Good things come in small packages; at least that’s what the European Union (EU) is banking on. The EU’s current major funding initiative for research, the Seventh Framework Programme (FP7), is making a push for projects that apply nanotechnology to disease diagnosis and therapy. About $15 million went to one big collaborative project on Alzheimer’s disease (AD), and millions more to other joint projects, individual investigators, and training grants, according to a July 28 editorial in Nanomedicine by Cristina Gabellieri and Heico Frima of the EU’s directorate general for research and innovation. Nanotechnology in Alzheimer’s is a young field, with data starting to appear in the literature only in the past couple of years and more coming out this past summer.
Most research in the 27 EU member countries is funded at the national level by private and public sources, but the framework programs, which have been ongoing since 1984, provide additional cash for European researchers. The FP7, which started in 2007 and will continue until 2013 with a budget of €53.2 billion (US$75.9 billion), identified nanotechnology as one of 10 research themes to fund through its cooperation program. That program supports collaborative projects and accounts for 60 percent of the FP7 budget. FP7 has already invested €265 million (US$378 million) in projects that apply nanotechnology to disease-related research, a field known as nanomedicine. The support so far represents a 31 percent increase compared to what was funded through the nanotechnology theme within the entire FP6, which ran from 2002 to 2006, write Gabellieri and Frima. An additional €55 million went to nanomedicine projects funded through the “health” theme within the FP7. (View a listing of funded projects in targeted nanopharmaceuticals and early diagnostics.)
Although this funding is substantial, especially when it comes to a field that is largely untested, the EU has put in place measures to ensure that the cash is well spent. To apply for a cooperation grant, researchers need to lay out at the proposal stage a detailed work plan with a list of deliverables and milestones to be met during the course of the project as explained in the Guide to Applicants. Once a grant is awarded, the consortium has to report to the funding body every 18 months—or every 12 months for projects receiving more than €10 million. “The consortium has to send a report on the scientific activities, dissemination of the results, management, explanation on the use of the resources,” wrote Gabellieri in an e-mail to ARF. Each project has a coordinator who makes sure that the project is implemented according to schedule. “If a project falls behind schedule, a revised work plan has to be presented to readdress the pending issues, which still have to be in line with the original call and evaluation. If these changes are major, an amendment of the contract is required. In case of major failure, the whole project or the participation of some partners may be terminated,” wrote Gabellieri.
Among the funded projects, Gabellieri and Frima’s article highlights a project dubbed NAD, or Nanoparticles for Therapy and Diagnosis of Alzheimer's Disease. It aims to design nanometer-sized particles that incorporate different combinations of functional groups—from those that target amyloid and gain access into the brain, to imaging contrast agents and chemicals that make the particles more stable—in an effort to find compounds that can slow down the progression of AD. With a budget of €14.37 million (US$20.8 million) over five years, of which €10.92 million comes from the FP7 and the rest from host institutions (such contributions are a requirement of these EU grants), NAD is “one of the larger projects we are funding in nanomedicine,” Gabellieri told ARF.
What is the benefit of applying nanomedicine to AD, the esteemed reader may well ask? In a sense, nanoscale materials have been a part of AD research for a while—that is, in some of the amyloid imaging agents used. But nanomedicine as a discipline unto itself has really taken off in the past decade, mostly in the cancer field. There, a handful of agents has been approved for clinical use, for example, Doxil, in which the drug doxorubicin is bound to liposomes, and hundreds are in clinical trials. In cancer therapy, nanoparticles—which can be organic molecules like lipids or proteins or inorganic ones like gold spheres—are decorated with drugs and other components that can seek out and bind to tumor cells. “Nanoparticles change the biodistribution of a drug to help increase its concentration in tumors,” said Terry Allen, a pharmacologist who works on drug-delivery methods at the University of Alberta, Canada. Nanoparticles provide other advantages, such as protecting bound molecules from degradation. “They can also release drug more slowly over longer periods of time, so that you have to give the drug less often to a patient,” added Allen.
Another application of nanomedicines is the development of imaging agents for tumors. One approach uses semiconductor quantum dots—2 to 10 nanometer-wide crystals that emit light of different color depending on their size—that can be coupled to molecules that bind tumor cells. When used in conjunction with magnetic resonance imaging (MRI), quantum dots can produce higher-contrast images than conventional dyes, although concerns about possible toxicity of these nanoparticles still need to be addressed before they can make their way into the clinic. Quantum dots are also starting to appear in AD research as tools for imaging amyloid-β (Aβ) aggregates (see ARF related news story on Tokuraku et al., 2009) and studying Aβ toxicity (see ARF related news story on Renner et al., 2010).
Given initial promising developments in cancer, more and more researchers are starting to look at Alzheimer’s as a possible indication for nanoscale approaches. “We know a lot about nanoparticles in cancer. It is a natural progression to move this technology to Alzheimer’s, where there is a lack of diagnosis and treatment,” said Tara Spires-Jones at Massachusetts General Hospital, who is applying nanomedicine to the early diagnosis of AD. “We need all the new ideas for therapies that we can get,” said William Klunk of the University of Pittsburgh, Pennsyvania.
Part 2 of this series discusses some of the challenges of nanomedicine in AD and the progress NAD researchers and others have made in tackling them.—Laura Bonetta
This is Part 1 of a two-part series. See also Part 2.
- Quantum Leap? Nanoprobes Track Aβ Aggregation in Real Time
- Aβ Oligomers: A Fatal Attraction for Glutamate Receptors?
- EU Consortium Applies Nanotechnology to Study AD
- Tokuraku K, Marquardt M, Ikezu T. Real-time imaging and quantification of amyloid-beta peptide aggregates by novel quantum-dot nanoprobes. PLoS One. 2009;4(12):e8492. PubMed.
- Renner M, Lacor PN, Velasco PT, Xu J, Contractor A, Klein WL, Triller A. Deleterious effects of amyloid beta oligomers acting as an extracellular scaffold for mGluR5. Neuron. 2010 Jun 10;66(5):739-54. PubMed.
- Gabellieri C, Frima H. Nanomedicine in the European Commission policy for nanotechnology. Nanomedicine. 2011 Oct;7(5):519-20. PubMed.