Year: 2016

National Cancer Institute awards major contract to Southern Research

Posted on November 28, 2016

Southern Research has been awarded a new, five-year Indefinite-Delivery Indefinite-Quantity (IDIQ) contract from the National Cancer Institute to investigate the pharmacokinetic properties of antitumor and other therapeutic agents of interest to the Division of Cancer Treatment and Diagnosis (DCTD) under NCI contract HHSN261201600021I.

Southern Research NCI contract
Bernard Ntsikoussalabongui and Katie Isbell of the Drug Development division study results in a Southern Research lab.

RFP number N02CM67000-11 was issued under full and open competition, which resulted in five IDIQ awards. Task orders will be competed among the five IDIQ Contractors in the award pool and placed off of the IDIQ as requirements arise.

This IDIQ contract is one of three long-term contracts the Birmingham-based organization holds with the NCI to support its objective of developing compounds against cancer and other diseases.

“Southern Research has been working with the NCI for over 30 years with one goal in mind: helping advance the pipeline of potential drug candidates so the NCI can move forward with clinical trials,” said Sheila Grimes, D.V.M., Ph.D., D.A.C.V.P., pathology program leader and principal investigator on the project for Southern Research.

KEY ANALYSIS

Pharmacological testing is an integral part of the drug discovery and drug development processes. In order for clinical trials to commence with a candidate compound, researchers must first answer questions pertaining to how the drug interacts with, and exists within, the human body.

To accomplish this goal, Southern Research will employ a number of tests to explore in vivo tumor models and analyze the bioanalytic makeup of the compound. Under the scope of the contract, the organization is tasked with evaluating how the sample drug moves through a living system and analyzing the amount of time required for candidate compounds to break down within a system, or under a range of conditions.

“Southern Research has worked closely with the NCI for more than 30 years, and we are proud to continue those efforts in this program defining the pharmacokinetics of the next generation of anticancer medications,” said Art Tipton, Ph.D., president and CEO of Southern Research.

“The trinity of government, industry, and nonprofit research organizations like Southern Research is a necessary collaboration to enable most drugs to reach the market. We’re pleased to continue our role, and I commend our team for their ongoing extraordinary work in the field.”

Southern Research awarded $500,000 U.S. Department of Commerce grant to expand medical device innovation and commercialization

Posted on November 17, 2016

Southern Research announced today that the Alliance for Innovative Medical Technology (AIMTech) has won a grant from the U.S. Department of Commerce to expand its proof-of-concept program.

The $500,000 award is part of nearly $15 million in funds that have been allocated across 35 organizations in 19 states to create and expand cluster-focused, proof-of-concept and commercialization programs, and early-stage seed capital funds through the Economic Development Administration’s Regional Innovation Strategies program. The grants are broken into two categories, the i6 Challenge and the Seed Fund Support Grants, with AIMTech being a winner in the i6 group.

AIMTech is a collaboration between Southern Research and the University of Alabama at Birmingham (UAB) that was formed in 2014 to build a medical device community in the Birmingham region that can develop, prototype, and commercialize medical device technologies.

This grant will allow AIMTech to build upon and accelerate the momentum gained in its first two years of providing a connection between health care need and engineering solutions in medical devices.

AIMTech Southern Research Hergenrother
Robert Hergenrother is director of AIMTech.

“This is a win for the Birmingham community,” said Robert Hergenrother, Ph.D., director of AIMTech and Southern Research’s director of medical technology development. “Led by U.S. Senator Richard Shelby, I would like to thank all of the federal, state, and local elected officials in Alabama who supported us in this effort.

“These funds will let us continue to make significant progress toward commercializing inventions by focusing on idea development, customer discovery and market validation, and prototyping through our regional connectivity to Birmingham’s world-class medical knowledge, precision engineering, manufacturing, and commercial assets,” Hergenrother added.

