Groundbreaking Study Reveals Potential Cure for Disease Affecting 10 Million Americans

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Scientists believe they might have found a cure for diabetes and other debilitating autoimmune diseases off the back of a groundbreaking new study.

Researchers at NYU Langone Health, the Chinese Academy of Sciences, and Zhejiang University looked at why the body's defense mechanism goes haywire and turns against us, leaving a trail of incurable, life-changing diseases in its wake.

Called autoimmune disorders, these include type 1 diabetes (where the rogue immune response damages insulin-producing cells in the pancreas), multiple sclerosis (MS, where the immune system destroys the protective coating around nerves that control sensation and movement – causing weakness and immobility) and hepatitis (where the immune system mistakenly attacks the liver cells, causing inflammation and damage).

Together, these diseases affect more than four million Americans, but there are many other autoimmune disorders impacting millions more.

Many patients end up on a lifelong cocktail of potent drugs that can reduce the worst of the symptoms but can have unpleasant side-effects – steroids, for example, can cause swelling, weight gain and osteoporosis.

But new research suggests a type of treatment – called LAG-3/TCR Bispecific T cell Silencer or BiTS – could potentially stop all of these incurable disorders in their tracks by 'resetting' the immune system so it ceases its attacks on healthy tissue.

Some experts predict it could be one of the biggest advances in treatment for decades.

T-cells are a type of white blood cell that play a crucial role in the immune system, patrolling the body, including the bloodstream, to identify and destroy harmful cells and organisms.

But sometimes they can struggle to differentiate between healthy cells and those that cause illness or disease, such as cancer or autoimmune conditions, leading the t-cells to mistakenly attack healthy tissue.

One way around this is to tinker with T-cells by exposing them to a drug that alters their DNA, so they produce a protein called chimeric antigen receptor (CAR).

This protein can more easily detect cancer cells that express the target antigen and destroy them.

Once a T-cell becomes a CAR T-cell, it's reproduced in large numbers in the lab and injected a few weeks later back into the patient's body to fight cancer cells.

But treatments focused on T-cells have been elusive because blocking their action broadly weakens the immune system and creates risk for infections and cancer.

CAR T-cell therapy can also have serious effects on the nervous system, leading to a condition known as immune effector cell-associated neurotoxicity syndrome (ICANS).

This can result in symptoms such as headaches, confusion, agitation, seizures  and trouble speaking.

However, the new research in mice published online in the journal Cell, reveals how a newly-designed antibody could help shut down T-cells in a more effective way and prevent these harmful side effects.

The study results are based on the presence of T-cell receptors (TCRs) and checkpoints.

TCRs are turned on by the body's own proteins in autoimmune diseases.

Checkpoints like LAG-3 are also turned on by specific signaling partners, but when this occurs they suppress the T-cell's activity.

This means the T cell's ability to attack other cells, such as cancer cells, is reduced.

By introducing the antibody, it helped to prevent T-cells from damaging the body, focused on regulating their activity and supported the body's natural immune defenses.

This approach is being explored and used in the treatment of various autoimmune diseases.

In autoimmune models of hepatitis, the team's BiTS treatment reduced T cell infiltration and liver damage.

They also treated mice prone to develop multiple sclerosis with short-term, preventive BiTS prior to the onset of disease symptoms, and they reported that BiTS-treated mice had reduced disease by a standard measure.

'Our study... may foster more proximity-based, spatially-guided therapeutic designs like BiTS as immunotherapy for other human diseases,' said co-first author Jia You, a research scientist in Dr. Wang's lab.

'Our findings reveal an intricate mechanism that enables a careful treatment approach to T-cell driven autoimmune diseases, which currently lack effective immunotherapies,' said co-senior study author Dr Jun Wang, assistant professor in the Department of Pathology at NYU Grossman School of Medicine.

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