Hi friends 👋🏼,

This week we’ll focus on stories about our immune system and the chaos that ensues when things go wrong:

• Multiple Sclerosis: Challenges & Opportunities ^{READER REQUEST}

• CAR T Therapy Sends Lupus into Remission ^{READER REQUEST}

• Patients Finish Dosing in CRISPR Trial for Diabetes ^{READER REQUEST}

• Inked Up: The Immune Response to Tattoos

🧡 Multiple Sclerosis: Challenges & Opportunities

Multiple sclerosis is the most common central nervous system immune disorder, affecting about 2.8 million people worldwide.

1/ There is no cure for MS, we don’t know the cause for sure, and current treatments only slow the disease’s progression.

2/ The cause of MS is likely multifactorial, involving a person’s genetic predisposition and environmental factors like infectious agents (more on this in a sec), vitamin deficiencies, and smoking. These agents trigger a cascade of complex events, leading the immune cells to become overactive and eat away at our neuron’s protective coating (the myelin), ultimately killing neurons.

3/ Can viruses cause MS? Probably. For example, Epstein-Barr virus (EBV) infects 95% of adults but usually causes no symptoms. However, a study in 2022 looked at 801 people with MS and 1,566 people without MS and found a 32-fold increased risk of developing MS after infection with EBV. This strongly suggests that EBV, in combination with a genetic predisposition, can cause MS.

4/ Atara Biotherapeutics thinks that to cure MS, we may have to stop EBV. They are running a Phase I/II clinical trial to test their leading MS cell therapy drug candidate, ATA188, in people with MS (NCT03282826). Data from this trial are expected in October 2023. So we’ll keep you in the loop.

How does ATA188 work? 👇🏼

ATA188 is made of T cells obtained from a healthy donor previously infected with EBV. It specifically includes a population of T cells primed to recognize EBV to launch an immune attack against infected cells. These T cells are then given to the MS patient and are designed to destroy EBV-infected cells and potentially slow or halt MS progression.

4/ If you want to learn more about other treatments for MS besides cell therapy, this article has a great breakdown of antibody-mediated medicines, plasma exchange therapies, and pharmacotherapies without too much jargon.

🏆 CAR T Therapy Sends Lupus into Remission

Lupus is a chronic autoimmune disease where our immune cells mistake other cells in our body as foreign substances, accidentally turning on us to cause skin rashes, fevers, fatigue, inflammation, and in severe cases, death. The causes are poorly understood, but researchers believe it may be triggered by viral infections (like MS!).

1/ Five people with severe lupus received transfusions of modified immune cells in a groundbreaking study that used genetically altered cells to drive the illness into remission.

2/ All five patients have been completely off their lupus medication for 3 - 17 months! 🥳

How does the treatment work? 👇🏼

The scientists took T-cells from the lupus patients. Then, they modified them using CAR technology (the same technology used to fight cancer successfully) to attack the patients’ B cells on re-infusion. In lupus, B cells produce autoantibodies that attack healthy tissues, but the modified CAR T-cells were “trained” to attack and kill these malfunctioning B cells instead. This led to the wiping out of the patients’ aberrant B cells and dramatic improvement of their condition, ultimately driving the disease into remission.

Blood tests showed that the patient’s B cells recovered about four months after the treatment but no longer produced aberrant antibodies!

What’s next? A larger study with more than five people will be conducted. The exact timeframes were not shared, but we’ll keep you updated.

🩸Patients Finish Dosing in CRISPR Trial for Type 1 Diabetes

1/ In February 2022, CRISPR Therapeutics and ViaCyte made history with their investigational new drug, VCTX210, carrying out the first-in-human transplant of CRISPR-edited, stem cell-derived pancreatic cells to treat T1D. Since then, they have dosed 10 participants in the clinical trial (NCT05210530)

2/ As of February 2023, the companies completed transplanting VCTX210 into all Phase I participants. The data will be released in the coming months, and we’ll keep you updated.

How does VCTX210 work? 👇🏼

The therapy involves engineering stem cells with CRISPR to prevent the stem cells from being destroyed by the patient’s overactive immune system. The stem cells then turn into pancreatic cells, producing insulin and providing a continual supply. Additionally, the cells are housed in a unique device (see image above) that allows for the direct interaction between the patient’s blood vessels and the implanted cells keeping the cells healthy and well-fed over time.

@crisprclassroom

Replying to @esmeraldacolumna @crisprclassroom #crisprclassroom

How is this T1D strategy different from what we wrote in this previous article? The method discussed above directly modifies the stem cells with CRISPR to “hide” from the immune system. In the previous article, it’s the device that the stem cells are put into that protects them from the overactive immune system. Either way, all the progress is excellent news for T1D!

☮️ Inked Up: The Immune Response to Tattoos

Why do tattoos blur over time? The answer lies within our immune system.

1/ Tattoo ink gets eaten by immune cells called macrophages, which cannot digest it. So when ink is visible at the body's surface, it’s not just interlaced among the skin cells; it’s shining out from the bellies of macrophages. 

2/ That macrophage with a belly full of ink can live a couple of weeks or months, but when it dies, it gets gobbled up by another macrophage trying to clean away the debris. Then the ink passes to this second macrophage.

3/ This happens repeatedly, each time moving the ink only a nanometer or so, but over time it leads to the ink creeping and blurring.

Science out here solving problems big and small 😉

Submit a request to our team to research a specific disease or treatment.

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