What If the Immune System Could Start Over?

Good Morning.

Rheumatoid arthritis begins with a mistake.

The immune system, designed to defend the body, begins attacking the body's own joints. The result can be years of inflammation, swelling and pain.

Medicine has become increasingly good at controlling that attack.

But researchers in Germany are testing a very different possibility.

What if, instead of repeatedly suppressing the immune response, they could remove some of the cells responsible for sustaining it?

The approach comes from an unexpected place: cancer treatment.

CAR T-cell therapy takes a patient's own T cells and genetically modifies them in the laboratory so they can recognize a particular target. In some blood cancers, that target is found on malignant B cells.

Researchers at Charité in Berlin wondered whether the same strategy could be turned against the B cells involved in severe rheumatoid arthritis.

They treated six people whose disease had resisted numerous previous therapies.

After a single CAR T-cell infusion, disease activity fell substantially in all six. Three remained in remission without rheumatoid arthritis medication during follow-up of up to a year.

But what happened inside their immune systems may be even more interesting.

The engineered cells appeared to reach disease-associated B cells hidden in joint tissue, lymph nodes and bone marrow. Those cells were depleted. Later, as the B-cell population recovered, researchers predominantly saw naïve B cells that had not yet been shaped by the disease. The disease-associated B cells present before treatment were no longer detectable in almost all of the patients.

It's an early glimpse of what researchers call resetting pathological immune memory.

There are important reasons for caution. Six patients cannot establish that the treatment is broadly effective or safe, CAR T therapy itself is intensive, and one participant's disease returned after an initial medication-free remission. A second phase will compare the treatment with an existing rheumatoid arthritis drug in ten additional patients.

Still, the experiment points toward an intriguing possibility.

Some autoimmune diseases may eventually be treated differently from the way they are today.

Instead of asking how long the immune system can be kept under control, medicine may increasingly ask whether some of its mistakes can be undone.

Source: Charité Berlin. Research published in Nature Medicine.

A Quick Note From Yesterday

Yesterday, we asked a question we were genuinely curious to hear your answers to:

If you could pause aging at any age, what age would you choose, and why?

We had a small glitch with our reply email yesterday, so your responses weren't reaching us.

That's fixed, and we'd still love to hear your answer. You can reach us at [email protected]

If you missed yesterday's issue, you can read it here. Just be sure to send your answer to [email protected], since the reply address in that issue is the one that wasn't working.

We may share some of your responses in a future issue.

Longevity

The Long Game
One small thing for a longer life

Did You Know

Cardiorespiratory fitness is one of the strongest predictors of how long you may live.

When the Cleveland Clinic tracked more than 120,000 people who took a treadmill test, those with the lowest cardio fitness had about five times the risk of dying over the following years compared with the fittest, an association on par with, or greater than, major risk factors such as smoking and diabetes. And researchers found no point at which higher fitness stopped being associated with lower mortality risk.

Movement is one of the six factors that shape how well we age. The Worthyest Longevity Index measures all six in 4 minutes. Yours, personalized. Get my score →

Source: Mandsager et al., JAMA Network Open, 2018. Cleveland Clinic study of 122,000+ adults.

The Curiosity Edit

Today’s Insight: Metabolic Health

Your Waist Size May Reveal Health Risks BMI Misses

The number on the scale doesn't always tell the whole story. New research suggests one of the simplest measurements may reveal health risks that BMI can overlook. Read the full story here.

Modern Living:

Brain Health

How Exercise May Change the Brain’s Emotional Networks

We know exercise can change how we feel. Researchers are beginning to see what those changes may look like inside the brain itself. Read the full story here.

Health & Wellness

Small Habits, Important Signals

Some health questions are surprisingly ordinary: how we clean our hands, how much we sleep, and which changes in the body deserve attention. This collection looks at everyday prevention alongside two areas where recognizing the right signals can make a difference.

What's More Effective: Washing Your Hands or Using Hand Sanitizer? Medical Experts Weigh In
Soap and water and hand sanitizer both help protect against germs, but they aren't interchangeable in every situation. Medical experts explain when each works best and why the difference can matter.

Signs and Symptoms of Cancer
Many possible signs of cancer can also be caused by conditions that are far less serious. Knowing which persistent or unexplained changes deserve a conversation with your doctor can help separate ordinary symptoms from ones worth investigating.

Too Much or Too Little Sleep May Make Your Body Age Faster
Sleep duration has been linked to health in countless ways, but researchers are now examining it through the biology of aging itself. A new analysis using 23 measures of biological age found an intriguing pattern at both ends of the sleep spectrum.

The Conscious Plate:

Food, Nutrition & Elevated Living

What Food Can Change

What we eat can influence the body in ways that extend well beyond hunger. This collection looks at new findings on diet and metabolic health, what omega-3s may do for mood, and how to choose what to eat before a workout.

Keto Diet Cut Liver Fat by 67% in a Clinical Trial
Three popular approaches to eating produced similar weight loss in a recent clinical trial, but their effects inside the body weren't identical. One diet produced particularly striking results for liver fat and other measures of metabolic health.

What Happens to Your Mood When You Take Omega-3s Regularly?
Omega-3s are usually discussed in connection with heart and brain health, but researchers have also studied their relationship with mood. Here's what the evidence suggests about whether regularly getting enough could make a difference in how you feel.

Protein vs. Carbs: Which Is the Better Pre-Workout Snack?
What you eat before exercising can affect how prepared your body is for the work ahead. Dietitians explain what protein and carbohydrates each bring to a pre-workout snack and when one might deserve more room on the plate.

Final Note

This is what we leave you with. A thought to end the day, carry in your pocket, or come back to later. Nothing big. Just something to reflect on.

When Life Changes Before You Notice

The biggest changes in life usually arrive one ordinary day at a time.

We expect change to have a before and an after. Often, there isn't one.

A new routine becomes normal. Someone becomes important to us. A child needs us a little less. Work begins taking us somewhere we hadn't planned.

Then one day we look around and realize life is different.

The change was happening all along. We just couldn't see it while we were living through it.

Pass It On

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