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BuzzKill:
                                              How Malaria
                                              Has, and Is,
                                              Changing the
                                              World We
Brian T. Grimberg, Ph.D.
Assistant Professor of International Health   Live In
Center for Global Health and Diseases
An NIH International Center for Excellence
for Malaria Research




                                              TEDxCLE April 20th, 2012
                                                   B. Grimberg, 2012 ©
3,500,000,000


  EXPOSED
       Courtesy of the Malaria Atlas Project
1,200,000


 DEATHS
     Courtesy of the Malaria Atlas Project
Why Are We Here?


  Public
  Square




Cleveland, 1877
                   maps.com
Malaria is Transmitted by Female
    Anopheline Mosquitoes
After 2 weeks of Digestion the
 Mosquito Finds a New Host
Eliminating Malaria Will Be More
Significant Than the Moon Landing
   • Eliminating malaria will cost
     more, take longer, and be more
     challenging than landing on the
     moon
   • It will have a greater global
     impact
In Science, the Key to Solving
     Big Problems is Team Work
• Solving malaria requires multidisciplinary
  teams focused on
   – Prevention
   – Detection
   – Treatment
• Teams include
  – Biologists, Chemists, Engineers, Physicists, Medical
    Personnel, NGOs, and Funding
Center
   for
 Global
Health &
Diseases
International
  Center of
Excellence for
   Malaria
  Research
Prevention: The Problem




                          National Geographic
                          2007
Prevention: Idea and A Solution
• Project: Wide Distribution of Bednets
• Team: CWRU Center for Global Health & Diseases,
  UNF, NBN
Prevention: Another Idea
• Project:
  – Develop, perform, and test virtual (in silico)
    screening for malaria vaccine candidates
• Team:
  –   CWRU Center for Global Health & Diseases
  –   CWRU Department of Biochemistry
  –   CWRU HPCC
  –   NIH (AI079388)
Prevention:
    Solution
• Search millions of
  compounds rapidly
  to identify potential
  malaria vaccines
  using computers
Detection: The Problem
• Malaria detection by slide and microscopy is
  lengthy and subjective
Field Site Conditions can
 Compromise Detection
Detection: Idea
• Project:
  – Exploit physical properties of malaria to
    develop cost-effective, field-ready device
    for rapid detection
• Team:
  –   CWRU Center for Global Health & Diseases
  –   CWRU Physics
  –   CWRU Biomedical Engineering
  –   Wallace H. Coulter Foundation
  –   Clinical Translational Science Collaborative
      (UL1RR024989)
Malaria Parasites Digest
Hemoglobin of Erythrocytes
Detection: A Solution
                                   Sample
                       Polarizer

                                                Detector
Laser




 View of        Hemozoin
Hemozoin


           Randomly Oriented
               Hemozoin
                                       Magnet
Detection: A Solution
                                   Sample
                       Polarizer

                                                   Detector
Laser




 View of         Hemozoin                Magnet (0.5 Tesla)
Hemozoin


           Aligned Hemozoin Reduces Amount of Polarized
                      Light Through a Sample
Treatment: The Problem
• Malaria parasites show resistance to all classes
  of existing drugs
      Getty Images




                                  thelancet.com/malaria-elimination
Treatment: The Problem(s)
• Patients need to return to clinics when
  medications fail (up to a 3 day walk)
Treatment: Idea
• Project:
  – Screen drugs FDA-approved for other indications for anti-
    malarial activity
  – Screen natural treatments for anti-malarial activity
• Team:
  –   CWRU Center for Global Health & Diseases
  –   Curragh Chemistries (Cleveland, OH)
  –   University of Utah
  –   Medicines for Malaria Venture
  –   CWRU School of Medicine
      Vision Fund
Treatment: A Solution
SU 11274 2
• Originally developed as a drug for leukemia
• Acts as an ATP competitive inhibitor of the catalytic activity of MET
               3F C
                             H
                             N
                                    H
                                    N
                                                       N
  (similar to Gleevec®)
• In vitro and In vivo studies confirm anti-malarial activity
                 Cl             O
                                              O
• Provisional patent filed        1

                   Cl                                     O
                                                                 N
                                                                 H
                                                     O