FILLING UNMET NEEDS

AIMTech’s regional network of collaboration with its strategic partners is growing, with active support from healthcare systems such as Children’s of Alabama, St. Vincent’s Health System, and American Sports Medicine Institute. Along with UAB, these institutions make up the significant portion of the greater Birmingham medical community.

Additional assistance and support of AIMTech’s efforts continues to come from various leading business voices in the community, such as the Economic Development Partnership of Alabama and the Birmingham Business Alliance.

“The AIMTech Proof of Concept Center fills an unmet need in the Birmingham region to provide expertise, tools and resources to entrepreneurs and clinicians as they look to turn their medical technology ideas into reality,” said Greg Canfield, secretary of the Alabama Department of Commerce. “This award will help expand AIMTech’s reach in the Birmingham region, benefiting healthcare providers, entrepreneurs, and ultimately, patients.”

The vision for AIMTech’s proof-of-concept center is to ultimately be part of a regional medical device commercialization center that can assist and enable regional medical device ideas to be brought from concept to clinic, involving investors, regional colleges, startup companies and commercial partners.

With a mission statement that mirrors the i6 Challenge project outputs of innovation, regional connectivity, and commercialization of research, AIMTech is determined to grow its capabilities and make the greater Birmingham area an international center for medical device research and development.

AIMTech unveiled its first product, a force-induced treadmill called the ResistX, earlier this year.

NIH orders High Throughput Screening for Zika

Posted on November 7, 2016
High Throughput Screening for Zika
Working with assays in Sourthern Research’s High Throughput Screening lab.

In 2014, Southern Research received funding from the National Institute of Allergies and Infectious Diseases (NIAID) through a multi-center U19 grant (U19AI109680) administered by the University of Alabama at Birmingham to conduct high throughput screening (HTS) against six disease-causing viruses: dengue, West Nile, SARS, influenza, Venezuela equine encephalitis complex, and chikungunya. With the program in place, and as Southern Research has completed screening the viruses, the National Institutes of Health (NIH) issued a supplementary $650,000 award for the Birmingham-organization to expand its program to include high throughput screening for Zika.

“Southern Research has a long history in antiviral research, including screening viruses in the same flavivirus genus as Zika, so we’re pleased the NIH saw fit to expand the U19 program to include screening on Zika,” said Bob Bostwick, Ph.D., director of the High-Throughput Screening Center at Southern Research. “For drug discovery purposes, we hope to identify compounds that work well across this entire genus.”

According to the supplemental grant, Southern Research will construct an assay for Zika that can be conducted in HTS, and test over 300,000 compounds against the virus, a process that will take nine months.

Developing robust screening capabilities

For Southern Research, compound screening has been a part of the organization’s efforts since the mid-1950s, when researchers began manually screening anticancer drugs under a contract with the National Cancer Institute (NCI). Around this same period, the Virus Research Division began evaluating antiviral agents against a wide range of pathogenic viruses, including the herpesviruses, poxviruses, acute upper respiratory disease viruses, and mosquito-borne viruses, such as Yellow Fever virus.

By the 1960s, the early work had already shown promise. Manual screenings conducted by the viral research team had identified the compounds that led to the discovery of Ara-A, an antiviral used to treat human herpesviruses, chicken pox, shingles, human cytomegalovirus — a cause of childhood hearing loss — and a lethal encephalitis.

In the 1980s, following the emergence of the AIDS epidemic in the United States, Southern Research expanded into HIV antiviral research through a series of contracts and grants with the United States Army and the NIH. This effort involved screening compound collections consisting of approximately 20,000 samples, and developing a staff of scientists proficient in working with many infectious diseases. By the following decade, the organization’s anti-HIV screening program had become the largest in the country.

While earning a global reputation for producing high quality antiviral research, Southern Research’s screening capabilities were expanding far beyond antivirals to include screening of other infectious diseases and cancer. In the late 1990s, the organization invested in emerging HTS technologies to maintain a prominent role at the forefront of drug discovery. This involved assembling a large compound collection — consisting of over 1 million samples — and acquiring robotic platforms for automated screening, thus enabling the organization to test hundreds of thousands of compounds for each new target. Eventually, the program would become involved in the NIH Roadmap Molecular Libraries initiative, and serve as one of twelve centers in the NCI Chemical Biology Consortium.

