Tag: Drug Discovery

Southern Research breaks ground on new biotech center and campus renovations

Posted on May 16, 2022

Birmingham, Ala. – Southern Research today broke ground on a flagship biotech center that will anchor the development of 200,000 square feet of new or renovated wet lab space for life sciences. The new facility, located on the corner of Richard Arrington Jr., Blvd., and Ninth Avenue South, will double the organization’s lab space for researching infectious diseases and greatly expand its work to develop new treatments for cancer and other serious illnesses.

The new center is expected to create 150 new jobs at Southern Research and to double the institution’s annual economic impact to $300 million a year.

“This project represents a major investment in the city of Birmingham and in the great work being done by our Southern Research team,” said Josh Carpenter, Ph.D., president and CEO of Southern Research. “It builds on our strengths and puts us in a position for dynamic growth in the future.”

The Alabama Legislature included $45 million for the Southern Research building in the state budget for 2023, marking the state government’s first-ever investment in the 80-year-old campus.

“This represented an opportunity to create high-paying jobs in Birmingham and to support one of the state’s most important industries,” Gov. Kay Ivey said. “Scientific and technical innovation is a major driver of Alabama’s economic growth, and Southern Research has long been a key player in making it happen.”

Construction alone will create more than 1,100 project-related jobs and generate more than $190 million in economic activity, Carpenter said.

In addition to expanding space for research on infectious diseases like COVID-19, the new facility will allow Southern Research to ramp up its efforts to target common diseases that have a profound impact on the well-being of Alabamians and communities.

In addition to this new facility, Southern Research plans to renovate much of its campus and build new space to advance genomic diagnostics work over the next few years.

The city of Birmingham and Jefferson County have each been asked to provide funding alongside Southern Research and the State of Alabama to help accelerate this capital investment. While the contributions have not been approved at the City or the County, officials on both sides of Linn Park expressed support for the expansion.

“This is a transformational moment for Southern Research and for Birmingham,” said Birmingham Mayor Randall L. Woodfin. “As someone who benefited from a COVID-19 treatment developed with Southern Research’s experts, I am especially grateful to the scientists who work here and I’m proud to help them take their work to the next level.”

As Economic Development Committee Chair of the Jefferson County Commission, Steve Ammons called the Southern Research project yet another example of local leaders working across partisan and jurisdictional lines to benefit the entire Birmingham metro area.

“When we work together, we can do big things,” Commissioner Ammons said. “This expansion at Southern Research is an important project that will create economic ripples across this county and state.”

Ray Watts, MD, president of the University of Alabama at Birmingham and chair of the Southern Research board of directors, said the new facility will help fulfill his vision of creating a world-class biotech corridor that stretches from the UAB campus to Southern Research and Ascension St. Vincent’s Birmingham.

“Between UAB and Southern Research, we are working to ensure that Birmingham and Alabama become the biotech commercialization center of the Southeast,” Watts said. “This new facility will help us incubate new biotech entrepreneurs and attract top talent to this area. Southern Research and its vision for this center are intricately tied to the future success of Birmingham.”

Alongside the new construction, Southern Research has contracted Brasfield & Gorrie to help renovate more than 40,000 square feet of its existing campus facilities in Birmingham’s Southside. Investments include building out more vivarium space and launching a new clinical diagnostics lab.

Southern Research neuroscience lab wins grant for Parkinson’s, ALS research

Posted on July 14, 2021

A Southern Research neuroscience lab has received new federal grants totaling almost $3.9 million to advance its study of Parkinson’s Disease and other neurological diseases.

The grants from the National Institute of Neurological Disorders and Stroke include $3.3 million to study Parkinson’s and $594,000 for research related to frontotemporal dementia, a disease that is similar to Amyotrophic Lateral Sclerosis, or ALS.

Both grants will support a lab led by Rita Cowell, Ph.D., fellow and chair of the Department of Neuroscience in Southern Research’s Drug Discovery Division.

“These grants are a reflection of the excellence and dedication of our neuroscience team,” said Josh Carpenter, president and CEO at Southern Research. “They work every day to fight diseases that have devastated the lives of so many families. They are an asset to Southern Research and to our community.”

Cowell’s lab has worked for 15 years to study why brain cells die and lead to neurological diseases that cause an ongoing and often devastating decline in a person’s physical and mental abilities.

“If we can understand why these cells die, then we may be able to find drugs to interfere with that and stop the progression of these diseases,” she said.

For Parkinson’s, the lab received a five-year grant to advance its research on a molecule that may keep brain cells alive. The length and amount of the federal grant reflects the strong preliminary data that Southern Research has compiled in past research supported by the Michael J. Fox Foundation for Parkinson’s Research, the Southern Research Change Campaign and the Meyer Foundation.

The second grant will support two years of additional exploratory research about how neurons stop functioning in frontotemporal dementia and ALS, and will be led by Cowell and Kazutoshi Nakazawa, also at Southern Research.

Cowell is particularly proud that this exploratory grant builds on initial work at Southern Research that was supported by the Alabama Power Foundation. “That investment from our own community created the base that is allowing us to go to the next level,” Cowell said.

Southern Research is leading the research on both grants. Co-investigators on these grants are located at UAB, Virginia Tech and the University of Michigan.

