New Gene Therapy Trial Shows Promising Results for Alpha-1 Antitrypsin Deficiency Treatment

There's exciting news for people with Alpha-1 Antitrypsin Deficiency, or AATD. Scientists have positive initial data in finding a way to fix the problem that causes this disease. A new therapy called BEAM-302 has shown positive results in early testing, which is a major achievement.

The Milestone: First Clinical Genetic Correction

Last March, a company called Beam Therapeutics announced good news about their BEAM-302 therapy. This is the first to show that it can accurately change the genetic mutation causing AATD in patients.

This is an important achievement because it’s the first-ever clinical genetic correction to treat a disease-causing mutation of AATD. The goal is to help the body produce the alpha-1 antitrypsin protein the way it should again.

What’s Alpha-1 Antitrypsin Deficiency?

To understand why this news is a milestone, you need to know first what Alpha-1 Antitrypsin Deficiency is. AATD is a condition caused by low levels of alpha-1 antitrypsin (AAT) protein. Your liver produces this protein to protect your lungs from damage caused by enzymes like neutrophil elastase.

In AATD, you have unusual alpha-1 antitrypsin levels in your body. Instead of being released into your bloodstream, AAT gets trapped in your liver cells. When that happens, it raises your risk of getting lung or liver disease. This condition also runs in the genes and can be inherited from your parents. 

What Are the Symptoms?

The symptoms of AATD vary. Some people are not even aware they have it. For those who do, they usually experience these symptoms at 20 and 50 years old:

• Shortness of breath (dyspnea)
• Wheezing
• Chronic bronchitis
• Emphysema
• Liver disease (cirrhosis, hepatitis)
• Panniculitis (painful skin lumps)

It is quite common for people to get diagnosed first with asthma because wheezing is one of its symptoms. Patients who have AAT deficiency also respond well to asthma medicines.  

Diagnosing AATD

AAT deficiency is a complicated health condition. Smoking is one of its common factors, and some are still unclear. What’s more interesting is that even if you have two broken AAT genes, you might not show any symptoms.

There are multiple ways to diagnose this disease. First, it involves a blood test to measure alpha-1 antitrypsin blood levels. If it’s lower than normal, you’re likely to have AATD. Mito Health offers a comprehensive blood panel to check over 100 biomarkers, including lung and liver biomarkers.

To confirm the blood panel results, genetic testing is used to pinpoint if you have specific gene mutations. Lastly, a pulmonary test is done to check if your lungs are working properly. Other tests also include liver function tests and imaging.

Current Alpha-1 Antitrypsin Deficiency Treatment

Unfortunately, there is no cure for AATD. The AAT deficiency treatments available today focus on managing the symptoms and try to slow down lung and liver damage. Other treatments also include giving people infusions of the missing AAT protein.

Certain lifestyle changes, like quitting smoking, are very important in treating AATD. And in very severe cases, you might need a liver or lung transplant.

Because there's no cure, the ongoing trials of BEAM-302 are a big step forward. This new therapy aims to fix the root cause of AATD by correcting the broken gene. If successful, this could go beyond just managing symptoms and might provide a way to treat the disease itself.

How the BEAM-302 Therapy Works?

The BEAM-302 therapy is currently being tested in a clinical trial to see how safe and effective its dosages are for AATD treatment. This therapy uses a unique approach by targeting the root cause of the disease: the liver. It uses lipid nanoparticles (LNPs) to send the gene-editing tools straight to the liver cells.

Around 100,000 individuals in the U.S. carry two copies of the Z allele, known as the PiZZ genotype. But, only about 10% of these patients are believed to have been diagnosed with AATD. 

Now, the BEAM-302 therapy focuses on fixing a genetic mistake known as the PiZ mutation, which causes severe AATD. It uses a technique called base editing. Basically, it makes a tiny, targeted change to the DNA to swap an "A" for a "G" in the genetic sequence.

BEAM-302 is working on fixing the PiZ mutation, and it has some important goals:

1. Reduce the buildup of the faulty AAT protein in the liver, which can cause a lot of harm.
2. Help the liver create normal, healthy AAT protein again to protect the lungs.
3. Lessen lung inflammation by getting rid of the faulty AAT protein in the blood.

Instead of just adding more AAT like other treatments, BEAM-302 helps your body produce its own healthy AAT protein. It’s designed to boost AAT production when you're feeling unwell or have inflammation, similar to how healthy people do it naturally. Plus, the genetic correction is meant to last a long time.

This clinical trial checks if BEAM-302 treatment is safe. They want to see if it can fix the PiZ mutation and increase AAT protein levels. They’ll also keep an eye on patients’ lung and liver health to understand how the treatment impacts their overall well-being.

A Future of Possibilities

The positive results from the BEAM-302 trial are an important step forward for people with AATD, especially for patients with the PiZM genotype. This specific variant comes with a moderate risk of lung and liver issues linked to AATD.

This news is hopeful for people diagnosed with AATD. Some of them are unsure about their health condition, while others have limited options beyond just managing symptoms and making lifestyle changes. 

While more research and clinical trials are still needed to ensure the safety and effectiveness of this new treatment, it’s promising to think that PiZM carriers might finally have a solution that addresses the root cause of their condition, rather than just the symptoms.