“Southern Research’s in-house screening capabilities are unmatched by most universities and private research organizations across the globe,” said Art Tipton, Ph.D., president and CEO of Southern Research. “With our Biosafety Level 3 (BSL3) facility, an active in-house library of over one million compounds, and a wealth of institutional knowledge, our researchers pride themselves on finding chemical structures needed to develop drugs against some of the greatest global health threats.”

High Throughput Screening and drug discovery

Zika Virus
Zika Virus under high magnification.

Today, HTS is an automated process that allows researchers to rapidly test a large number of compounds in order to determine their potential use as starting points for the invention of new drugs. With time and advances in technology, the process of screening compounds has evolved significantly from the early days. However, despite these advances, some things remain the same.

“Whether you are working on an antiviral or an anti-cancer medication, the drug discovery process is incredibly complex and often starts with screening,” said Bostwick. “HTS usually requires screening hundreds of thousands of compounds to find three or four good chemical starting points for medicinal chemistry.”

With the recent expansion of its U19 program to include screening of the Zika virus, Southern Research maintains a prominent global position in antiviral research. Its work has led to the fight against HIV/AIDS — supporting the United States government and numerous drug companies in the production of many of the FDA-approved antiviral drugs currently on the market — and screening of compounds that allowed for numerous other drug breakthroughs, including several against previously drug resistant strains of tuberculosis and malaria. Yet, despite this record of success, researchers admit a cure for Zika will still take time.

“Even though we know a lot about flaviviruses, discovering and developing effective therapeutic agents may take several years,” Bostwick continued. “Just like any other project we’ve undertaken, we will use data as our guide and hope our efforts will yield results which can be helpful to the scientific community.”

Southern Research at 75: Discovering cancer drugs and extending lives

Posted on November 2, 2016

Southern Research scientists have been attacking cancer since the organization’s early days, developing successful approaches to chemotherapy, screening biological agents that kill cancer cells, and making other advances.

A key contribution to this fight involves the organization’s track record for discovering FDA-approved anticancer medicines.

“Of the 200 or so drugs currently used to treat cancer, seven were discovered at Southern Research,” Dr. Francis Collins, director of the National Institutes of Health, said in a video message to mark the Birmingham-based non-profit’s 75th anniversary in October.

Southern Research dacarbazine
Dacarbazine became Southern Research’s first FDA-approved cancer drug in 1975.

Collins noted that two of Southern Research’s cancer drugs are on the World Health Organization’s List of Essential Medicines, indicating their critical importance to oncology. They are fludarabine, a treatment for chronic lymphocytic leukemia (CLL), and dacarbazine, used against malignant melanoma and Hodgkin’s lymphoma.

“At Southern Research, we have developed seven anticancer drugs and made critical advances in basic research that have deepened our understanding of cancer,” said Art Tipton, Ph.D., the organization’s president and CEO.

“We will continue to use our deep science and development tools to work toward novel treatments for a disease that kills a half million Americans each year,” he added.

Southern Research’s first anticancer drug, dacarbazine, received FDA approval in 1975 and remained a front-line treatment against melanoma for many years. Its seventh FDA-approved drug, pralatrexate, entered the market in 2009 as a treatment for aggressive blood cancers.

EXTENDING LIVES

The road to FDA approval is long, as the timeline for pralatrexate demonstrates.

Research on drugs in this class began in the 1950s at California’s SRI International. A partnership between Southern Research, SRI and New York’s Memorial Sloan Kettering led to clinical trials on related compounds beginning in the 1980s.

SR 75th_Logo_Horz_RGBOnce pralatrexate was identified as viable clinical candidate, it was licensed to Allos Therapeutics for additional development in 2002. FDA approval for pralatrexate (brand name: Folotyn) as a treatment for peripheral T-cell lymphoma came in 2009 – six decades after the initial research began.