Southern Research and Tonix Pharmaceuticals Reports Positive COVID-19 Vaccine Efficacy Results

Posted on March 25, 2021

Vaccine Candidate TNX-1800 Protected Both Upper and Lower Airways After Challenge with SARS-CoV-2, Suggesting an Ability to Block Forward Transmission

TNX-1800 is Based on a Proprietary Vaccine Platform Designed to Stimulate Long Term T cell Immunity

CHATHAM, NJ, March 25, 2021 – Tonix Pharmaceuticals Holding Corp. (Nasdaq: TNXP) (Tonix or the Company), a clinical-stage biopharmaceutical company, today announced preliminary results following vaccination of non-human primates with TNX-1800 (modified horsepox virus, live vaccine), a live attenuated COVID-19 vaccine candidate engineered to express the SARS-CoV-2 (CoV-2) spike protein. Immunogenicity and protective efficacy of single-dose TNX-1800 were assessed at two dose levels (n=4 per group). At Day 41 after the vaccination, animals were challenged with live SARS-CoV-2 through intra-nasal and intra-tracheal routes. Protection was assessed at Day 47 or six days after challenge. The research is part of an ongoing collaboration between Southern Research, the University of Alberta and Tonix.

“We are pleased that all eight animals vaccinated with TNX-1800 had undetectable SARS-CoV-2 in their upper and lower airways 6 days after challenge with SARS-CoV-2,” said Seth Lederman, M.D., President and Chief Executive Officer of Tonix Pharmaceuticals. “Today’s results are from the second phase of a study, in which TNX-1800 vaccinated and control animals were challenged with SARS-CoV-2. Last Fall, we reported that all eight of the animals manifested ‘takes’, a skin reaction to horsepox vaccination which is a validated biomarker of functional T cell immunity, and that vaccination was associated with neutralizing antibodies in each case. The positive results of the protection from live CoV-2 challenge that we are reporting today validate the capacity for TNX-1800 to protect against COVID-19, and also validate the ‘take’ after TNX-1800 vaccination as a biomarker for functional T cell immunity.”

Dr. Lederman continued, “’Take‘ is considered important because it is otherwise difficult and costly to measure the T cell response to a vaccine. Vaccines that elicit a strong T cell response, like horsepox and closely related vaccinia, have been established to provide long-term, durable immunity and to block forward transmission. Single dose horsepox and vaccinia vaccination led to the eradication of smallpox, which, like CoV-2 is transmitted by the respiratory route. In the successful campaign to eradicate smallpox, ‘take’ was used as a biomarker for protective immunity. We believe the absence of detectable CoV-2 in the upper or lower airways shows the potential for TNX-1800 to decrease shedding of virus and is consistent with decreased transmission.”

Dr. Lederman continued, “Although many successful vaccines have been put into use around the world, much remains unknown about COVID-19, its emerging variants, and the durability of current vaccines. We designed TNX-1800 as a single dose vaccine using a vector known to provide long term T cell immunity. This was originally demonstrated by the vector’s use as the backbone of Edward Jenner’s smallpox vaccine which typically provided lifetime immunity with a single dose. Moreover, by preventing forward transmission of the smallpox virus, it became a defining force in establishing herd immunity.” Dr. Lederman continued, Like Jenner’s smallpox vaccine, TNX-1800 can be scaled up for manufacturing and will not require a costly and cumbersome cold chain for distribution and storage. It will also be glass-sparing, with 100 doses filled per vial. These features, coupled with the results announced today, encourage us to advance TNX-1800 to human Phase 1 trials in the second half of 2021 when we expect to have Good Manufacturing Practice or cGMP quality TNX-1800 available.”

The Company believes the findings also demonstrate the flexibility of the horsepox vaccine platform and its capability to be tailored to other diseases of interest in military and civilian populations.

Key features and results:

STUDY DESIGN: This study of non-human primates compared TNX-1800 (modified horsepox virus encoding CoV-2 spike protein) to TNX-801 (horsepox virus, live vaccine) at two doses. Also a control group received a placebo. Each of these five groups (TNX-1800 high and low dose; TNX-801 high and low dose and placebo) included four animals.
CoV-2 CHALLENGE: At day 41 after vaccination (or placebo), each animal was exposed to SARS-COV-2 by intra-tracheal (1 x 10⁶ TCID₅₀) and intra-nasal (1 x 10⁶ TCID₅₀) administration.
DETECTION OF SARS-COV-2 in Upper and Lower Airway: Upper airway virus was studied by oropharyngeal swabs and lower airway virus by tracheal lavage using qRT-PCR to determine the number of genome copies of SARS-CoV-2 present in the samples. Six days after challenge, no (0/8) samples taken from animals vaccinated with TNX-1800 had detectable SARS-CoV-2 in either upper or lower airway samples. In contrast, all (8/8) animals vaccinated with the control vaccine TNX-801 showed infection (more than 1,000 genome copies) as did three of four monkeys vaccinated with vehicle control.
NEUTRALIZING ANTI-CoV-2 ANTIBODIES: At day 14 after a single vaccination, all eight of the TNX-1800 vaccinated animals made anti-CoV-2 neutralizing antibodies (≥1:40 titer) and, as expected, none of the eight TNX-801 vaccinated control animals, or any of the four animals in the placebo group made anti-CoV-2 neutralizing antibodies (≤1:10 titer). At 6 days after CoV-2 challenge, TNX-1800 vaccinated animals showed neutralizing antibody titers of (≥1:1280 titer). The level of neutralizing anti-CoV-2 antibody production was similar between the low and high dose TNX-1800 groups (1 x 10⁶ Plaque Forming Units [PFU] and 3 x 10⁶ PFU, (respectively). For unvaccinated animals challenged with SARS-CoV-2, neutralizing antibodies were measurable after vaccination (≥1:40 titer) that were lower and appeared later than neutralizing antibodies in TNX-1800 vaccinated animals.
TOLERABILITY: TNX-1800 and TNX-801 were well tolerated at both doses.
SKIN TAKE BIOMARKER: Further, as an expected additional outcome, all 16 animals vaccinated with either dose of TNX-1800 or the control TNX-801 manifested a “take”, or cutaneous response, signaling that the horsepox vector elicits a strong T cell immune response.
DOSE: These results support the expectation that TNX-1800 at the low dose of 1 x 10⁶ PFU is an appropriate dose for a one-shot vaccine in humans and indicate that 100 doses per vial is the target format for commercialization, which is well suited to manufacturing and distribution at large scale.
CONCLUSIONS: Together, these data show that TNX-1800 induces protection against SARS-COV-2 infection in non-human primates. These data confirm that “take” is a biomarker of protection of upper and lower airways from SARS-CoV-2 challenge, and a biomarker of immunological response to TNX-1800’s cargo COVID-19 antigen, which is the CoV-2 spike protein.
NEXT PHASE: Phase 1 human study targeted to start in the second half of 2021, following IND clearance by the FDA and the production of GMP material.

