game has helped him comprehend his future with diabetes, but a long delay would be better, his mother said: "We've had four to five years to prepare him for the fact that he will probably need insulin someday. We've been really teaching him how to read labels and how to look at his plate and how many carbohydrates are on his plate and just really prep him to be more independent when the time comes."

The Food and Drug Administration approved Tzield after a clinical trial that compared the drug against a non-medicating placebo in 76 participants with Type 1 risks. Only 43% of patients who took Tzield had diabetes by the study's end — with a median onset of 48 months. In the placebo group, 72% ended up with diabetes — with a median onset of 24 months.

It's unclear whether a two-year delay in diabetes onset will persuade people to take the drug, said Dr. Richard Bergenstal, executive director of HealthPartners' International Diabetes Center in St. Louis Park. Patients and doctors can weigh the benefits and risks — including the side effect of a suppressed immune system during infusions that can worsen any infections.

"This came at a time when we actually have some good therapies for Type 1," he said. "And yet, as good as they are, if you don't have the disease, that would be even better."

Researchers for decades have targeted the autoimmune process that results in Type 1 diabetes. Drugmaker Lilly tried to make teplizumab (Tzield's generic name) work, but abandoned the drug in 2010. Provention Bio acquired the drug's rights in 2018, and experienced setbacks before its favorable trial.

Even that trial had limitations because it involved a small number of mostly white patients with family histories of Type 1 diabetes. Whether the drug works as well in diverse populations is unclear.

Tzield is specific to Type 1 diabetes and not Type 2 — a more common condition that usually occurs with age when insulin-producing cells diminish.

Casas said insurance coverage will influence whether people try the drug, but its cost needs to be weighed against the everyday expenses of insulin injections, test strips and other diabetes supplies. Insulin costs have surged — prompting Minnesota in 2020 to guarantee emergency supplies of the drug when people can't afford it.

"The drug is expensive but diabetes also is expensive," Casas said.

Provention has pledged rebates to help with costs not covered by insurance, and the Rubash family has applied for the assistance.

The drug's availability will likely increase antibody testing.

"Now that we have something to offer, we are more likely to have families who would want to know," Casas said.

Joseph's risks were discovered through enrollment in TrialNet, a national research group including Sanford and the U that has tested more than 200,000 people with family histories of Type 1 diabetes. The researchers over the past two decades have discovered the stages preceding the disease and the likelihood that they result in diabetes.

Sanford expanded on that effort by offering antibody screening to all pediatric patients, regardless of family history. Casas said Sanford is reviewing those patients to see if any meet criteria for the drug. Some had been waiting for it but lost that option when they were diagnosed with diabetes.

Joseph was fortunate to still be eligible, Casas said: "It buys us another three to four years to try to find a permanent treatment to prevent him from ever actually getting it."