“We prepared and tested many compounds before finally identifying a substance that gave favorable results,” Southern Research organic chemist Robert Piper said at the time. “We are very glad our compound will help alleviate human suffering and extend lives.”

Piper’s role was to synthesize quantities of high-purity pralatexate used in preclinical investigations.

Piper was also involved in the discovery of amifostine, an FDA-approved medicine that protects patients from harmful effects associated with radiation treatment and chemotherapy.

THE ‘DREAM TEAM’

The foundation of Southern Research’s success in drug discovery was laid in the 1950s, when the organization assembled what former CEO Jack Secrist, Ph.D., has called the “Dream Team” in cancer research.

Under the overall direction of Howard Skipper, the leadership team was composed of John Montgomery, Frank Schabel and Lee Bennett, who headed the Organic Chemistry, Chemotherapy and Biochemistry departments at Southern Research, respectively.

“They worked together for many years, and together with their staff, were a very effective team,” Secrist said in an interview.

Southern Research cancer team
The Southern Research ‘Dream Team’, from left, Frank Schabel, Lee Bennett, Howard Skipper, and John Montgomery.

The Southern Research team established an efficient and effective approach to the development of potential new drugs, he said.

“New compounds were evaluated rapidly, and those with potential were subjected to more detailed evaluations as soon as possible, and compounds that had no activity or weak activity were set aside to make way for new compounds,” said Secrist, who once headed Southern Research’s Drug Discovery division.

This approach to drug discovery is still in use at Southern Research today, he added.

The contribution of Montgomery, a member of Southern Research’s cancer team for more than 40 years, was particularly significant. He was involved in the discovery of five FDA-approved anticancer drugs: lomustine, carmustine, dacarbazine, fludarabine, and clofarabine.

“This is what we all aspire to as drug discovery researchers, moving life-saving compounds from conception to clinic,” said Secrist, co-inventor of clofarabine with Montgomery.

Read a story about how clofarabine helped save the life of a teenage leukemia patient.

 

This is Part Nine of a series looking at the history of Southern Research.

Southern Research recognizes innovation with IP Awards

Posted on October 31, 2016

Southern Research honored the innovative work being conducted in its laboratories and facilities with the organization’s Intellectual Property Awards, which build on a rich legacy of scientific discovery and exploration.

Southern Research’s Scientific Technical Advisory Team selected this year’s winners based on the far-reaching benefits the work could have for society and on the potential for commercialization opportunities. The awards were announced at a special ceremony on Oct. 25.

Tipton Southern Research
Art Tipton is president and CEO of Southern Research

“The scientists and engineers at Southern Research specialize in developing creative solutions to difficult problems, and their inspired technical work moves us closer every day to cures and new medicines, cleaner energy, and much more,” said Art Tipton, Ph.D., president and CEO of the non-profit organization.

“It’s critical that Southern Research remains at the forefront of innovation in a number of fields so that we can continue to make important advances that improve and save lives,” Tipton added.

Awards were selected from a review of 29 invention disclosures from 58 contributors, and nine patent filings naming 20 inventors.

The winners of this year’s Southern Research IP Awards are:

