Teplizumab, a potential antibody therapy for type 1 diabetes, has a long and complex history. It all started with an antibody called OKT3, which was generated by scientists at Ortho Pharmaceutical in New Jersey in the 1980s. OKT3 was approved in 1986 to help prevent organ rejection after kidney transplants, but it had severe side effects and limited efficacy in treating diabetes.
Researchers outside the company worked to modify OKT3 and eventually created a new antibody, teplizumab, which entered clinical trials in 1999 as a potential treatment for people with newly diagnosed type 1 diabetes. While early studies showed promise, a more extensive follow-up trial failed, and teplizumab was abandoned along with a similar drug called otelixizumab.
Despite these setbacks, Kevan Herold, an immunologist at Yale School of Medicine, remained committed to finding a way to make teplizumab work for people with type 1 diabetes. His persistence paid off, and in 2019, a new study found that teplizumab could delay the onset of type 1 diabetes in people at high risk of the disease. While the therapy is not yet approved for widespread use, it offers hope for people with type 1 diabetes and highlights the importance of persistence in the face of setbacks.
In a recent article published in The Nature, Teplizumab, a drug designed to delay the onset of type 1 diabetes (T1D), is being hailed as a game-changer by patients who have received the treatment, including 16-year-old Claire Wirt, who has been T1D-free for seven years. The one-time treatment, which costs around $194,000, is controversial, with some researchers questioning its cost-effectiveness.
Nevertheless, the drug’s manufacturer, Provention Bio, is running a 300-person trial to test the drug’s efficacy in children and teenagers with T1D. If the trial proves successful, global annual sales of teplizumab could exceed $250 million as a preventive therapy. The drug could also be approved for use in people with stage 3 disease, potentially generating an additional $1.5 billion or more.
Some experts believe the drug could set the standard for developing other prophylactic therapies. However, others point out that trials for autoimmunity are risky, time-consuming, and costly. Novo Nordisk, the Danish pharmaceutical company, is developing a DNA-encoded therapeutic to prevent Type 1 diabetes (T1D) by stopping the immune system from attacking pancreatic cells.
The drug targets T cells that attack the pancreas’s insulin-producing cells, offering safety and efficacy benefits. Once Novo Nordisk has determined a reasonable dose level for people with established T1D, further development could include a prevention trial for people with stage 2 disease.
Meanwhile, researchers are exploring treatments that can be given in infancy to children at risk of T1D, including dietary changes, introducing probiotic bacteria, and giving children powdered insulin. The T1D community’s quest to prevent autoimmunity also informs the development of treatments for other autoimmune diseases, such as rheumatoid arthritis and multiple sclerosis.
In this regard, academic institutes are also looking into the impacts of several additional medications. Some medications enhance and sustain pancreatic function. Many T-cell-targeted medications, in addition to anti-thymocyte globulin, are used to prevent organ rejection.
Yet, Stage 2 intervention may only serve to postpone the inevitable. According to Richard Insel, a former JDRF chief scientific officer, early intervention boosts the probability of reversing the condition. Several human clinical trials focus on persons with type 1 diabetes who have autoantibodies but otherwise have normal blood sugar metabolism.
Some studies are aiming even lower, at stage 1, to uncover medicines that may be used on children at risk of type 1 diabetes. Vaccinations against viruses such as coxsackievirus B, which has been linked to an increase in type 1 diabetes symptoms, and the inclusion of probiotic bacteria in newborn meals have also been studied. So far, powdered insulin has shown the most promise since it can educate the immune system to cease targeting the body’s insulin-producing cells and instead target foreign intruders.
According to a preliminary study, giving newborns oral insulin with breakfast increases the formation of a protective immune cell known as a regulatory T cell, which can prevent future autoimmune attacks. To validate the findings, a larger-scale experiment is required. Type 1 diabetics are not the only ones who want to avoid autoimmunity.
The T1D prevention technique has served as a paradigm for the development of disease-modifying medications for autoimmune diseases such as rheumatoid arthritis (RA) and multiple sclerosis (MS) (MS).”Type 1 diabetes has been our model,” says Paul Emery, a rheumatologist at the University of Leeds in the United Kingdom. More precise descriptions of the pre-disease state and the many phases and diagnostics that may be involved are required for effective RA and MS preventive research.
In a pilot study abatacept, a T-cell-blocking medication showed promise in lowering joint inflammation and delaying the progression of RA in high-risk people. Moreover, researchers have found a medicine that has shown promise in preliminary clinical trials in slowing neurological symptoms in persons with MS who have already sustained some degree of nerve damage to the brain.