                                                                  N
                          NH

                        O 2S                N
                                            H
                                        O

                                    N
                                    H

                                2


                               CN               CN
                                                         BT Grimberg, et al, 2009
Treatment: A Solution


                                 Fascaplysinopsis reticulata




Bromohomofascaplysin A   Homofascaplysin A           Fascaplysin


                                                          Lu, et al. 2011
Malaria is a
 Disease of
  Poverty

• Prevention

• Detection

• Treatment
While I’ve been talking…
 17,123
  PEOPLE WERE
    INFECTED
34


CHILDREN DIED
You Can Be Part of Our Team!
         • Learn More About
           CWRU Center for Global
           Health & Diseases
           – case.edu/orgs/cghd
         • Write to Congress
           – President’s Malaria Initiative
           – Global Fund
         • Learn More about Bednets
           – Nothingbutnets.net
And help those affected by malaria
TEDxCLE - Brian Grimberg - Buzzkill: How Malaria Has, and Is, Changing The World We Live In

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TEDxCLE - Brian Grimberg - Buzzkill: How Malaria Has, and Is, Changing The World We Live In

  • 1. BuzzKill: How Malaria Has, and Is, Changing the World We Brian T. Grimberg, Ph.D. Assistant Professor of International Health Live In Center for Global Health and Diseases An NIH International Center for Excellence for Malaria Research TEDxCLE April 20th, 2012 B. Grimberg, 2012 ©
  • 2. 3,500,000,000 EXPOSED Courtesy of the Malaria Atlas Project
  • 3. 1,200,000 DEATHS Courtesy of the Malaria Atlas Project
  • 4. Why Are We Here? Public Square Cleveland, 1877 maps.com
  • 5. Malaria is Transmitted by Female Anopheline Mosquitoes
  • 6. After 2 weeks of Digestion the Mosquito Finds a New Host
  • 7.
  • 8. Eliminating Malaria Will Be More Significant Than the Moon Landing • Eliminating malaria will cost more, take longer, and be more challenging than landing on the moon • It will have a greater global impact
  • 9. In Science, the Key to Solving Big Problems is Team Work • Solving malaria requires multidisciplinary teams focused on – Prevention – Detection – Treatment • Teams include – Biologists, Chemists, Engineers, Physicists, Medical Personnel, NGOs, and Funding
  • 10. Center for Global Health & Diseases International Center of Excellence for Malaria Research
  • 11. Prevention: The Problem National Geographic 2007
  • 12. Prevention: Idea and A Solution • Project: Wide Distribution of Bednets • Team: CWRU Center for Global Health & Diseases, UNF, NBN
  • 13. Prevention: Another Idea • Project: – Develop, perform, and test virtual (in silico) screening for malaria vaccine candidates • Team: – CWRU Center for Global Health & Diseases – CWRU Department of Biochemistry – CWRU HPCC – NIH (AI079388)
  • 14. Prevention: Solution • Search millions of compounds rapidly to identify potential malaria vaccines using computers
  • 15. Detection: The Problem • Malaria detection by slide and microscopy is lengthy and subjective
  • 16. Field Site Conditions can Compromise Detection
  • 17. Detection: Idea • Project: – Exploit physical properties of malaria to develop cost-effective, field-ready device for rapid detection • Team: – CWRU Center for Global Health & Diseases – CWRU Physics – CWRU Biomedical Engineering – Wallace H. Coulter Foundation – Clinical Translational Science Collaborative (UL1RR024989)
  • 19. Detection: A Solution Sample Polarizer Detector Laser View of Hemozoin Hemozoin Randomly Oriented Hemozoin Magnet
  • 20. Detection: A Solution Sample Polarizer Detector Laser View of Hemozoin Magnet (0.5 Tesla) Hemozoin Aligned Hemozoin Reduces Amount of Polarized Light Through a Sample
  • 21. Treatment: The Problem • Malaria parasites show resistance to all classes of existing drugs Getty Images thelancet.com/malaria-elimination
  • 22. Treatment: The Problem(s) • Patients need to return to clinics when medications fail (up to a 3 day walk)
  • 23. Treatment: Idea • Project: – Screen drugs FDA-approved for other indications for anti- malarial activity – Screen natural treatments for anti-malarial activity • Team: – CWRU Center for Global Health & Diseases – Curragh Chemistries (Cleveland, OH) – University of Utah – Medicines for Malaria Venture – CWRU School of Medicine Vision Fund
  • 24. Treatment: A Solution SU 11274 2 • Originally developed as a drug for leukemia • Acts as an ATP competitive inhibitor of the catalytic activity of MET 3F C H N H N N (similar to Gleevec®) • In vitro and In vivo studies confirm anti-malarial activity Cl O O • Provisional patent filed 1 Cl O N H O N NH O 2S N H O N H 2 CN CN BT Grimberg, et al, 2009
  • 25. Treatment: A Solution Fascaplysinopsis reticulata Bromohomofascaplysin A Homofascaplysin A Fascaplysin Lu, et al. 2011
  • 26. Malaria is a Disease of Poverty • Prevention • Detection • Treatment
  • 27. While I’ve been talking… 17,123 PEOPLE WERE INFECTED
  • 29. You Can Be Part of Our Team! • Learn More About CWRU Center for Global Health & Diseases – case.edu/orgs/cghd • Write to Congress – President’s Malaria Initiative – Global Fund • Learn More about Bednets – Nothingbutnets.net
  • 30. And help those affected by malaria

