According to the May 10, 2013 news item on Nanowerk,
DARPA, the U.S. Defense Advanced Research Projects Agency, has awarded $6 million to a team of researchers to develop nanotechnology therapies for the treatment of traumatic brain injury and associated infections.
Led by Professor Michael J. Sailor, Ph.D., from the University of California San Diego [UC San Diego], the award brings together a multi-disciplinary team of renowned experts in laboratory research, translational investigation and clinical medicine, including Erkki Ruoslahti, M.D., Ph.D. of Sanford-Burnham Medical Research Institute, Sangeeta N. Bhatia, M.D., Ph.D. of Massachusetts Institute of Technology and Clark C. Chen, M.D., Ph.D. of UC San Diego School of Medicine.
Ballistics injuries that penetrate the skull have amounted to 18 percent of battlefield wounds sustained by men and women who served in the campaigns in Iraq and Afghanistan, according to the most recent estimate from the Joint Theater Trauma Registry, a compilation of data collected during Operation Iraqi Freedom and Operation Enduring Freedom.
“A major contributor to the mortality associated with a penetrating brain injury is the elevated risk of intracranial infection,” said Chen, a neurosurgeon with UC San Diego Health System, noting that projectiles drive contaminated foreign materials into neural tissue.
The May 9, 2013 UC San Diego news release by Susan Brown, which originated the news item, describes the reasons why DARPA wants to use nanoparticles in therapies for people suffering from traumatic brain injury,
Under normal conditions, the brain is protected from infection by a physiological system called the blood-brain barrier. “Unfortunately, those same natural defense mechanisms make it difficult to get antibiotics to the brain once an infection has taken hold,” said Chen, associate professor and vice-chair of research in the Division of Neurosurgery at UC San Diego School of Medicine.
DARPA hopes to meet these challenges with nanotechnology. The agency awarded this grant under its In Vivo Nanoplatforms for Therapeutics program to construct nanoparticles that can find and treat infections and other damage associated with traumatic brain injuries.
“Our approach is focused on porous nanoparticles that contain highly effective therapeutics on the inside and targeting molecules on the outside,” said Sailor, the UC San Diego materials chemist who leads the team. “When injected into the blood stream, we have found that these silicon-based particles can target certain tissues very effectively.”
Several types of nanoparticles have already been approved for clinical use in patients, but none for treatment of trauma or diseases in the brain. This is due in part to the inability of nanoparticle formulations to cross the blood-brain barrier and reach their intended targets.
“Poor penetration into tissues limits the application of nanoparticles to the treatment of many types of diseases,” said Ruoslahti, distinguished professor at Sanford-Burnham and partner in the research. “We are trying to overcome this limitation using targeting molecules that activate tissue-specific transport pathways to deliver nanoparticles.”
There is another major hurdle for treating brain injuries (from the news release),
Treating brain infections is becoming more difficult as drug-resistant strains of viruses and bacteria have emerged. Because drug-resistant strains mutate and evolve rapidly, researchers must constantly adjust their approach to treatment.
In an attempt to hit this moving target, the team is making their systems modular, so they can be reconfigured “on-the-fly” with the latest therapeutic advances.
Nanocomplexes that contain genetic material known as short interfering RNA, or siRNA, developed by Bhatia’s research group at MIT, will be key to this aspect of the team’s approach.
“The function of this type of RNA is that it specifically intereferes with processes in a diseased cell. The advantage of RNA therapies are that they can be quickly and easily modified when a new disease target emerges,” said Bhatia, a bioengineering professor at MIT and partner in the research.
But effective delivery of siRNA-based therapeutics in the body has proven to be a challenge because the negative charge and chemical structure of naked siRNA makes it very unstable in the body and it has difficulty crossing into diseased cells. To solve these problems, Bhatia has developed nanoparticles that form a protective coating around siRNA.
“The nanocomplexes we are developing shield the negative charge of RNA and protect it from nucleases that would normally destroy it. Adding Erkki’s tissue homing and cell-penetrating peptides allows the nanocomplex to transport deep into tissue and enter the diseased cells,” she said.