Anthony Macaluso, Ph.D., Executive Vice President, Strategic Development at Tonix Pharmaceuticals said, “In addition to their impact on the development of a COVID-19 vaccine, these data also demonstrate the utility of horsepox as a vaccine platform that can be used to address many other diseases of interest to the military and the general public. The horsepox platform has the following attributes favorable for vaccine development: strong induction of both B- and T-cell immunity; amenability to genetic modification; and the ability to express multiple genes, either alone or in combination. In addition, the horsepox vaccine platform allows for rapid scalability of manufacturing, which is a key advantage of HPXV over other platforms such as non-replicating viruses, DNA/RNA, or protein subunit vaccines.”

About TNX-1800

TNX-1800 is a live modified horsepox virus vaccine for percutaneous administration that is designed to express the Spike protein of the SARS-CoV-2 virus and to elicit a predominant T cell response. Horsepox and vaccinia are closely related orthopoxviruses that are believed to share a common ancestor. Tonix’s TNX-1800 vaccine candidate is administered percutaneously using a two-pronged, or “bifurcated” needle. TNX-1800 is based on a horsepox vector, which is a live replicating, attenuated virus that elicits a strong immune response. The major cutaneous reaction or “take” to vaccinia vaccine was described by Dr. Edward Jenner in 1796 and has been used since then as a biomarker for protective immunity to smallpox, including in the World Health Organization’s (WHO) accelerated smallpox eradication program that successfully eradicated smallpox in the 1960’s. The “take” is a measure of functional T cell immunity validated by the eradication of smallpox, a respiratory-transmitted disease caused by variola. Tonix’s proprietary horsepox vector is believed to be more closely related to Jenner’s vaccinia vaccine than modern vaccinia vaccines, which appear to have evolved by deletions and mutations to a phenotype of larger plaque size in tissue culture and greater virulence in mice. Live replicating orthopoxviruses, like vaccinia or horsepox, can be engineered to express foreign genes and have been explored as platforms for vaccine development because they possess; (1) large packaging capacity for exogenous DNA inserts, (2) precise virus-specific control of exogenous gene insert expression, (3) lack of persistence or genomic integration in the host, (4) strong immunogenicity as a vaccine, (5) ability to rapidly generate vector/insert constructs, (6) readily manufacturable at scale, and (7) ability to provide direct antigen presentation. Relative to vaccinia, horsepox has substantially decreased virulence in mice¹. Horsepox-based vaccines are designed to be single dose, vial-sparing vaccines, that can be manufactured using conventional cell culture systems, with the potential for mass scale production and packaging in multi-dose vials.

¹Noyce RS, et al. (2018) PLoS One. 13(1):e0188453

About Southern Research

Founded in 1941, Southern Research (SR) is an independent, 501(c)(3) nonprofit, scientific research organization with more than 400 scientists and engineers working across three divisions: Drug Discovery, Drug Development, and Engineering. SR has supported the pharmaceutical, biotechnology, defense, aerospace, environmental, and energy industries. SR works on behalf of the National Institutes of Health, the U.S. Department of Defense, the U.S. Department of Energy, NASA and other major aerospace firms, utility companies, and other external academic, industry and government agencies. SR pursues entrepreneurial and collaborative initiatives to develop and maintain a pipeline of intellectual property and innovative technologies that positively impact real-world problems. SR has numerous ongoing drug discovery programs, which encompass drug discovery programs to combat various forms of cancer, Alzheimer’s, schizophrenia, opioid use disorder, human immunodeficiency virus, disease, Parkinson’s, tuberculosis, influenza, and others. SR’s strong history, which includes over 75 years of successful collaborations to solve complex problems, has led to the discovery of seven FDA-approved cancer drugs—a number rivaling any other U.S. research institute. Furthermore, experts at SR are well-equipped to assist with the challenging landscapes of drug design and development technologies and market viability. SR is headquartered in Birmingham, Alabama with additional laboratories and offices in Frederick, Maryland.

Further information about SR can be found at https://southernresearch.org/

About Tonix Pharmaceuticals Holding Corp.

Tonix is a clinical-stage biopharmaceutical company focused on discovering, licensing, acquiring and developing small molecules and biologics to treat and prevent human disease and alleviate suffering. Tonix’s portfolio is primarily composed of central nervous system (CNS) and immunology product candidates. The CNS portfolio includes both small molecules and biologics to treat pain, neurologic, psychiatric and addiction conditions. Tonix’s lead CNS candidate, TNX-102 SL¹, is in mid-Phase 3 development for the management of fibromyalgia, and positive data on the RELIEF Phase 3 trial were recently reported. The Company expects interim data from a second Phase 3 study, RALLY, in the third quarter of 2021² and topline data in the fourth quarter of 2021. The immunology portfolio includes vaccines to prevent infectious diseases and biologics to address immunosuppression, cancer, and autoimmune diseases. Tonix’s lead vaccine candidate, TNX-1800³, is a live replicating vaccine based on the horsepox viral vector platform to protect against COVID-19, primarily by eliciting a T cell response. Tonix reported positive efficacy data from animal studies of TNX-1800 in the first quarter of 2021. TNX-801³, live horsepox virus vaccine for percutaneous administration, is in development to protect against smallpox and monkeypox.

