The U.S. Food and Drug Administration today announced that it has awarded 21 new clinical trial research grants totaling more than $23 million over the next four years to boost the development of products for patients with rare diseases. These new grants were awarded to principal investigators from academia and industry with research spanning domestic and international clinical sites.
“We are proud of our 30-year track record of fostering and encouraging the development of safe and effective therapies for rare diseases through our clinical trials grant program,” said Gayatri R. Rao, M.D., J.D., director of FDA’s Office of Orphan Product Development, within the Office of Special Medical Programs. “The grants awarded this year will support much-needed research in 21 different rare diseases, many of which have little, or no, available treatment options.”
The FDA awards the grants through the Orphan Products Clinical Trials Grants Program to encourage clinical development of drugs, biologics, medical devices, or medical foods for use in rare diseases. The grants are intended for clinical studies evaluating the safety and effectiveness of products that could either result in, or substantially contribute to, the FDA approval of products.
Since its creation in 1983, the Orphan Products Clinical Trials Grants Program has provided more than $370 million to fund more than 590 new clinical studies and supported the marketing approval of more than 55 products. Five of the studies funded by this grants program supported product approvals in 2015 alone, including much needed treatments for neuroblastoma, lymphangioleiomyomatosis, hypoparathyroidism, and hypophosphatasia.
Consistent with the tenor set by Vice President Joe Biden’s National Cancer Moonshot Initiative to accelerate cancer research, 24 percent of the new grant awards fund studies enrolling patients with cancer; 40 percent of these studies target devastating forms of brain cancer, one of which recruits children with recurrent or progressive malignant brain tumors.
Forty-three percent of this year’s awards fund studies that enroll pediatric patients as young as newborns. Of these, two focus on research in transplantation and related issues.
In addition, one funded project is a medical device trial to develop a fully implantable neuroprosthesis for grasp, reach, and trunk function in individuals with spinal cord injury with the potential to enable these patients to use their hand, arm, and trunk more independently.
A total of 68 grant applications were received for this fiscal year, with a funding rate of 31 percent (21/68). The grant recipients for fiscal year 2016 include:
- Chemigen, LLC (Zionsville, Indiana), Yansheng Du, Phase 1 Study of CC100 for the Treatment of Amyotrophic Lateral Sclerosis — about $243,000 for one year
- Chemocentryx, Inc. (Mountain View, California), Petrus Bekker, Phase 2 Study of CCX168 for the Treatment of Anti-Neutrophil Cytoplasmic Auto-Antibodies Associated Vasculitis — $500,000 for one year
- Columbia University Health Sciences (New York, New York), Elizabeth Shane, Phase 2B Study of Denosumab to Prevent Bone Loss in Idiopathic Osteoporosis in Premenopausal Women Treated with Terripatide — about $1.6 million over four years
- DNATRIX, Inc. (Houston, Texas), Frank Tufaro, Phase 2 Study of DNX-2401 for the Treatment of Glioblastoma — $2 million over four years
- Elorac, Inc. (Vernon Hills, Illinois), Scott Phillips, Phase 3 Study of Naloxone Lotion for the Treatment of Pruritus in Mycosis Fungoides — about $2 million over four years
- Johns Hopkins University (Baltimore, Maryland), Pamela Zeitlin, Phase 1/2 Study of Glycerol Phenylbutyrate for the Treatment of Cystic Fibrosis — $750,000 over three years
- Oncoceutics, Inc. (Hummelstown, Pennsylvania), Wolfgang Oster, Phase 1/2 Study of ONC201 for the Treatment of Multiple Myeloma — about $1.7 million over four years
- Oregon Health and Science University (Portland, Oregon), Kevin Winthrop, Phase 2 Study of Clofazimine for the Treatment of Pulmonary Mycobacterium Avium Disease — about $1.8 million over four years
- Santhera Pharmaceuticals (Liestal, Switzerland), Thomas Meier, Phase 1 Study of Omigapil for the Treatment of Congenital Muscular Dystrophy — $246,000 for one year
- Scioderm, Inc. (Durham, North Carolina), Jay Barth, Phase 3 Study of SD101 for the Treatment of Epidermolysis Bullosa — $500,000 for one year
- Seattle Children’s Research Institute (Seattle, Washington), Leslie Kean, Phase 2 Study of Abatacept Combined with Calcineurin Inhibition and Methotrexate for Prophylaxis of Graft Vs Host Disease — $99,630 for one year
- Sloan-Kettering Institute Cancer Research (New York, New York), Katharine Hsu, Phase 1 Study of Humanized 3F8 MoAb and NK cells for the Treatment of Neuroblastoma — about $750,000 over three years
- Taimed Biologics USA Corp (Irvine, California), Stanley Lewis, Phase 3 Study of Ibalizumab for the Treatment of Patients with Multidrug Resistant HIV — $500,000 for one year
