Introduction

An innovative antibody developed as a potential treatment for amyotrophic lateral sclerosis (ALS) has successfully prevented the rejection of kidneys transplanted into non-human organs.

Improving Organ Transplant Procedures

If human clinical trials successfully prove its safety and effectiveness, this treatment could significantly improve organ transplant procedures in the future.

“This less toxic approach has been around for more than 20 years, and I think we’ve finally reached a turning point,” says immunologist and transplant surgeon Alan Kirk of Duke University. “This could be a big advance for people who need a transplant.” organs.”

The Challenge of Organ Rejection

Organ transplantation is a life-saving procedure, but the body’s immune system often interferes with the success of the operation by recognizing the transplanted organ as foreign and attacking it.

The immune response, known as organ rejection, can lead to failure of the transplanted organ and, in extreme cases, death.

The Role of AT-1501

The study found that the monoclonal antibody “AT-1501” helped reduce the incidence of rejection without increasing the need for immunosuppressive drugs or causing an increase in blood clots, which were a side effect of the previous treatment option.

Eledon Pharmaceuticals, which is developing AT-1501 under the brand name Tegoprubart, partially funded the study.

“Current drugs to prevent organ rejection are generally good, but they have many side effects,” says surgeon scientist Imran Anwar of Duke University. “These treatments suppress the immune system, exposing patients to the risk of infection and organ damage, and many of them cause non-immune complications such as diabetes” and high blood pressure.”

How AT-1501 Works

Monoclonal antibodies, such as AT-1501, are designed to work like human antibodies by cloning one type of immune cell. AT-1501 targets a specific protein called CD40 ligand found on the surface of some T cells, a type of white blood cell involved in the immune response.

AT-1501 acts against T cell activation by binding to CD40 ligand. Inhibiting T cell activation in this way helps prevent multiple immune and inflammatory responses that contribute to organ transplant rejection.

Testing and Results

To confirm its safety and effectiveness in kidney transplantation, AT-1501 was tested in rhesus monkeys and pancreatic islet transplantation in cynomolgus monkeys.

It turns out that animals treated with AT-1501 after transplantation had relatively fewer complications, such as weight loss or reactivation of latent cytomegalovirus, which are often observed after traditional methods of suppressing the immune system.

“These data confirm that AT-1501 is a safe and effective agent for improving islet and kidney graft survival and function and allow us to immediately advance it into clinical trials,” Kirk says.

“The trend in recent decades has been to develop new, less toxic drugs,” explains Anwar. “We hope that this antibody will bring us closer to this goal.”

Conclusion

The study was published in the journal Science Translational Medicine.

Source: ScienceAlert