¹TNX-102 SL is an investigational new drug and has not been approved for any indication.

²Pending submission and agreement from FDA on statistical analysis plan.

³TNX-1800 and TNX-801 are investigational new biologics and have not been approved for any indication.

This press release and further information about Tonix can be found at www.tonixpharma.com.

Forward Looking Statements

Certain statements in this press release are forward-looking within the meaning of the Private Securities Litigation Reform Act of 1995. These statements may be identified by the use of forward-looking words such as “anticipate,” “believe,” “forecast,” “estimate,” “expect,” and “intend,” among others. These forward-looking statements are based on Tonix’s current expectations and actual results could differ materially. There are a number of factors that could cause actual events to differ materially from those indicated by such forward-looking statements. These factors include, but are not limited to, risks related to failure to obtain FDA clearances or approvals and noncompliance with FDA regulations; delays and uncertainties caused by the global COVID-19 pandemic; risks related to the timing and progress of clinical development of our product candidates; our need for additional financing; uncertainties of patent protection and litigation; uncertainties of government or third party payor reimbursement; limited research and development efforts and dependence upon third parties; and substantial competition. As with any pharmaceutical under development, there are significant risks in the development, regulatory approval and commercialization of new products. Tonix does not undertake an obligation to update or revise any forward-looking statement. Investors should read the risk factors set forth in the Annual Report on Form 10-K for the year ended December 31, 2019, as filed with the Securities and Exchange Commission (the “SEC”) on March 24, 2020, and periodic reports filed with the SEC on or after the date thereof. All of Tonix’s forward-looking statements are expressly qualified by all such risk factors and other cautionary statements. The information set forth herein speaks only as of the date thereof.

Southern Research’s screening center searches for clues to COVID-19 treatments

Posted on July 7, 2020

Inside a high-tech laboratory at Southern Research, a team led by Robert Bostwick, Ph.D., is screening vast numbers of compound samples to identify agents that could become a new treatment for COVID-19, the disease caused by the novel coronavirus.

Bostwick is director of Southern Research’s state-of-the-art High-Throughput Screening (HTS) Center, which features advanced robotic equipment and a collection of around 750,000 compounds for rapid, accurate testing.

Since 2006, the HTS Center has screened an average of 3.3 million compounds each year in biochemical, bacterial, cell-based, and antiviral assays. The center’s scientists have been working on coronaviruses for the past six years.

Since the pandemic began earlier this year, Bostwick’s team has screened compound samples for pharmaceutical companies, biotech firms and key government agencies. It’s also screened FDA-approved drugs to see if they show potential activity against the pathogen.

Bostwick, who joined the Birmingham-based research organization in 2013 after working for AstraZeneca and other bioscience companies, talks about the capabilities of the HTS Center and how his team is making a contribution to the fight against COVID-19.

What is the goal of Southern Research’s screening program as it relates to the novel coronavirus?

The goal is to discover drugs that can be used as therapeutic treatments for COVID-19. By screening compounds in our HTS Center, we can rapidly identify those that exhibit antiviral effects against SARS-CoV-2, the virus that causes the disease.

These compounds can then be used as starting points for the development of new therapeutic agents.

If the screen identifies compounds that are already approved as drugs to treat various other diseases, they can potentially be repurposed for treating COVD-19.

What are Southern Research’s key capabilities in screening compounds as part of the drug discovery process?

Using automated robotic systems to perform testing is a key capability to enable high throughput screening. Southern Research’s HTS Center can also conduct screens that require containment of highly infectious agents and is internationally known for its infectious disease capabilities.

The HTS Center has screened over 15 million compound samples in over 50 different infectious disease assays. It currently serves as the screening core for the NIH-funded Antiviral Drug Discovery and Development Center (AD3C), based at UAB, our close collaborator on many projects.

Describe the scope of Southern Research’s activities in screening compounds against COVID-19.

Southern Research COVID-19 screening — Dr. Robert Bostwick directs the High Throughput Screening Center at Southern Research.

For the past six years we have been conducting a drug discovery effort for coronaviruses through the AD3C and have expanded that effort to include SARS-CoV-2.

In addition, we are providing screening services to several major pharmaceutical companies, over two dozen biotech companies, the Gates Foundation and the National Center for Advancing Translational Sciences, which is part of the NIH.

Since early April, we have been generating over 30,000 data points weekly in screens to identify compounds with antiviral activity against SARS-CoV-2.

How many compounds has Southern Research screened as part of its internal COVID-19 research program?

Prior to the outbreak of COVID-19, we had already screened over 305,000 compounds against SARS in support of the AD3C coronavirus drug discovery project. After the outbreak, we tested the hits from that campaign against SARS-CoV-2 and identified several compounds with antiviral effects against both viruses. We are making and testing dozens of new compounds for that program every month.

We also screened a collection containing FDA-approved drugs and late-stage clinical candidates against SARS-CoV-2 to identify drugs with potential for repurposing.

Why is ‘drug repurposing’ a smart approach in this pandemic?

It takes years to invent and bring a new drug to market. Since the safety profile of marketed drugs is already known, a drug need only be evaluated in clinical studies to determine if it can effectively treat a disease other than the one for which it is marketed.

Therefore, in a pandemic, it is much quicker to repurpose existing drugs for use in combating the pathogen as opposed to inventing an entirely new drug.

Support Southern Research’s work against COVID-19. Donate today.

Scientist Mark Suto: Southern Research intensifying therapeutic efforts to combat COVID-19

Posted on May 26, 2020

Responding to the COVID-19 pandemic, Southern Research has accelerated its drug discovery and development activities to identify and test vaccines and therapeutics against coronavirus that could save lives and help restore the nation’s hard-hit economy.