  • Invention of the Year: Sam Ananthan, Ph.D., principal research scientist, chemistry department. Ananthan is honored for his work on the treatment of neurodegenerative diseases, memory enhancement, and an assay for screening compounds that are potentially useful in this area. This work is reflected in U.S. Patent 9,095,596.
  • Drug Discovery: Bo Xu, M.D., Ph.D., chairman of the oncology department; Rebecca Boohaker, Ph.D., postdoctoral researcher; and Mark Suto, Ph.D., vice president, Drug Discovery. The trio worked on PD1-PDL1 inhibitory peptides, a promising, and patent pending, therapeutic approach in cancer that targets an immune system checkpoint.
  • Drug Development: Stefan Richter, Ph.D., senior research scientist; and Greer Massey, Ph.D., senior project leader. They are honored for their patent pending work identifying a novel drug target for mycoplasma genitalium, an infection-causing bacterium that lives in the urinary and genital tracts of humans.
  • Energy and Environment: Corey Tyree, Ph.D., director; and Jay Renew, senior environmental engineer. Tyree and Renew developed a patent pending process for recover germanium, a chemical element used in transistors and integrated circuits, and rare earth elements, materials used in electronic devices, from flue gas wastewater pond ash.
  • Engineering: William Carter Ralph, manager, Solid Mechanics, and Kevin Bryan Connolly, Ph.D., advanced mechanical engineer. Ralph and Connolly designed a patent-pending approach for elevated temperature digital image correlation using high-magnification optical microscopy.
  • Medical Devices: Patrick Schexnailder, Ph.D., project leader at AIMTech. He designed a patent pending rabbit ear vascular access device that protects lab workers from needle sticks during procedures.
  • Special Award: Sam Ananthan, Ph.D., was honored for his 16 US Patents issued over an almost 30-year career at Southern Research.
Sam Ananthan Southern Research
Sam Ananthan, principal research scientist, was honored at the IP Awards for his 16 patents.

The work by Xu, Boohaker and Suto claimed the year’s overall top divisional honor.

‘CULTURE OF INNOVATION’

Southern Research patent activity has increased in 2016, with 14 new patent applications filed during the first 8 months of 2016, compared to seven during the same period last year.

Tom Blasey, Southern Research’s director of intellectual property, said identifying and protecting the organization’s valuable IP enhances its ability to generate commercialization opportunities.

“As an innovation-focused enterprise, Southern Research is constantly inventing and innovating,” Blasey said. “During its 75-year history, many important innovations have been made by Southern Research scientists and engineers, and this work continues today.

“To both support and recognize this culture of innovation, Southern Research honors its scientists and engineers who have submitted the most innovative invention disclosures, as well as those who have been awarded particularly noteworthy patents,” he added.

Southern Research at 75: Targeting HIV/AIDS for 30 years

Posted on October 27, 2016

Southern Research scientists joined the front lines in the battle against HIV/AIDS in 1986, not long after the deadly viral infection emerged as a terrifying new public health threat in the United States.

Southern Research HIV/AIDS
HIV infection has been blamed for 35 million deaths across the globe.

Three decades later, the Birmingham non-profit organization is deeply involved in a broad-based initiative to find a cure for HIV infection, which the World Health Organization has blamed for 35 million deaths globally.

Scientists at Southern Research’s research center in Frederick, Maryland, are working to develop and standardize testing assays that will help researchers detect the hidden remnants of HIV in patients successfully treated with antiretroviral medications.

These hiding spots are called “latent reservoirs,” and they allow the virus to lurk unseen for years even though blood tests no longer show traces of HIV. Because the virus is not eradicated from these cellular havens, it can spring back into action when drugs are stopped intentionally or unintentionally, triggering a full-blown infection.

“In the U.S. and other developed countries, because of the availability of highly effective antiviral therapies, the virus is completely suppressed, and HIV-infected people are leading essentially normal lives. However, they still harbor the virus,” said Mike Murray, Ph.D., director of government business development for Southern Research’s Drug Development division in Frederick.

“The next step in the fight against AIDS is the cure,” he added. “The question is how do you go in and get rid of the virus completely?”

 SR 75th_Logo_Horz_RGBTo support researchers searching for that cure, Southern Research is working to expand access to what’s called the Quantitative Viral Outgrowth Assay (QVOA). Though expensive and labor intensive, the QVOA is considered the most effective testing platform for HIV/AIDS researchers trying to evaluate the latent viral reservoir.

Southern Research is also working with experts in HIV latency to develop alternative assays that are quicker, more sensitive and less costly.

TARGETING VIRAL THREATS

Southern Research’s current HIV/AIDS work builds on decades of experience in the field of viral threats.

