Hi friends 👋🏼,

We started this newsletter on March 12 and, so far, have written stories about 36 of your requests! If you enjoy The Cure, please forward us to your friends and colleagues. This week we’ll cover…

• Targeted Cell Therapy for Pancreatic Cancer ^{READER REQUEST}

• Immunotherapy Delivers Promising Results for Thyroid Eye Disease ^{READER REQUEST}

• Fighting Kidney Failure: Alport Syndrome ^{READER REQUEST}

• Uncertainties Surround Adult Onset Nemaline Myopathy ^{READER REQUEST}

⚡️ Targeted Cell Therapy for Pancreatic Cancer

Your pancreas releases enzymes that aid digestion and produces hormones that help manage blood sugar (e.g., insulin). Unfortunately, pancreatic cancer is seldom detected early because it often does not cause symptoms until it has spread to other organs.

1/ Current treatments for pancreatic cancer include chemotherapy and radiation therapy. However, these treatments harm not only cancerous cells but also healthy cells.

Can we develop a new targeted therapy that preferentially kills pancreatic cancer cells and leaves the healthy ones alone? 👇🏼

2/ That’s exactly what doctors at the University of Pennsylvania are testing in a new treatment called huCART-meso cell therapy (NTC03323944).

Here’s how it works:

1. First, the patient’s T cells are collected with a blood draw.

2. Over several weeks, these T cells are genetically engineered in a lab to add a new protein called a CAR (chimeric antigen receptor) (see image above).

   • This particular CAR is developed to target a protein called mesothelin, which is overexpressed on the surface of most pancreatic cancers.

   • Specifically, they take a lentiviral vector (a virus with all the harmful bits removed that can be used as a cellular delivery truck) to deliver the CAR receptor targeting mesothelin to the patient’s T cells.

3. Once engineered, they take the CAR T cells targeting mesothelin, and they will test injection with two formats in separate patient cohorts:

   • First, intravenous injection of the CAR T cells directly into the patient’s blood.

   • Second, local delivery of the CAR T cells injected within the patient’s pancreas.

3/ This clinical trial is currently recruiting 18 patients to participate. If you are interested in joining, you can provide your oncologist with the clinical trial number (NTC03323944) or contact the Abramson Cancer Center directly at [email protected].

👁️ Thyroid Eye Disease: New Immunotherapy Delivers Promising Results

Thyroid Eye Disease (TED) is an autoimmune disease in which your body’s immune system attacks the tissues around the eyes, causing swelling and inflammation, redness, puffy eyelids, and a gritty sensation that feels like sand in the eyes (see photo above, left).

1/ What causes TED? It’s not fully understood, but we observe that people with TED overexpress a specific protein called IGF-IR.

2/ Based on this observation, scientists at Viridian Therapeutics have developed an antibody treatment, VRDN-001, that specifically targets IGF-IR and reduces its activity.

3/ In Phase 2 clinical trials, VRDN-001 reduced eye bulging by an average of 2.3mm and eliminated double vision in 54% of trial participants. (These results were just announced this past week!)

4/ The Phase 3 clinical trial for VRDN-001, NCT05176639, is now recruiting. Learn more about the hospitals performing these trials here, and talk to your doctor about getting involved.

How does VRDN-001 treatment compare to TEPEZZA, the only FDA-approved IGF-IR antibody treatment currently available for TED?

While we can’t know for sure since there has been no direct head-to-head comparison, we can gain a little insight by looking at the CAS scores* for the VRDN-001 and the TEPEZZA clinical trials: While only 22% of trial participants had complete or near complete elimination of TED symptoms for TEPEZZA, 62% of trial participants had complete or near complete elimination of TED symptoms for VRDN-001. Though both TEPEZZA and VRDN-001 use antibodies to block IGF-IR activity, it seems the VRDN-001 antibody has a more complete blockade.

*CAS scores = clinical activity score, a composite scale scoring all signs & symptoms of TED.

🥊 Fighting Kidney Failure: Alport Syndrome

Alport syndrome is a disease that damages the tiny blood vessels in the kidneys leading to kidney disease and, ultimately, kidney failure.

1/ What causes Alport syndrome? X-linked Alport syndrome, the most common form, is caused by mutations in the type IV collagen gene COL4A5. Type IV collagen acts like a barrier between tissue compartments and is essential to the function of the kidneys, inner ear, and eyes.

2/ Currently, no treatments are available or are being tested in clinical trials that target the underlying causative mutation in COL4A5. All treatments being tested in clinical trials attempt to mitigate the major life-threatening symptom of Alport - kidney disease.

3/ River 3 Renal Corp. is developing R3R01 to treat Alport-related kidney disease. R3R01 is a new molecule that is thought to increase the level of a particular transporter (ABCA1) in the kidney that can help reduce fat that builds up and, in so doing, improve kidney function and longevity. The clinical trial testing R3R01 is actively recruiting patients (NCT05267262). To inquire about joining the study, contact [email protected] or [email protected].

4/ But if we look at preclinical studies, we see scientists using CRISPR to target COL4A5 directly and correct it. For example, in one study, scientists used CRISPR gene editing to correct the COL4A5 gene with 58.8% efficiency when editing cells in a dish. The scientists behind the works said, “We are therefore strongly convinced that [Alport syndrome] will become a treatable disorder in the near future by gene-editing.”

We’ll keep you updated as the science progresses with X-linked Alport syndrome!

⍰ Uncertainties Surround Adult Onset Nemaline Myopathy

Nemaline Myopathy is a disorder that primarily affects skeletal muscles and causes muscle weakness throughout the body. It has several forms in order of decreasing severity: congenital, Amish, childhood-onset, and adult-onset. We’ll focus on the adult-onset form here.

Adult-onset nemaline myopathy is hard to diagnose accurately, there can be several potential causes, it’s treated in different ways, and there are no ongoing clinical trials. 😅

So how do we move forward in the face of such uncertainty?

Step 1 - Learn more about adult-onset nemaline myopathy by studying patients.

In this study, scientists from Germany & Belgium reviewed 76 cases of adult-onset nemaline myopathy, and here’s what they found:

1/ The average age of patients who begin seeing symptoms is 52 years old.

2/ In about half of all patients, another disease called monoclonal gammopathy of unknown significance (MGUS) was also observed.

3/ Doctors treat these patients in several ways, but peripheral blood stem cell therapy was the most successful treatment for adult-onset nemaline myopathy patients that also had MGUS.

I have my Google alert on for nemaline myopathy; as soon as new information is released, I’ll report on it again.

⬇️ Explore Other Popular Stories ⬇️

• CRISPR, Dorian Gray, and the Future of Youthfulness - Read Now 

• Measles to Kill Medulloblastoma - Read Now

• Complexity Challenges Progress in Autism - Read Now

• Preventing AML Relapse with Cell Engineering - Read Now

• TALENs as Targeted Therapy for HPV-Induced Cancer - Read Now

Submit a request to our team for a specific disease. 

Disclaimer

The information provided on this platform is for educational and informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment. We do not provide medical advice; nothing on this platform should be construed as such. The information provided on this platform is based on scientific research and is intended to provide users with a general understanding of various medical conditions, treatments, and preventative measures. However, the information provided is not comprehensive and should not be relied upon as a sole source of medical advice. You should always seek the advice of a qualified healthcare provider with any questions or concerns you may have regarding a medical condition. Never disregard professional medical advice or delay seeking it because of something you have read on this platform. We do not endorse any specific tests, physicians, products, procedures, opinions, or other information that may be mentioned on this platform. Reliance on any information this platform provides is solely at your own risk.

x