New $9.5M grant to launch innovative, interdisciplinary sickle cell disease research at the U of M

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Thursday, January 30, 2014

A new $9.5 million dollar grant awarded to researchers at the University of Minnesota is poised to launch an innovative effort designed to tackle pain associated with sickle cell disease. The grant is provided by the National Heart, Lung and Blood Institute within the National Institutes of Health.

The five-year, multi-disciplinary project will be led by Kalpna Gupta, Ph.D., co-leader of the Tumor Microenvironment Program in the Masonic Cancer Center and co-leader of the Molecular and Cellular Engineering Program in the Institute for Engineering in Medicine, University of Minnesota. Gupta is also an associate professor in the Division of Hematology, Oncology and Transplantation within the University’s Department of Medicine. Co-principal investigators are Bin He, Ph.D., Robert P. Hebbel, M.D., and Donald A. Simone, Ph.D., from the University of Minnesota, and Donald Abrams, M.D., of the University of California, San Francisco.

“Pain associated with sickle cell disease is disabling and can be life-long, but it takes a long time to develop new drugs, so we want to find novel ways to use currently available medications to treat these patients more effectively right now,” said Gupta.

Watch Gupta explain the project

For both researchers and patient advocacy groups, this latest grant is an important recognition of the importance of sickle cell disease, an inherited lifelong disease. Sickle cell disease is characterized by red blood cells morphing into an abnormal shape, leading to a variety of complications such as stroke and renal failure, as well as chronic pain and ulcers.

Currently treatment options for severe pain in sickle cell patients are limited to opioids. These medications are moderately effective but often pose the threat of addiction or increased tolerance.

The multidisciplinary project takes a multi-pronged approach to improve the understanding of pain and its treatment in this population. The new effort aims to:

  • Identify the mechanisms of pain in sickle cell disease, and investigate whether these mechanisms can be blocked using medications that are currently available or in advanced stages of development;
  • Develop technology to objectively quantify pain, for more personalized pain treatment;
  • Perform a clinical trial to test the effect of cannabinoids on pain in sickle cell patients;
  • Train young and future scientists dedicated to research and treatment of sickle cell disease.

Understanding the mechanisms of pain

“One of the most critical questions about pain in sickle cell patients is how that pain is being sparked,” said Gupta. “Ideally, we will find a way to block the molecular mechanisms that initiate and sustain pain.”

Finding the mechanisms of pain will allow for more effective and efficient treatment methods to evolve. Because the pain associated with sickle cell disease is so long lasting, it is important to address the pain from two angles: why the pain is so long-lasting and how pain can be quantified objectively.

Research is already underway to understand sensory neurons and responses to pain, utilizing a mouse model. This work is being led by Donald Simone, Ph.D., professor in the School of Dentistry and division director in the Division of Basic Sciences. He and his team have already found that mice with sickle cell disease have pain neurons in the spinal cord that respond abnormally to stimuli such as pressure.

“The next step will be to investigate how this sensitization occurs,” said Simone. “And then we can determine how to block it.”

Bin He, Ph.D., director of the Institute for Engineering in Medicine at the University of Minnesota and professor of biomedical engineering, has been working on quantitative electroencephalography (EEG) technology for many years, searching for a way to offer an objective and quantitative assessment of pain. The He lab uses this technology to derive biomarkers associated with pain and to record the brain waves produced by networks involved in pain generation and processing. 

“This grant provides an opportunity to study pain in sickle cell disease, which is a new application for our technology,” said He. “This type of noninvasive pain assessment may positively impact patient care by giving an objective assessment for physicians to utilize in making care decisions.”

Clinical trial

Gupta and her research partners believe cannabinoids may be the best currently available alternative to opioids for treatment of pain in patients with sickle cell disease.

“Opioids open up a lot of problems, including building tolerance and creating potential addiction issues. We want to find better ways to treat pain in these patients outside the current standard of opioids,” said Gupta.

She turned to collaborator Donald Abrams, M.D., director of the Osher Center for Integrative Medicine and a professor of clinical medicine at the University of California, San Francisco (UCSF) and an expert in utilizing cannabis for clinical care. Together, they designed a trial at UCSF to test the effectiveness of vaporized cannabis in treating the pain associated with sickle cell disease.

This trial is beginning soon at UCSF, under the guidance of Abrams.

Training

“The training component of this grant is one I’m very excited about,” said Gupta. “It helps us create a group of researchers and care providers who will focus on this issue for many years to come.”

A portion of the grant will support young researchers of all levels as they begin their efforts investigating sickle cell disease. The project will support contributors as young as high school students, to help develop their interest in battling this disease and bettering the lives of patients.

Funding for this project comes from the National Institutes of Health 1UO1HL117664-01.