ANGPTL4 - a promising target protein for treating ARDS


ARDS, or Acute Respiratory Distress Syndrome, is a severe illness that affects millions of people worldwide. The condition can be life-threatening, and currently, there are limited treatment options beyond respiratory care. Masoumeh Motamedi, the project leader for Lipigon's ARDS project, provides an update on the project's status and shares the latest research in the field.

Masoumeh Motamedi is a senior researcher and the project leader for the ARDS development project at Lipigon. She holds a doctorate in physiology and has extensive expertise in ANGPTL4, a protein that plays a crucial role in regulating inflammation and lipid metabolism in the body.

"Studies have shown that ANGPTL4 levels in the blood plasma and lungs of ARDS patients are linked to the severity of the disease and chances of survival. Promising animal studies suggest that by blocking ANGPTL4, lung function can be improved, and inflammation and tissue damage caused by infections or injuries can be reduced. At Lipigon, we are experts on ANGPTL4, and we have a deep understanding of the protein's properties and how to work with it," says Masoumeh Motamedi.

ARDS: a serious and often deadly condition

ARDS, or Acute Respiratory Distress Syndrome, is a severe medical condition that can be life-threatening. It affects about ten percent of patients admitted to intensive care units and has a high mortality rate, ranging from 38 percent to up to 50 percent in severe cases.

ARDS occurs when the lungs are damaged, often due to lung inflammation, sepsis (blood poisoning), aspiration, pancreatitis (inflammation of the pancreas), or trauma. The damage can lead to respiratory failure, where the lungs can't transfer sufficient oxygen to the body's tissues.

Promising results in preclinical studies

The ARDS project is one of Lipigon's four active projects and shares the target protein ANGPTL4 with Lipisense®, the company's most advanced project currently undergoing clinical trials. Lipigon has deep knowledge of ANGPTL4 from its work with Lipisense®, which can be leveraged to develop a potential treatment for ARDS.

Read more about ANGPTL4 in an interview with Dr. Sander Kersten, a world-leading authority in the field and Lipigon's scientific advisor.

According to Masoumeh Motamedi, the ARDS project has shown promising results in preclinical studies.

In preclinical disease models, we have with a specific type of treatment consisting of an ANGPTL4-specific ASO, obtained promising results by blocking ANGPTL4 in the lung.

It appears to reduce lung damage caused by chemical injury or bacterial and viral lung inflammation in mice. The treatment was administered after the damage had occurred, indicating that the treatment seems to have a therapeutic effect, not just a preventive one," she explains.

An ASO (antisense oligonucleotide) is a short sequence of DNA/RNA that binds complementary to a specific mRNA sequence in a gene, thereby preventing cells from producing a protein. In this case, the ASO inhibits the production of the ANGPTL4 protein. "Our next focus will be to demonstrate that we can administer the ASO treatment directly to the lung. We will also investigate the mechanism of action and any potential side effects. These steps are crucial before we can proceed to clinical trials and potentially offer the treatment to patients who may benefit from it," says Masoumeh Motamedi.

Challenges in developing a successful ARDS treatment

JThe quest for effective drug treatments for ARDS has been ongoing for over 50 years, but despite many well-designed studies, results are still pending. According to Masoumeh Motamedi, this could be due to several factors. Among these, the varied causes and mechanisms behind lung damage may play a role, as well as the different treatment methods used for the condition.

"ARDS is not a simple syndrome with a single cause and treatment, but rather a complex condition that requires subcategorization and individualized treatment approaches. Drug treatments that have failed to treat all ARDS patients have shown positive effects when applied to specific subgroups," she says.

In 2021, there were over a million cases of (ARDS in the US, France, Germany, Italy, Spain, UK, and Japan (the seven major markets (7MM)), and the number of cases increases each year. In the US alone, approximately 190,000 cases of ARDS are diagnosed annually, but there are currently no FDA-approved drug treatments for ARDS. Therefore, a promising new treatment for this disease could have a significant impact on patients' lives.

ANGPTL4 – A promising target protein for ARDS treatment

According to Masoumeh Motamedi, the target protein ANGPTL4 is a promising avenue to successfully treat ARDS. There is strong evidence that blocking the protein can be an effective treatment that potentially benefits a broad spectrum of ARDS patients, regardless of the disease's origin or cause.

"By focusing on this protein, we aim to reduce vascular leakage and improve lung function, which is helpful even in severe cases of ARDS, regardless of the disease's cause. We collaborate with research groups in China and Singapore that are investigating ANGPTL4's mechanisms in acute respiratory indications. We are very excited about the progress we have made so far and see significant potential in this research area," says Masoumeh Motamedi.

Lipigon is working with traditional small molecules, gene therapy, and RNA drugs in its four development projects.

Read more about the company's approach in an interview with CEO Stefan K. Nilsson.

Read more about Lipigon's projects:

P1 Lipisense
P2 Lipodystrophy
P3 Dyslipidemia