A key figure in this effort is Mark J. Suto, Ph.D., vice president of the Drug Discovery division and interim vice president of the Drug Development division at Southern Research.

Suto, who has made wide-ranging contributions to pharmaceutical research and drug discovery efforts during a 35-plus year career, has worked in large pharmaceutical companies, as well as smaller biotech and venture-backed firms.

Since joining Southern Research in 2011, Suto has engaged in multiple research collaborations spanning a diverse range of diseases and therapeutic areas, including rare and neglected diseases.

In a question-and-answer format, Suto discusses Southern Research’s multi-pronged effort to fight COVID-19, the virus causing the serious, sometimes fatal respiratory illness.

What is Southern Research doing to develop new therapies and vaccines against COVID-19?

As part of our long history with the identification of new medicines to treat life-threatening diseases such as cancer and HIV, we have channeled our resources to address the COVID-19 pandemic. For example, we are collaborating with several pharmaceutical companies to identify new research tools and vaccines. We recently announced a collaboration with Tonix, a biopharmaceutical firm, to test its vaccine candidate.

As part of a large consortium funded by the National Institute of Allergy and Infectious Diseases (NIAID) involving our partnering institution, the University of Alabama at Birmingham (UAB), we are building upon our ongoing research on highly pathogenic coronaviruses to develop new therapies. We are also working in partnership with UAB to test compounds for antiviral activity against COVID-19.

How did Southern Research begin its work?

From the onset of the COVID-19 threat, Southern Research quickly worked with the Centers for Disease Control and Prevention (CDC) and other government agencies to obtain the virus for experimental testing. Due to the nature of the virus (i.e., ability to rapidly spread and cause infection), handling requires highly specialized facilities available at Southern Research. After having obtained the virus, intense research has been initiated and is ongoing which aims to identify effective therapies.

Has Southern Research activated an internal COVID-19 program?

In addition to these activities, we established an internal research program to identify known drugs that will be effective against this new threat. In the case of combating COVID-19, speed is of the essence given wide-reaching consequences. It is well known that the development of new drugs is a costly endeavor and requires years of research. Southern Research has taken a non-traditional approach of drug discovery which could result in the identification of new therapies in a period of months rather than years.

What is Southern Research’s strategy in searching for new therapies?

Our approach, referred to as ‘drug repurposing’, consists of developing a rapid method or screen to determine whether there are already FDA-approved drugs that would be effective against COVID-19. We’ve tested more than 3,500 drugs and have identified 12 which are highly active against the virus. An interesting fact is that those that have been identified were all originally developed not as antivirals but rather for a wide range of medical conditions.

What are the next steps in this process?

Next, we need to further evaluate these drugs under several various conditions to identify those with clinical promise. Also, since all of these compounds are approved for use in people, clinical trials could be initiated very quickly.

Support Southern Research’s work against COVID-19. Donate today.

Project funded by The Michael J. Fox Foundation targets deeper understanding of neuronal death in Parkinson’s

Posted on August 23, 2019

The Michael J. Fox Foundation for Parkinson’s Research (MJFF) has awarded Southern Research scientist Rita Cowell, Ph.D., a $150,000 grant to study how certain brain cells die in Parkinson’s disease in order to gain insights that could lead to new therapeutic targets.

Cowell, a fellow and chair of the Neuroscience Department in Southern Research’s Drug Discovery division, said her investigation will classify different types of dopamine-producing neurons in the brain’s substantia nigra region and determine how vulnerable they are to cell death and dysfunction.

The impairment of these neurons – nerve cells that transmit high-speed signals to regions of the brain involved in initiating movements – and the resulting loss of dopamine, a chemical messenger, are key contributors to the symptoms of Parkinson’s disease.

Rita Cowell Southern Research Parkinson's — Technical approaches for Southern Research neuroscientist Rita Cowell’s projects involve capturing images of neurons with fluorescent light microscopy to visualize and localize gene expression to subpopulations of neurons.

To better understand why this happens, Cowell’s team aims to pinpoint the subtypes of dopaminergic neurons that are lost in brain tissue samples from Parkinson’s disease rodent models and humans who had the disease.

“Basically, we are going to use gene markers to identify and investigate whether the neurons that die in a mouse model are the same neurons that die in people,” she said.

“This could be really informative because if only one group of the neurons in the mouse matches what is going on in the human, that’s the only group we should be studying.”

Cowell said understanding the different molecular profiles of these neurons – and being able to identify which ones are most vulnerable to degeneration — could help scientists identify new pathways for therapies targeting Parkinson’s.

The neurological disorder affects an estimated 1 million . Around 60,000 new cases are diagnosed annually in the United States, typically in people over 60, according to the Parkinson’s Foundation.

URGENT NEED

Cowell said new treatments are urgently needed against the disease, which progressively slows movement, impairs speech and even leads to dementia in some patients.

“Currently, the main treatment for patients with Parkinson’s is L-Dopa. This dopamine replacement therapy can manage symptoms, but it does not slow the progression of the disease,” she said.

“What happens is that, over time, the L-Dopa becomes less effective. There is only so much the drug can do – it can’t stop cell loss.”

The grant from The Michael J. Fox Foundation is Cowell’s third from the non-profit organization.

All of these projects share the long-term goal of finding ways to prevent cell loss in Parkinson’s disease.

Cowell said funding for supplies needed to collect critical preliminary data for The Michael J. Fox Foundation grant application stemmed from donations to Southern Research’s inaugural Change Campaign in 2018. The peer-to-peer fundraiser generated a total of $200,000 to advance research projects in neuroscience, oncology and sustainable chemistry.

“This is a prime example of how we often just need seed funding to promote good ideas. We had the ideas, but we just didn’t have the resources to pursue them,” Cowell said.

“We knew there were opportunities that would allow us to secure that extramural funding. The project simply needed that little nudge, and the Change Campaign provided it.”

