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Researchers Explore a New Type of Therapy To Treat PAH

Posted on November 14, 2022
Medically reviewed by
Steven C. Pugliese, M.D.
Article written by
Maureen McNulty

Pulmonary arterial hypertension (PAH) occurs when blood vessels in the lungs become too narrow, making blood pressure rise. Although there is no cure for PAH, several therapies can help you feel better and keep you healthier for longer. Additionally, researchers are continuously conducting studies to learn more about this condition and to develop medications that could help treat PAH in the future.

Some members of myPHteam have expressed interest in trying new PAH therapies. “Have any of you participated in any studies for PH?” asked one member. “I am interested in being part of one that is researching another pathway.”

Another member commented, “I’m constantly researching clinical trials and possible future treatments.”

Read on for more information about the causes and treatments for PAH and a potential new treatment that’s being studied.

PAH and Its Treatments

PAH is a type of pulmonary hypertension (PH). All types of PH involve high blood pressure in the pulmonary arteries (the blood vessels that carry blood from the heart to the lungs). However, when these high-pressure levels develop because the blood vessels become too narrow or stiff, it’s known as PAH.

This high blood pressure forces the heart to work too hard to pump blood — a process that could eventually cause other heart problems like right ventricular hypertrophy (a condition in which the right side of the heart grows abnormally large) or heart failure.

Scientists are still learning about the causes of PAH. A person may develop this vascular disease when their blood vessels become injured or damaged. PAH could also be triggered by genes or medical conditions that cause changes in the proliferation (growth) or behavior of the blood vessels in the lungs, also known as vascular remodeling.

Arteries are surrounded by vascular smooth muscle cells (VSMCs). These muscle cells make the blood vessels contract and relax, helping blood to flow through. In PAH, the VSMCs grow and divide too much, thickening the layer of muscle tissue around the arteries. This narrows the arteries and increases the pulmonary arterial pressure — it causes blood to press more strongly against the walls of the blood vessels.

Some PAH treatments called endothelin receptor antagonists (ERAs) stop VSMCs from growing abnormally. Drugs in this category such as bosentan (Tracleer) and ambrisentan (Letairis) can keep the blood vessels from becoming too narrow.

Other medications for PAH may work in different ways. For example, some treatments encourage the lungs to make molecules that widen the blood vessels or relax their blood vessels.

A Possible New Treatment for PAH

Results of a recent study show that a new type of medication — a monoclonal antibody — might help people with PAH. This treatment may work in a similar way as ERAs, preventing VSMCs from growing too much. Although this treatment has not yet been studied in humans, early research looks promising.

What Are Monoclonal Antibodies?

Antibodies are immune system proteins that help immune cells recognize and destroy germs, old cells, and foreign substances.

Monoclonal antibodies are laboratory-made versions of these proteins. They can be designed to recognize different types of cells or proteins within the body. Monoclonal antibody treatments are used to treat many diseases, including cancer, COVID-19, and inflammatory conditions.

Monoclonal Antibodies and PAH

Over the past few years, researchers have studied several monoclonal antibodies that could help treat PAH. For example, Chinese researchers created a monoclonal antibody called getagozuab that blocked a protein called endothelin receptor A (ETA). The ETA protein makes muscle tissue within blood vessels thicken and narrow, and getagozumab may help prevent this from happening.

Researchers in the United Kingdom developed a monoclonal antibody inhibitor that targets a different protein, osteoprotegerin. This protein is often found at high levels in people with PAH, where it is also involved in triggering the growth of VSMCs surrounding blood vessels. When osteoprotegerin was blocked using a monoclonal antibody, blood vessels grew more normally.

Both of these monoclonal antibodies were tested in preclinical studies (research using animals with PAH or cells grown in petri dishes) but haven’t yet been studied in humans.

Researchers are also using clinical trials to test whether other monoclonal antibodies and similar therapies can help humans with PAH. Clinical trials help researchers measure how effective a new treatment plan is and determine whether it is safe. Currently, two different ongoing studies are analyzing how imatinib (Gleevec), a tyrosine kinase inhibitor (TKI) used to treat certain types of cancer, may work for people with PAH.

A New Study

In a May 2022 study published in Science Translational Medicine, researchers did two important things: They learned more about one of the processes behind PAH, and they created a monoclonal antibody that could block this process.

The researchers discovered that a protein called NOTCH3 was involved in the pathogenesis (disease course) of PAH. NOTCH3 encourages the growth of the VSMCs that surround blood vessels in the lungs. NOTCH3 can be turned on and off with other proteins called ligands.

The study showed that people with PAH have too much of one ligand that activates NOTCH3 and too little of another that turns off the effects of NOTCH3. As a result, NOTCH3 causes the outer muscle layer of the blood vessels to grow and thicken.

Next, the researchers designed a monoclonal antibody that could prevent NOTCH3 from being activated. When they studied this new drug in rat models with PAH, they found that VSMCs grew normally and symptoms of PAH disappeared. Additionally, there didn’t seem to be any side effects.

This monoclonal antibody will need to be further studied in randomized clinical trials. Additional studies will help researchers learn whether the medication is as effective in humans, determine which concentrations of the drug are needed to treat PAH, and make sure it’s safe.

Accessing the Latest Treatments

If you’ve recently been diagnosed with PAH, or if your current treatment plan isn’t working as well as you would like, you may want to visit a PAH expert. A health care provider who specializes in this area will likely know about the newest therapy options.

“I met with a PAH specialist and I feel so much better,” said a myPHteam member. “He actually is working with a research team on PAH.”

To find a PAH specialist, you can ask your current doctor for a referral. Additionally, the Pulmonary Hypertension Association’s website has a map of accredited PH Care Centers located around the U.S.

To participate in a PAH clinical trial, ask your doctor or inquire at a nearby medical center. Doctors and clinics that specialize in the treatment of PAH are often good resources for clinical trials.

“I am changing from my pulmonologist to a pulmonary hypertension clinic with a specialist that understands my disease,” wrote one member. “Plus, they do trials and studies on new medication and procedures.”

Some myPHteam members have had good experiences while participating in studies. “Since I started the clinical trial, I am finally starting to gain a bit more stamina,” a member commented.

Talk With Others Who Understand

On myPHteam, the online social network for people with pulmonary hypertension and their loved ones, more than 48,000 members come together to ask questions, give advice, and share their stories with others who understand life with pulmonary hypertension.

Which therapies do you use for PAH? Are you interested in trying new treatments? Share your experience in the comments below, or start a conversation by posting on your Activities page.

All updates must be accompanied by text or a picture.
Steven C. Pugliese, M.D. is affiliated with the Hospital of the University of Pennsylvania in Philadelphia, serving as the director of the pulmonary embolism response team, co-director of the comprehensive pulmonary embolism program, and an assistant professor of clinical medicine. Review provided by VeriMed Healthcare Network. Learn more about him here.
Maureen McNulty studied molecular genetics and English at Ohio State University. Learn more about her here.

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