Bhatia has previously used the cell-penetrating nanocomplex to deliver siRNA to a tumor cell and shut down its protein production machinery. Although her group’s effort has focused on cancer, the team is now going after two other hard-to-treat cell types: drug-resistant bacteria and inflammatory cells in the brain.
“The work proposed by this multi-disciplinary team should provide new tools to mitigate the debilitating effects of penetrating brain injuries and offer our warfighters the best chance of meaningful recovery,” Chen said. [emphasis mine]
BTW, the term ‘warfighters’ is new to me; are we replacing the word ‘soldier’?
Returning to the matter at hand, I found DARPA’s In Vivo Nanoplatforms for Therapeutics program which is described this way on its home page,
Disease limits soldier readiness and creates healthcare costs and logistics burdens. Diagnosing and treating disease faster can help limit its impact. [emphasis mine] Current technologies and products for diagnosing disease are principally relegated to in vitro (in the lab) medical devices, which are often expensive, bulky and fragile.
DARPA’s In Vivo Nanoplatforms (IVN) program seeks to develop new classes of adaptable nanoparticles for persistent, distributed, unobtrusive physiologic and environmental sensing as well as the treatment of physiologic abnormalities, illness and infectious disease.
The IVN Diagnostics (IVN:Dx) program effort aims to develop a generalized in vivo platform that provides continuous physiological monitoring for the warfighter. [emphasis mine] Specifically, IVN:Dx will investigate technologies that may provide:
- Implantable nanoplatforms using bio-compatible and nontoxic materials
- In vivo sensing of small and large molecules of biological interest
- Multiplexed detection of analytes at clinically relevant concentrations
- External interrogation of the nanoplatform free from any implanted communications electronics
- Complete system demonstration in a large animal
The IVN Therapeutics (IVN:Tx) program effort will seek unobtrusive nanoplatforms for rapidly treating disease in warfighters.
(I see DARPA is using both soldier and warfighter’.)
This team is not the only one wishing to deliver drug therapies in a targeted fashion to the brain. My Feb. 19, 2013 posting mentioned Chad Mirkin (Northwestern University) and his team’s efforts with spherical nucleic acids (SNAs), from the posting,
Potential applications include using SNAs to carry nucleic acid-based therapeutics to the brain for the treatment of glioblastoma, the most aggressive form of brain cancer, as well as other neurological disorders such as Alzheimer’s and Parkinson’s diseases. Mirkin is aggressively pursuing treatments for such diseases with Alexander H. Stegh, an assistant professor of neurology at Northwestern’s Feinberg School of Medicine. (originally excerpted from this the Feb. 15, 2013 news release on EurekAlert)
Coincidentally, Mirkin has just been named ‘Chemistry World Entrepreneur of the Year’ by the UK’s Royal Society of Chemistry, from the May 10, 2013 news item on Nanowerk,
Northwestern University scientist Chad A. Mirkin, a world-renowned leader in nanotechnology research and its application, has been named 2013 Chemistry World Entrepreneur of the Year by the Royal Society of Chemistry (RSC). The award recognizes an individual’s contribution to the commercialization of research.
The RSC is honoring Mirkin for his invention of spherical nucleic acids (SNAs), new globular forms of DNA and RNA. These structures form the basis for more than 300 products commercialized by licensees of the technology.
I’m never quite sure what to make of researchers who receive public funding then patent and license the results of that research.
Getting back to soldiers/warfighters, I’m glad to see this research being pursued. Years ago, a physician mentioned to me that soldiers in Iraq were surviving injuries that would have killed them in previous conflicts. The problem is that the same protective gear which insulates soldiers against many injuries makes them vulnerable to abusive head trauma (same principle as ‘shaken baby syndrome’). For example, imagine having a high velocity bullet hit your helmet. You’re protected from the bullet but the impact shakes your head so violently, your brain is injured.