Southern Research is in the process of planning its next Change Campaign event to support similar projects and increase the likelihood of identifying new ways to treat disease.

Southern Research aims to speed drug discovery with 3-D bioprinting

Posted on July 25, 2019

Inside a Southern Research lab, a new 3-D bioprinter is silently stitching together a gelatin structure that mimics a human tumor, the device’s precise movements directed by a computer program’s highly detailed geometry.

In the future, Southern Research scientists will be able to use this tumor model, created with realistic three-dimensional architecture and implanted with living cells, as a revolutionary kind of testing platform to accelerate drug discovery efforts.

“Additive manufacturing technologies have the potential to improve how we develop drugs, which today is a hugely expensive process that too often fails,” said Stacey Kelpke, Ph.D., program manager for medical device technologies at Southern Research.

“With 3-D bioprinting, we can create models using human cells in a tumor that is structured just like you would see in someone’s body, increasing accuracy when drug candidates are being evaluated,” she added.

Southern Research additive manufacturing — Southern Research’s Stacey Kelpke shows Birmingham businessman Gene Robinson a computer image of an object being created by the 3-D Bioplotter. Robinson’s donation made the purchase possible.

Southern Research acquired its EnvisionTEC 3-D Bioplotter in June, thanks to a generous gift from Birmingham businessman Gene Robinson, who has become a champion of the game-changing potential of 3-D printing technologies. In further support of Alabama business, Southern Research purchased the Bioplotter from SWIGRO, an Auburn, Alabama-based company that is focused on additive manufacturing.

Robinson’s $100,000 donation was paired with $50,000 in federal grant funding to complete the purchase of the device capable of printing three-dimensional structures with biomaterials. Only a small number of the specialized devices are in use across the Southeast.

“Without Gene, none of this would have happened,” Kelpke said. “His vision will help advance drug discovery and development at Southern Research as we work to uncover new insights against a whole range of diseases and new therapies to combat them.”

OPENING NEW DOORS

Rebecca Boohaker, Ph.D., assistant fellow in Southern Research’s Oncology Department, said plans are already under way to integrate the 3-D Bioplotter into a sweeping range of future drug discovery research projects.

“We’re developing a skin model to test topical-based drugs that would protect against harmful agents that can be absorbed through the skin,” she said. “We can develop a 3-D lung model for cystic fibrosis for compound testing. That is aside from what I was initially interested in – tumor models. We can also develop 3-D models in Parkinson’s, Alzheimer’s and other diseases.”

During a recent visit to Southern Research, Robinson got an opportunity to see the 3-D Bioplotter in action, as the device meticulously built the structure of a miniature human brain, layer upon layer, in a demonstration.

Robinson, who has invested in an additive manufacturing company in Auburn, wants his gift to Southern Research to inspire other Alabama business leaders to make donations to spread the adoption of 3-D printing technology across the state. He’s also eager to see Alabama solidify its position as an emerging hub for the development of additive technologies.

“The business leaders of Alabama need to get behind this. We’re No. 1 in football, but that only goes so far. I want us to be No. 1 in additive manufacturing,” Robinson said.

Southern Research 3-D Bioprinting — Southern Research’s 3-D Bioplotter creates precise three-dimensional objects based on computer designs like this one of a miniature human brain.

Robinson, who founded the medical device company IMS in Birmingham, said he was interested in helping Southern Research acquire the 3-D Bioplotter because the device can make an impact.

“Since I sold my company in 2014, I have just been looking for something significant to do, something that can make a difference. You know, people donate to all kinds of causes, but what will make a difference? That’s what I asked myself. Then I called Stacey,” he said.

SPEEDING DEVELOPMENT

Thanks to its potential to industrialize the production of 3-D human tissues, Kelpke said bioprinting technology can help researchers address problems that have slowed drug development. The National Institutes of Health (NIH) says current methods of delivering new drugs can take decades, cost billions of dollars, and fail about 95 percent of the time.

Today, for example, researchers use 2-D cell models for testing potential drugs for activity against certain diseases, Kelpke said. But the cell-to-cell interaction can be quite different when the compound is tested in animal models. There are also issues with testing results derived from animal studies, which can be misleading or disappointing.

As a result, most drug candidates fail in clinical trials because they are shown to be unexpectedly ineffective or toxic, despite encouraging results in early testing.

To accelerate the technology’s development, the NIH’s National Center for Advancing Translational Sciences has established a bioprinting project so its scientists can develop 3-D laboratory-grown human tissue models that can be produced efficiently and at scale.

At Southern Research, Kelpke and Boohaker are assessing the full potential of the 3-D Bioplotter for the Birmingham-based organization’s Drug Discovery team.

The potential seems unlimited. In addition to realistic tumor models, Kelpke said the device could be used to print cartilage for joint replacements. It also has potential in unlocking the mystery of how to get medicines for Alzheimer’s past a barrier that blocks the path to the brain.

“For us, it’s really just imagine how you can use it, and you can build a 3-D structure and validate it,” Boohaker said.

Robinson wants his gift to Southern Research to spark a movement to make Alabama a leader in this transformational technology.

“I just hope that business leaders across Alabama will take a moment and start investigating additive manufacturing technologies and seeing how they can embrace it for their companies, how they can invest in additive companies, or how they can embrace it for the state of Alabama,” he said. “We don’t want to lose this opportunity.”

Are you interested in joining Gene Robinson as a catalyst for discoveries that will change the world? Click here to donate.

Alabama Power Foundation grant accelerates research on potential ALS drugs

Posted on May 30, 2019

A Southern Research scientist’s early-stage work on potential new therapies for amyotrophic lateral sclerosis, or ALS, is getting a push thanks to a grant that will speed the project.