The organization’s virus research program got started in the 1950s, and early work focused on herpesviruses, poxviruses and mosquito-borne viruses such as Yellow Fever. In the 1970s, Southern Research virologists evaluated potential drugs against the Gross murine leukemia virus, a retrovirus that causes cancer in mice.

In 1986, the organization’s Microbiology-Virology department began work on a U.S. Army contract to study antiviral activity of compounds against exotic RNA viruses.

That same year, the Army and the National Institutes of Health (NIH) asked Southern Research to evaluate compounds for the treatment of AIDS, caused by the human immunodeficiency virus, a retrovirus that has RNA as its genetic material.

Before long, Southern Research was testing 1,500 compounds a year, making it one of the first laboratories outside the NIH evaluating AIDS compounds on a major scale.

The earlier testing program on the Gross leukemia virus, along with the development of new assays for large-scale screening, prepared Southern Research to greatly expand evaluation of potential HIV/AIDS compounds. Its labs were eventually testing large numbers of synthetic chemical compounds advanced for screening against the virus, resulting in around 20,000 tests annually for a decade.

Southern Research’s anti-HIV screening program became the largest in the country, and many of the AIDS treatments now on the market were evaluated through its program.

SEEKING NOVEL TREATMENTS

Southern Research HIV/AIDS
The infectious disease labs at Southern Research began working on HIV/AIDS in 1986.

Over the years, Southern Research’s efforts against HIV/AIDS have moved forward on several fronts, based on longstanding partnerships with the National Institutes of Health and other government agencies.

In 2014, the organization received a $24 million contract from the Division of AIDS (DAIDS) at NIH’s National Institute of Allergy and Infectious Diseases (NIAID) to provide drug discovery and development services that could lead to potential new drugs for the treatment and prevention of HIV infection.

Using high throughput screening, an automated process that rapidly assesses the activity of drug-like compounds, and preclinical studies, Southern Research scientists are seeking to identify and develop novel antiretroviral molecules against HIV.

Their focus is on therapeutics for novel viral targets not inhibited by current therapies and topical microbicides, which could neutralize the virus prior to infection.

The latent reservoir work now being done for DAIDS-NIAID puts Southern Research back on the front lines in the effort to prevent, treat, and find a cure for HIV infection, which produces around 40,000 new cases in the U.S. each year.

 “We are excited to be contributing to the HIV Cure Initiative,” said Murray, who previously headed infectious disease research for Southern Research in Frederick.

 

This is Part Eight of a series looking at the history of Southern Research.

Southern Research STEM Day introduces students to possibilities

Posted on October 27, 2016

Students from across the metro area visited Southern Research campuses Wednesday for a behind-the-scenes look at the innovative work being done by the Birmingham-based nonprofit’s scientists and engineers.

Southern Research STEM 2016
Benjamin Owusu, a graduate research assistant at Southern Research, works with students on STEM Day.

The 2016 High School STEM Day drew 55 teens from schools in Birmingham and Mountain Brook, all who were selected based on their interest and achievements in the fields of science, technology, engineering and mathematics.

Southern Research staff from the Drug Discovery, Drug Development, Energy & Environment and Engineering divisions participated in the event, leading various experiments and operations tours.

Students walked through the steps involved in anti-cancer drug discovery and testing, specifically synthesizing and evaluating aspirin as a treatment and determining the viability of cancer cells. They also learned how to grow and study bacteria in the lab.

In addition, they performed destructive and non-destructive tests on metal materials and observed demonstrations of power plant operations, control loop integration and flue gas treatment.

The purpose of Southern Research’s participation in the STEM Day event is two-fold, said Watson Donald, director of external affairs.

“This helps Southern Research in giving back to the community,” he said. “That’s something that’s very important to us: Engaging the community and young, budding scientists and engineers.”

It also helps to create a pipeline of future job candidates, Donald said.

“We love hiring from Birmingham and the surrounding communities. If we can get boys and girls interested in these careers, then we can help create a local talent pool and keep these students working here after they have completed their education,” he said.