Editor's Notes

  1. How many of you have been to a malaria region.Ask a question
  2. TALK ABOUT GLOBAL WARMINGwhelming majority of these under the age of 5Malaria is a disease of poverty 600,000,000.clinical casesExplain Heat map
  3. Mostly children500 Million estimated cases1.2 Million Report Deaths per yearMany more unreported deathsThe overwhelming majority of these under the age of 5
  4. 19th CenturyUniversity Circle was known during the early 19th Century as Doan’s Corners, after Nathanial Doan, a member of the Connecticut Land Company, who settled his family and started a community here.The name "University Circle" began to take shape in the 1880s. Western Reserve University moved its campus from Hudson, Ohio, to Euclid Avenue in 1883. Case School of Applied Science moved from Downtown Cleveland to a site next to WRU in 1885. Their relocation led to the birth of an educational center and the creation of a new community called University Circle, named in part after these new institutions - but also the circular street intersection and trolley turnaround located Euclid Avenue and Doan Brook Boulevard (Martin Luther King Jr Boulevard today).[20]By the 1890s, the Western Reserve School of Design for Women (Cleveland Institute of Art) moved to University Circle, and the concept of developing a world-class arts and cultural center came to life. The concept became more concrete when Jeptha Wade, a trustee of Western Reserve University, set aside land for the Cleveland Museum of Art to be built in the Circle. The Historical Society (Western Reserve Historical Society) joined these institutions before the turn of the 19th to 20th century. [21][edit] 20th CenturyThe Circle began to grow rapidly in the early 20th century. The Cleveland Museum of Art opened its doors in 1916. By the 1920s and 1930s, nineteen educational and cultural institutions were located in the area, from the Cleveland Museum of Natural History to the Cleveland Hearing and Speech Center to the Cleveland Botanical Garden and others.The arrival of University Hospitals in 1931 (founded in 1866) led to health care becoming another center of innovation in University Circle. Less than one mile away from University Hospitals, the Cleveland Clinic had been serving its patients since 1921. Also in 1931 Severance Hall, home of the Cleveland Orchestra, was constructed at the corner of Euclid and East Blvd.[21] By 1950, 34 institutions had chosen University Circle as their home.[20] In 1967, Case School of Applied Science and Western Reserve University confederated to become Case Western Reserve University.[22][edit] 21st CenturyThe history of University Hospitals Case Medical Center is linked to the history of Cleveland. Founded in 1866, we were nurtured and supported by Cleveland's great industrial families of the late 19th and early 20th centuries – the same families that played key roles in the development of the city's noted civic and cultural institutions, including the Cleveland Museum of Art,
  5. >1,000 bites per night, Moses 1996
  6. Maybe add the amount of funding 109 Billion
  7. Label buildings
  8. 2 minutes and the machine cost $200
  9. For leukemia and GI tumors
  10. Say out loud
  11. workforce sick all the time taking days off to take sick children to the clinics for treatmentworkforce sick all the time taking days off to take sick children to the clinics for treatmentworkforce sick all the time taking days off to take sick children to the clinics for treatmentAnd many other diseases too
  12. Say that you will be at congress next week