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Researchers at St. Jude Children’s Research Hospital tirelessly and brilliantly work to advance cures for, and prevent, pediatric catastrophic diseases through research and treatment; and in their work they make discoveries beyond our core mission. These discoveries require further development, so our office endeavors to license them to companies who will turn them into successful products. Here are just a few examples of discoveries licensed from St. Jude that have been incorporated into products or processes that are now deployed in the marketplace.
For over 100 years, antibiotics have been used to fight bacterial infection and disease. However, bacteria are increasingly developing resistance to front line antibiotics, and new therapies are needed to treat these bacterial strains. Dr. Richard Lee, Ph.D., a member of the St. Jude Department of Chemical Biology and Therapeutics, is developing two new classes of compounds to be effective in treating strains that are no longer effectively treated with current therapies. One compound is an adaptation of an old antibiotic- Spectinomycin, which is modified using structure based drug design. The other compound is designed to treat chronic infections and biofilms caused by persister cells that have become tolerant of existing antibiotics. Both compound classes are described below:
Treating resistant bacteria
Dr. Lee’s laboratory designed a promising new class of antibiotics, called aminomethyl spectinomycins, which follows his work on Spectinomycin analogs for treating tuberculosis. In this case a new series of spectinomycin analogs has been developed for treating a broad spectrum of respiratory tract infections including S. pnuemoniae, the most common pathogenic bacteria associated with this type of infection. The aminomethyl spectinomycins are active against drug resistant strains. In collaboration with Dr. Jason Rosch in the Infectious Diseases department, the robust efficacy of this compound series has been demonstrated at low compound dosing levels, further validating this series. These compounds have been licensed by Microbiotix, a privately-held, clinical stage biopharmaceutical company engaged in the discovery and development of novel small molecule anti-infectives. “This study demonstrates how classic antibiotics derived from natural products can be redesigned to create semi-synthetic compounds to overcome drug resistance.” stated Dr. Lee.
Treating tolerant bacteria
Dr. Lee and his collaborators developed another set of compounds designed to treat bacteria, fungi and parasites that develop multidrug tolerance by becoming dormant. Small subpopulations of tolerant microbial cells are called persister cells, because they can survive the antimicrobial treatments that kill their genetically identical siblings. When persister cells are left behind, they become a reservoir from which an infection can recur. Examples of chronic infections include endocarditis, urinary tract infections, gingivitis, middle ear infections, fatal lung disease (cystic fibrosis) and infections produced by biofilms. These infections are often associated with implanted medical devices, such as catheters and artificial joints. Multidrug tolerant infections account for more than 60% of all microbial infections, are hard to treat and subject to infection relapse. Traditional antibiotics kill active cells via inhibition; however, this new set of compounds acts to kill dormant cells. They could be used to treat infections caused by biofilms; and other infections caused by chronic bacteria persister cells. These compounds have been licensed to Arietis, a Boston-based biotechnology company, focused on the discovery and development of novel antimicrobial agents.
St. Jude Children’s Research Hospital is known for performing groundbreaking and life changing research; and the Office of Technology Licensing endeavors to facilitate the development of innovations originating during this research into products that can benefit St. Jude patients and the public at large. Sometimes, small things can make a big difference, as is the case with Flowmi™ Cell Strainers, a filter co-designed by Dr. Steven Zatechka at St. Jude and researchers Bel-Art Labs to improve flow cytometry. Flowmi is a fast and efficient cell strainer that joins to the end a micropipette tip and allows users to strain debris from a sample just prior to analysis by flow cytometers. These filters are designed to preserve sample volume and avoid clogs, and are recommended for use with samples having a maximum concentration of 2MM cells/ml. Find out more about Flowmi on their website: http://www.belart.com/flowmi/
St. Jude Children’s Research Hospital is internationally recognized for its pioneering research and treatment of children with cancer; however, research of a far more common yet deadly disease also thrives here. For many years, St. Jude has been a global leader in the study of influenza because cancer patients undergoing treatments that diminish the immune system are at much more serious risk of death from infectious diseases like influenza; however, the impact of this disease extends far beyond the walls of St. Jude.
KIR/KIR-Ligand Assay predicts the success of bone marrow transplants and prevents the return of cancer in transplant recipients. As part of the licensing agreement, Insight Genetics will optimize the test for rapid, high-capacity use and make it broadly available to physicians and their patients as well as donor registries (SJ-10-0024).
PRO-PredictRx TPMT® is a genetic assay doctors can use to help determine the correct dosage of thiopurines for their patients. The Prometheus Laboratories assay uses a discovery by Drs. William Evans and Eugene Krynetski of three mutations in the thiopurine S-methyltransferase (TPMT) gene that leave patients with a decreased ability to metabolize standard doses of thiopurines such as the leukemia drug 6-mercaptopurine. Patients with decreased ability to metabolize thiopurines can be identified by this assay and receive substantially the same benefit from reduced dosages of these drugs while avoiding toxic side effects.
FastImmune Cytokine System® was developed by BD Biosciences to rapidly analyze human lymphocyte activation and detect intracellular cytokines by flow cytometry. It contains an anti-CD19 monoclonal antibody (SJ25C1) developed at St. Jude. Determining intracellular cytokine levels in response to antigen activation can be used in the study of autoimmune diseases, HIV, tumor vaccine development, allergies and infectious diseases.
Oncomark 3-Color Oncomark Combinations® is an antibody cocktail from BD Biosciences used to study leukemia. In addition to the anti-CD19 monoclonal antibody (SJ25C1) developed at St. Jude which recognizes CD19 expressed on human B lymphocytes at most stages of maturation, this cocktail contains anti-CD79b, which is expressed at high levels in most B-cell disorders and either anti-kappa or anti-lamba which is present on neoplastic cells.
The ALK gene was discovered (SJ-93-0002) in the 1990s by St. Jude scientists searching for genes affected by a chromosomal change common in the cancer cells of pediatric patients with anaplastic large cell lymphoma (ALCL). This discovery led to issued patents that were licensed to develop therapeutics for treatment of adult lung cancers. So far two ALK inhibitor drugs have been approved by the US Food and Drug Administration (FDA). Over 200,000 new cases of lung cancer are diagnosed in the U.S. each year. Current estimates are approximately 3-5% (6,500 to 11,000) patients with non-small cell lung cancer carry the ALK rearrangement and may be candidates for treatment with the drugs:
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