VITAL LESSONS

Southern Research STEM 2016
Infectious disease expert Tim Sellati speaks to students attending Southern Research’s STEM Day.

Kirk Mitchell, director of the Corporate Work Study Program at Holy Family Cristo Rey Catholic High School, said the STEM Day event reinforces what’s happening in the classroom and also gives students a clearer vision for the future.

“Experiences like this really help students understand what they’re learning in class as it relates to a career,” he said.

One of Mitchell’s students, Quandre James, said he learned how to tell the difference between living and dead cancer cells.

The 17-year-old senior works as a front office assistant in the UAB Department of Medicine as part of his work study program. Someday, he wants to be a music engineer.

“I love technology, and this gives me more insight on the technical aspect of my future career,” he said.

Amauri Pettaway, a Parker High School junior, is planning a career as an oncology pharmacist. Pettaway, 16, said she likes the problem-solving aspect of pharmacology, and her interest in oncology is driven by the fact that so much help is needed to fight cancer.

The STEM Day activities at Southern Research gave her more confidence in her career choice.

“The hands-on experiments were really helpful,” she said. “I feel this is for sure what I want to do.”

Southern Research STEM 2016
Students participating in STEM Day at Southern Research took part in laboratory experiments.
Southern Research STEM 2016
Students participating in STEM Day at Southern Research look into microscopes during an experiment.

Southern Research project aims to prevent future polio outbreaks

Posted on October 24, 2016
The polio virus is close to eradication but fears persist it could return in future outbreaks.
The polio virus is close to eradication but fears persist it could return in future outbreaks.

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.

Southern Research at 75: Engineers assist ‘Return to Flight’ Shuttle missions

Posted on October 20, 2016

Just three months after Charles J. Camarda flew on NASA’s pivotal STS-114 Space Shuttle mission in 2005, the astronaut paid a visit to Southern Research — and he brought souvenirs.

Shuttle astronaut Charles Camarda visited Southern Research in 2005. (Image: NASA)
Shuttle astronaut Charles Camarda visited Southern Research in 2005. (Image: NASA)

STS-114 was one of the most important Shuttle missions for a simple reason: It represented the “Return to Flight” for the space agency after the tragic loss of Columbia two years earlier.

Camarda served as a mission specialist on Discovery, which covered 5,796,419 miles and circled the Earth 219 times at speeds reaching nearly 17,700 miles per hour. During the mission, the Shuttle docked with the International Space Station, and the crew tested new flight-safety procedures and damage inspection and repair techniques.

Camarda visited Birmingham on Nov. 10, 2005, to talk with Southern Research engineering teams that had helped NASA understand how the Columbia accident unfolded and worked to devise new safeguards to prevent a repeat.

To show the Discovery crew’s gratitude, Camarda presented the engineers with a Southern Research banner that had been aboard the Shuttle during the 14-day mission. He also gave them a composite containing a U.S. flag that also had flown on STS-114.

SR 75th_Logo_Horz_RGBThe visit of Camarda, an aerospace engineer who had supervised NASA test facilities, represented a special moment for the Southern Research team.

“We’ve had the opportunity to work closely with Charlie on a series of efforts prior to his selection to fly on STS-114,” John Koenig, director of materials research, said at the time. “We share a heritage in materials engineering with Charlie, making this flight even more special in that ‘one of us’ was on board.”

ACCIDENT INVESTIGATION

Southern Research's John Koenig inspects a fuel nozzle damaged on an early Shuttle mission.
A Southern Research engineering team led by John Koenig identified a serious Space Shuttle fuel nozzle problem.

Soon after the Columbia accident on Feb. 1, 2003, Koenig and the Southern Research team became heavily involved in a wide-ranging quest for answers to what had happened to the Shuttle.

NASA engaged Southern Research in multiple roles in the inquiry. The team looked into aspects of the obiter wing failure, triggered when super-heated gases entered through damaged tiles on the leading edge.