Rita Cowell, Ph.D., Fellow and Chair of the Neuroscience Department in Southern Research’s Drug Discovery division, is studying compounds that in lab tests have prevented the neuronal loss that is a hallmark of ALS, a devastating condition characterized by muscle atrophy and paralysis.

The Alabama Power Foundation grant will permit her to accelerate her research into these compounds and to gather the extensive scientific data needed to apply for substantial federal funding opportunities.

“In this internal project, we’re actually working on two areas of ALS research,” Cowell said. “One is related to drug discovery, and the other focuses on understanding the biology of this debilitating disease.

“We don’t have additional resources to devote to this work, so this grant allows us to expand our studies, which have a lot of potential.”

NOVEL TREATMENTS

Rita Cowell, Ph.D., Fellow and Chair of the Neuroscience Department, is studying compounds that in lab tests have prevented the neuronal loss that is a hallmark of ALS.

ALS is a progressive neurodegenerative disease that affects nerve cells in the brain and the spinal cord, killing motor neurons in the body that control movement. It’s sometimes called “Lou Gehrig’s Disease,” after the baseball great from the 1930s.

The ALS Association says the condition, which usually strikes people between the ages of 40 and 70, affects at least 16,000 Americans at any given time. The average life expectancy of an ALS patient is two to five years from the time of diagnosis, the group says.

Cowell said there are only two FDA-approved drugs to combat the disease, and while these medicines have been shown to slow the progression of ALS, they don’t help some patients at all. That leaves them with no treatment option.

“There is a desperate need for new drugs for ALS,” she said.

Myla Calhoun, President of the Alabama Power Foundation, said the grant provided to Cowell’s team can help to deepen the understanding of this devastating disease and contribute momentum to promising drug discovery efforts.

“Health and Human Services is one of the five focus areas of the Foundation and we hope this grant will help position our state as a leader in medical research and development,” said Calhoun. “Southern Research is uniquely positioned to make progress in this area, and our grant will allow its Drug Discovery team to continue moving therapies closer to patients in need. “

CELL DEATH TRIGGER

Working in Southern Research labs, scientists have identified compounds that have the potential to counteract the cell death that is a central feature of ALS. This neuronal loss is tied to an overabundance of what is called “reactive oxygen species,” or ROS, a stress response that leads to cell death.

“Certain cells, like the motor neurons that are lost in ALS, have been shown to be sensitive to this stress response over time,” Cowell said. “The compounds we have identified could boost the ability of these neurons to counteract the stress response and protect them from cell death.”

To move the project forward, Cowell’s team will conduct key tests of the compounds in a series of cell-based assays to gauge how the chemicals work against ALS. The data could provide a pathway to government or commercial funding for tests in mouse models of ALS and eventually Phase I clinical trials.

“This drug discovery research is in its very early stages, so we don’t expect to have a lead compound in a clinical trial after one year of funding,” Cowell said. “But the grant from the Alabama Power Foundation will help us move toward our long-term goals of discovering new approaches and therapeutics to treat ALS.”

Cowell’s team in Southern Research’s Neuroscience Department focuses on the mechanistic underpinnings of why people develop neurological diseases and disorders such as Alzheimer’s, Parkinson’s, ALS, schizophrenia and depression.

Southern Research team targets new, safer drugs for malaria

Posted on May 21, 2019

Scientists at Southern Research’s Drug Discovery division have joined the fight against malaria through efforts aimed at discovering new drugs and improving the safety and efficacy of current antimalarial medicines.

A research team lead by Babu Tekwani, Ph.D., distinguished fellow and chair of the Department of Infectious Diseases at Southern Research, is working on the development of nano-formulations of drugs that prevent relapse of the illness.

This project, funded by the NIH’s National Institute of Allergy and Infectious Diseases (NIAID), targets malaria caused by Plasmodium vivax, one of the five plasmodium parasites responsible for the serious and sometimes fatal disease in humans.

Vivax malaria is notorious for causing relapses, even after treatment with commonly used antimalarial drugs.

Southern Research Tekwani — A Southern Research team led by Dr. Babu Tekwani, center, is seeking to discover new therapeutics for malaria and to make existing medicines for the disease safer.

Today, Primaquine is the only FDA-approved drug available to prevent relapses in malaria patients, eliminating all malaria parasites from the body in what is referred to as radical cure.

The medicine, however, causes severe destruction of red blood cells, a condition known as hemolysis, in individuals with the genetic deficiency of glucose 6-phosphate dehydrogenase (G6PD).

This side effect prevents the use of Primaquine in a substantial proportion of malaria-infected individuals.

Tekwani’s team at Birmingham-based Southern Research has established specific experimental models and bioassays to evaluate the safety and efficacy of drugs in G6PD deficiency. These models are being employed to test new antimalarial drugs and formulations.

Tekwani’s team is also working on a research project to better understand the molecular basis of antimalarial drugs’ action. The goal of the project is to develop new antimalarial drugs with better safety profiles and activity against drug-resistant cases of malaria.

This project is funded by the U.S. Department of Defense in collaboration with the University of Mississippi and the Walter Reed Army Institute of Research.

“The continuous emergence of drug-resistant cases of malaria underscores the need for the identification of new drugs,” Tekwani said. “Indeed, the building and continuous augmentation of an armamentarium of multiple drugs is necessary to cope with the growing problem of drug-resistance”.

“The experimental models we’ve developed for evaluation of the safety and efficacy of antimalarial drugs have provided better tools for new antimalarial drug discovery,” he added.

BATTLING MALARIA

Malaria continues to be a global health challenge despite extensive efforts initiated by global and public health agencies for malaria control. The mosquito-borne disease claimed the lives of 435,000 people in 2017, of which included mostly children in Africa. There were 219 million cases reported worldwide that year. In addition, an estimated 1,700 cases of malaria are reported in the U.S. each year.