- University of Alabama (Birmingham, Alabama), Gregory Friedman, Phase 1 Study of HSV G207 & Radiation for the Treatment of Pediatric Brain Tumors — about $750,000 over three years
- University of California, San Diego (La Jolla, California), Donald Durden, Phase 1 Study of PI-3 Kinase/BRD4 Inhibitor SF1126 for the Treatment of Hepatocellular Carcinoma — $750,000 over three years
- University of Florida (Gainesville, Florida), Peter Stacpoole, Phase 3 Study of Dichloroacetate for the Treatment of Pyruvate Dehyrugenase Complex Deficiency — about $2 million over four years
- University of Michigan (Ann Arbor, Michigan), Kathleen Stringer, Phase 2 Study of Inhaled Activase for the Treatment of Acute Plastic Bronchitis — $2 million over four years
- University of North Carolina Chapel Hill (Chapel Hill, North Carolina), Matthew Laughon, Phase 2 Study of Furosemide for the Prevention of Bronchopulmonary Dysplasia in Premature Infants — about $1.4 million over four years
- Vanderbilt University Medical Center (Nashville, Tennessee), Cyndya Shibao, Phase 2 Study of Atomoxetine for the Treatment of Multiple System Atrophy — about $1.6 million over four years
- Wilson Wolf Manufacturing Corporation (New Brighton, Minnesota), Sunitha Kakarla, Phase 1 Study of Viralym-A for the Treatment of Adenovirus Disease — about $750,000 over three years
- Case Western Reserve University (Cleveland, Ohio), Kevin Kilgore, Phase 2 Study of a Networked Neuroprosthesis for Grasp, Reach, and Trunk Function in Cervical Spinal Cord Injury — about $2 million over four years
The brain may not only control our thoughts and basic physical functions.
Recent studies indicate that it also controls the way our body responds to the threat of bacterial infections. It does this by boosting the production of a protective molecule called PCTR1 that helps white blood cells kill the invading bacteria.
Our body is in constant contact with bacteria. For the most part these do not pose a threat since we have evolved defence systems to keep these organisms at bay.
But in some instances, especially when the body’s defence systems are weakened or fail, bacteria may invade, leading to infection and, in extreme cases, sepsis, which can result in death.
In the 1920s, a breakthrough discovery was made: the identification of the antibiotic properties of penicillin. The discovery paved the way to a new era in infection treatment.
With antibiotics, we no longer had to rely on our body to get rid of bacteria. Instead, we could give it a helping hand by stunting the ability of bacteria to replicate, thus giving our immune system enough time to clear them.
Penicillin was the first in a long list of antibiotics developed to tackle different types of bacterial infections.
However, over the last few decades, the ability of antibiotics to stop bacterial growth has become considerably limited and increasing numbers of bacterial strains are becoming resistant to antibiotic treatment.
The threat of antibiotics resistance has prompted the scientific community to seek alternative ways to deal with bacterial infections.
A very important molecule
To identify novel avenues to treat bacterial infections we turned our focus to the central nervous system (the brain, spinal cord and optic nerves), as several studies have implicated the brain in orchestrating more than just our thoughts.
In our study we found that severing the right vagus nerve in mice, for example, leads to a significant impairment in their ability to clear E. coli infections.
When we investigated the reason for this delay, we found a significant decrease in the levels of a molecule called “protectin conjugate in tissue regeneration 1”, or PCTR1 for short.
PCTR1 is part of a group of molecules called specialised pro-resolving mediators that control how our body responds to inflammation. It is produced by white blood cells from a fish oil-derived essential fatty acid called docosahexaenoic acid.
We also found that the decrease in PCTR1 reduced the ability of macrophages – a type of white blood cell – to kill E. coli.
We then investigated how the vagus nerve regulates PCTR1 production in the abdominal cavity of the mice, where this nerve is known to regulate white blood cell behaviour during inflammation.
Here we found that the nerve releases a neurotransmitter called acetylcholine which then instructs another type of immune cell (innate lymphoid cells) to increase production of PCTR1. This in turn regulated macrophages’ ability to find and kill bacteria.
When we injected the mice with the severed vagus nerve with PCTR1, we found that it restored the ability of peritoneal macrophages to get rid of the bacteria as well as dampen the subsequent inflammatory response, accelerating the bacteria’s termination.
These results are expected to have wide-ranging implications in the fight against bacterial infections, especially in light of the alarming rate at which bacteria are becoming resistant to antibiotics.
This is because these findings demonstrate that we can give our body a hand by using PCTR1, and related molecules, to enhance its ability to clear bacteria during infections, reducing our reliance on antibiotics.