Engineers modeled the impact of the foam debris that struck the left wing’s leading edge 82 seconds after Columbia’s lift-off, causing the damage.

Impact tests were conducted on materials that could come off the launch system during lift-off: ice, insulating foam, composite materials, graphite from the booster separation system.

Southern Research engineers prepared specimens, conducted pre- and post-nondestructive evaluation, and studied damage modes. They also developed new testing techniques that avoided the release of debris from the booster separation motors.

In addition, the team evaluated whether the age of the carbon-carbon composites on the leading edge enhanced the probability of failure after repeated exposures to temperatures reaching 3,000 degrees.

The engineers also worked with teams that studied potential in-flight repairs to the Shuttle’s leading edge, such as patches, plugs, overwrap, and fillers. Astronaut Scott Parazynski acted as an adviser to the Southern Research team on this program.

‘SILVER SNOOPY’

After Discovery returned to Edwards Air Force Base in California to end STS-114 on Aug. 9, 2005, NASA didn’t mount another mission for almost another year. STS-121, launched on July 4, 2006, was considered the second “Return to Flight” mission for the Shuttle program.

On both of these missions, NASA had what it called “eyes in the sky” to record the lift-off and its climb toward orbit. High-flying WB-57 aircraft carried an innovative nose-mounted video system that allowed NASA to monitor the flight for debris impacts.

Southern Research’s Airborne Imaging and Recording System is still in use.

On STS-121, Discovery again returned to the International Space Station, and the crew continued to test new equipment for the in-flight inspection and repair of the Shuttle’s thermal protection system.

After the mission, NASA decided that the Shuttle was prepared to resume its scheduled flights.

That year, Koenig received a Silver Snoopy Award, an honor given by NASA astronauts for contributions that improve the success and safety of space flight.

 

This is Part Seven of a series looking at the history of Southern Research.

 

 

NIH director thanks Southern Research for ‘treatments, cures and real hope’

Posted on October 14, 2016

In a message to mark Southern Research’s 75th anniversary, Dr. Francis S. Collins, director of the National Institutes of Health, praised the organization’s scientists for making significant advances against cancer and other diseases.

“Since 1941, Southern Research has made advances that have helped people all across this country – in fact, all around the globe,” Collins said in a video shared with the Birmingham-based non-profit.

In particular, the leader of NIH, the nation’s chief medical research agency, noted the achievements of Southern Research’s long-standing cancer research program. The organization’s scientists played key roles in developing effective chemotherapy methods and in the discovery and development of numerous FDA-approved oncology treatments.

“Of the 200 or so drugs currently used to treat cancer, seven were discovered at Southern Research,” Collins said. “In fact, two of them – fludarabine and clofarabine – are even on the World Health Organization’s list of essential medicines.”

In addition, Southern Research has provided vital research tools and models that allowed other scientists to advance the development of cancer therapeutics, he said.

TARGETING DISEASES

While efforts to discover new oncology drugs continues at Southern Research, Collins noted that its scientists are also working on potential therapeutics for Alzheimer’s, Parkinson’s, diabetes, Lou Gehrig’s disease, and tuberculosis, among others.

At the same time, Southern Research is helping researchers around the world test new disease-fighting strategies. “The area of HIV/AIDS research has been a real standout,” he said.

Collins singled out Southern Research’s work in the field of reproductive toxicology, which seeks to prevent birth defects, and on the Zika virus, which has suddenly emerged as a serious threat to public health around the world.

Collins also responded to a letter from Southern Research CEO and President Art Tipton, Ph.D., who thanked the NIH for providing the Birmingham non-profit with more than $500 million in funding over the past three decades.

“Mr. Tipton, I want to let you, along with all of Southern Research and its supporters, know that you are indeed welcome,” Collins said. “And on behalf of the NIH and the American taxpayer, I want to thank you, Southern Research, for a tremendous return on this investment – a return measured in treatments, cures and real hope for a better future for people all around the world.

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