UCLA-led team receives $3.5 million NIH grant to develop treatment for mpox: What to know about the viral illness

Researchers from the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA have received a $3.5 million grant from the National Institutes of Health to study and develop treatments for the infectious disease mpox.

The five-year grant was awarded to principal investigator Dr. Vaithilingaraja Arumugaswami, professor of molecular and medical pharmacology at the David Geffen School of Medicine at UCLA, with collaborator Robert Damoiseaux, director of UCLA’s Molecular Screening Shared Resource, and co-principal investigator Ashok Kumar, professor of ophthalmology, visual and anatomical sciences at Wayne State University School of Medicine.

Mpox is a viral illness caused by infection with mpox virus, formerly known as monkeypox virus. It produces flu-like symptoms and lesions that can spread across the body and sometimes infect the eyes. In 2022, an mpox outbreak led to more than 100,000 cases worldwide, including over 32,000 in the U.S. 

While cases fell in many areas in 2023, new outbreaks surged again the following year, particularly in the Democratic Republic of Congo and surrounding countries — where a newer, more virulent strain has led to increased deaths, especially among children.

Although only a handful of cases from this newer strain have been reported in the U.S. so far, primarily in travelers, experts say the virus is rapidly evolving in ways that could eventually make it far more dangerous and widespread. 

With this new grant, the UCLA-led team will work toward three goals: 

• Understanding how mpox virus spreads and causes injury within skin and eye tissue through studies using human stem cell-based models.
• Identifying the genetic mutations that are making newer strains of mpox virus more infectious and lethal.
• Developing new classes of antiviral drugs to treat mpox infection and stop viral transmission.

Arumugaswami and two members of his team — staff scientist Anne Zaiss and research associate Arjit Vijey Jeyachandran — share why this moment in mpox research may be a tipping point and how their discoveries could help prevent the next global outbreak.

What do we know so far about the new strain of the virus, and what are you seeking to learn? 

When the virus was first detected in humans in the 1970s, infections mostly occurred through contact with infected animals. Then it evolved to be able to spread from human to human. 

Over the past three years, the virus has rapidly evolved into different strains that can spread more easily between humans. While much of the 2022 outbreak involved sexual transmission and intimate contact, the strain spreading most widely now can transmit through close personal contact of many kinds — for example, sharing linens or simply caring for sick children. Alarmingly, children are particularly vulnerable to this strain. 

We’re studying the genetic changes that have enabled these new strains to do better at evading the immune system. Understanding these mutations is essential for developing effective drugs and vaccines before the virus spreads further.

Why focus on developing antiviral drugs — wouldn’t vaccines be enough?

Vaccines are the best defense against viruses, but there are no available vaccines designed specifically against the mpox virus. There are two vaccines against smallpox that have been found to provide a good degree of cross-protection against mpox. However, there isn’t widespread access to vaccines in the countries hardest hit by the current outbreaks. 

Antiviral drugs provide another essential tool, especially for people who are already infected. Small-molecule drugs are often faster and cheaper to manufacture and distribute than vaccines and can help infected people clear the virus and prevent them from spreading it to others, limiting the virus’s ability to evolve further.

Have you identified any promising drug candidates so far?

Yes — and we’re very excited by what we’re seeing.

With help from Dr. Damoiseaux, our team screened thousands of compounds and identified several that block mpox virus replication very effectively. What’s especially interesting is how these drugs work.

Most DNA viruses that infect humans replicate inside the nucleus of our cells, but mpox virus is unusual: It replicates in the cytoplasm, outside the nucleus. Our cells are designed to recognize foreign DNA in the cytoplasm as a danger signal, using a pathway known as cGAS-STING to trigger an immune response.

The newer strains of mpox have evolved to shut down this STING protein more efficiently, allowing the virus to fly under the immune system’s radar. But one of our lead drug candidates turns STING back on — essentially restoring the cell’s natural defense response.

In mouse models of mpox infection, this drug candidate efficiently blocked viral replication without any toxicity. 

What are the next steps in developing this drug?

This NIH grant will allow us to take these promising findings from mouse studies into human tissue models.

We’re collaborating with Dr. Kumar, who is using limbal stem cells from donated human corneas to grow eye tissue in the lab and is contributing to the development of an ocular mpox mouse model. With these models, we can study how the virus infects the different cell types found in the eye and test whether our drug can stop the infection from spreading in this highly sensitive area.

We’re also testing the drug in stem cell-derived human skin organoids — essentially miniature lab-grown skin tissues that mimic the structure and function of real human skin. If these studies are successful, we hope to approach the FDA next year to begin discussions about IND-enabling (investigational new drug) preclinical studies essential for human clinical trials.

Why is it important for the U.S. to invest in mpox research if it’s not widely spreading here right now?

Because viruses don’t stop evolving just because we stop paying attention.

Mpox virus has already demonstrated an alarming ability to adapt. The longer it continues circulating anywhere in the world, the more likely it is to gain new mutations that make it even more contagious or dangerous — including here in the U.S. New mutations can potentially reduce the protective efficacy of the currently available smallpox vaccine. 

Viruses don’t sleep, they don’t take holidays and they don’t respect borders. They are constantly probing their hosts, learning new ways to infect and spread. Preparing now — with both drugs and vaccines — is far more effective than scrambling after an outbreak has already exploded.