More than 3.3 billion people in 106 countries continue to be at risk for contracting malaria, according to a 2018 world malaria report published by the World Health Organization (WHO).

Extensive efforts initiated in 2000 by malaria-affected countries and global health agencies have led to remarkable progress in reducing malaria-related deaths from more than one million to less than 500,000 per year. However, progress has been stagnant since 2015, and malaria is even re-emerging in some countries.

“Southern Research is looking forward to making important new contributions to malaria drug discovery with the extensive experience of Dr. Tekwani in this area and funding from the NIH-NIAID and the U.S. Department of Defense,” said Mark Suto, Ph.D., vice president of Drug Discovery at Southern Research.

The Department of Infectious Diseases in Southern Research’s Drug Discovery division focuses on a diverse array of infectious disease pathogens, with the objective of identifying novel mechanisms, targets and strategies for the prevention and treatment of protozoal, bacterial and viral infectious diseases throughout the world.

Tekwani has spent more than 30 years researching tropical parasitic diseases such as malaria, leishmaniasis and human African trypanosomiasis, vector-borne infectious diseases and major global health threats. His work on new drug discovery for infectious diseases has identified potential new targets and sources for therapies.

Southern Research teams with UAB to launch 3 pilot studies

Posted on February 20, 2019

How certain bacteria may make people more prone to asthma is one topic of three research grants jointly funded by Southern Research and the UAB School of Medicine.

These new research pilots are the latest effort to harness synergies between researchers at the University of Alabama at Birmingham and Southern Research, a Birmingham-based nonprofit research institute with nearly 400 scientists and engineers.

The two other pilots seek an improved way to develop new vaccines and a new mouse model for a potentially dangerous, hereditary deficiency shared by 400 million people worldwide.

The cooperation began with a July 2018 research retreat, sponsored by Art Tipton, Ph.D., president and chief executive officer of Southern Research, and Etty “Tika” Benveniste, Ph.D., senior vice dean for Basic Sciences in the UAB School of Medicine.

“While our researchers work together in many areas, we strongly suspected there would be additional ones that would be possible if both sides knew the research capabilities of each side better,” Tipton said. “And we were correct.”

“We announced at the end of it that we would fund some joint pilot programs,” Benveniste said. “Proposals were submitted and reviewed, and now three programs have been funded.”

This program parallels one held for the UAB School of Engineering, the College of Arts and Sciences, and Southern Research that was announced last July. That symposium was so successful it was repeated this month, and it will have additional funded programs to be announced later this year.

The one-year, $25,000 pilots were selected for intellectual merit, originality, potential to win major research funding and ability to foster collaborations between Southern Research and UAB.

Here are brief descriptions of the three pilots.

Javier Campos-Gómez of Southern Research and Beatriz León of UAB (Image: UAB)

ASTHMA STUDY

This study is based on the observation that human lung infections with the bacterium Pseudomonas aeruginosa are associated with more severe chronic cases of asthma and allergic sinusitis.

This suggests that the bacteria make people more susceptible to allergic airway inflammation, and that treating the lung infection could prevent severe asthma attacks. However, P.aeruginosa is often resistant to antibiotics.

The study is led by Southern Research principal investigator Javier Campos-Gómez, Ph.D., research associate biologist in the Department of Infectious Diseases, Drug Discovery Division, and UAB principal investigator Beatriz León, Ph.D., assistant professor in the Department of Microbiology

Campos-Gómez and León will investigate a different way to stymie P.aeruginosa, by probing the molecular basis for increased susceptibility to allergic inflammation and asthma in infected patients. They have preliminary evidence that a certain metabolite of P.aeruginosa may affect the immune response to allergens, and this could offer a new path to treatment therapies.

VACCINE DEVELOPMENT

Braden McFarland of UAB and Raj Kalkeri of Southern Research (Image: UAB)

This study starts with the understanding that the bacteria found in the human gastrointestinal track are necessary for the development of our immune system. However, 85 percent of bacteria found in the guts of laboratory mice are not found in the guts of humans, implying that vaccine efficacy evaluation with regular laboratory mice might not translate to humans.

The study is led by Southern Research principal investigator Raj Kalkeri, Ph.D., MBA, subject matter expert for infectious disease research in the Drug Development division, and UAB principal investigator Braden McFarland, Ph.D., instructor in the Department of Cell, Developmental and Integrative Biology.

Kalkeri and McFarland hope to bridge the knowledge gap through vaccine evaluation in humanized microbiome mice — mice that have human donor bacteria in their gastrointestinal tracts. This might be a better model to test potential human vaccine efficacy, as well as help reveal how gut microbes affect vaccine protection.

SAFETY OF THERAPEUTIC DRUGS

Babu L. Tekwani of Southern Research and Robert P. Kimberly of UAB (Image: UAB)

This study involves the hereditary condition called glucose 6-phosphate dehydrogenase, or G6PD, enzyme deficiency that affects more than 400 million people worldwide.

This enzyme deficiency can make people susceptible to drug-induced hemolytic anemia, and it can also limit use of several important drugs in public health. Yet development of safer drugs for these 400 million people has been hampered by lack of suitable experimental models for the enzyme deficiency.

The study is led by Southern Research principal investigator Babu L. Tekwani Ph.D., distinguished fellow and chair of infectious diseases in the Drug Discovery division, and UAB researchers in the Center for Clinical and Translational Science, Jennifer A. Croker, Ph.D., director of Administration, and Robert P. Kimberly, M.D., director.

Tekwani and colleagues will establish a model for the enzyme deficiency in humanized-immunocompromised mice, and then investigate the mechanism of drug-induced hemolytic anemia. This mouse model also should be useful to develop safer drug alternatives. Tekwani and his group are working on improving the safety of antimalarial drugs in populations with G6PD deficiency.