Poliomyelitis is a crippling and potentially fatal disease caused by a virus. As recently as 60 years ago, there were few diseases more frightening to parents of young children than polio. Today, polio cannot be cured. It is extremely rare, however, because it is safely and effectively prevented by vaccination.

With the poliovirus edging closer to eradication across the globe, Southern Research’s infectious disease labs are playing a critical role in the search for a drug that could aid the ongoing worldwide polio eradication initiative and help halt the spread of the crippling disease in a future outbreak or bio-attack.

Under a contract with the National Institute of Allergy and Infectious Diseases (NIAID), Southern Research scientists in Frederick, Maryland, are screening compounds that could prove useful against polio, as well as a related virus, coxsackie. Coxsackie virus infection is a leading cause of both acute and chronic myocarditis for which there is currently no effective treatment or vaccine.

The ultimate goal of the work is to identify a broad spectrum anti-viral agent that could be developed as a therapy to treat the highly contagious poliovirus and address the unmet medical need for an effective antiviral against coxsackie virus disease.

“Developing an anti-viral drug against polio is part of the strategy to mitigate risk associated with post-eradication exposure events, be they accidental or an intentional exposure resulting from a bioterrorist attack,” said Mike Murray, Ph.D., director of government business development for Southern Research’s Drug Development division.

“Once poliovirus is declared eradicated, the population may become more vulnerable to an outbreak because of potential changes in vaccine requirements and the rising number of parents refusing to vaccinate their children because they don’t see the need for it,” Murray added.

Moreover, Global Polio Eradication Initiative (GPEI) activities for 2013-2019 require approximately $7 billion to complete. “In this context, the reason to develop an antiviral is very simple – protect the multibillion-dollar investment made to eradicate polio,” said Murray, who previously headed infectious disease research for Southern Research in Frederick.

SEEKING A THERAPY

Southern Research’s Frederick labs have been involved in this effort with NIAID support since 2012. Murray said he’s optimistic that drug development efforts will produce a therapy against polio, though he notes bringing a drug to market is a costly process that typically takes years. Regardless, having an anti-viral drug effective against polio would be valuable, he added.

“Many people think polio is not a problem – it’s gone,” Murray said. “It’s not.”

Polio reemerged in Syria in 2013, and there were outbreaks in Somalia that year as well. Poliovirus is still circulating in Afghanistan and Pakistan, with 19 cases reported so far in 2016.

“We are involved in the strategic end game now, helping to solve one of the world’s most difficult problems, so that’s exciting. This contract is part of that,” Murray said.

REDUCING THE TOLL

Polio, or poliomyelitis, affects the central nervous system, sometimes producing paralysis. Between the late 1940s and early 1950s, polio crippled around 35,000 people each year in the United States alone, many of them children. The viral infection earned a fearsome reputation during this period.

Since then, vaccines have dramatically reduced polio’s human toll. The World Health Organization says polio cases across the globe have decreased by more than 99 percent since 1988, from more than 350,000 cases to 359 reported cases in 2014.

There are still two countries, Afghanistan and Pakistan, with endemic circulation of wild type poliovirus, and, recently, two children have been paralyzed by the disease in Nigeria after seeing no cases there for two years, said Eun Chung Park, Ph.D., NIH program officer and contract officer’s representative for the contract.

Since 2014, there have been isolated outbreaks associated with war-torn areas of the world, where vaccination is difficult or impossible, and the virus might travel with fleeing refugees.

The Bill & Melinda Gates Foundation, which has named polio eradication one of its key objectives, says the fight to end polio continues, often under some of the world’s most difficult and dangerous circumstances. It has vowed not to give up until every last child is protected.

INEVITABLE ERADICATION

Murray said polio’s eradication is inevitable, but it will not be easy. Poliovirus will become the third virus to be wiped out after a global campaign. The others are the smallpox virus, an ancient pathogen responsible for the deaths of hundreds of millions of people, and rinderpest, also known as the “cattle plague.”

As with the victory over small pox, however, there are fears that polio could make an unexpected comeback. To mitigate the risk associated with the reemergence of poliovirus, scientific research, vigilant surveillance, vaccine manufacture and new product development will continue.

The government is looking for drugs that will aid in the final eradication process and at the same time preparing for accidental exposure or nefarious use as a weapon. That’s where Southern Research contributes, Murray said.

“Poliomyelitis is still a risk. You could imagine a situation similar to measles where people become complacent or worse, refuse to vaccinate their children,” Murray said. “Then all of the sudden, there’s an outbreak. We saw this in the Disneyland measles outbreak last year. The outbreak spread to Disneyland and then to seven states and two other countries due to the virus being carried by travelers to and from the theme park.”

TARGETING COXSACKIE

Coxsackie, the other target in Southern Research’s NIAID contract, is a leading cause of both acute and chronic myocarditis, an inflammation of the middle layer of the heart wall. Coxsackievirus can also cause pancreatitis, an inflammation of the pancreas.

Today, there is neither a vaccine nor a therapeutic treatment for this viral infection.

Like polio, coxsackie is an enterovirus, a group of single-stranded RNA viruses associated with a wide range of human diseases. Taken together, the screening performed by Southern Research’s infectious disease labs provides a means to evaluate broad-spectrum therapeutics against enteroviruses.

NOTE: This project has been funded in whole or in part with federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under Contract No. HHSN2722010000221.