Biotech Strategy Blog

Commentary on Science, Innovation & New Products with a focus on Oncology, Hematology & Cancer Immunotherapy

Posts tagged ‘MRI’

Changes in brain structure, function and molecular processes occur several years before clinical symptoms of Alzheimer’s disease (AD) become apparent.

The big question then, is can you detect patients who are cognitively normal, but will go on to develop AD before they show symptoms, i.e. pre-symptomatic patients?  The answer is “Yes” according to results published in the April 19, 2011 issue of Neurology by Brad Dickerson and colleagues.

In this small study, the team of researchers from two centers (Massachusetts General Hospital and Rush University in Chicago) followed a small sample of cognitively normal (CN) subjects over time with magnetic resonance imaging (MRI) and then sought to identify what structural changes had taken place in those subjects who were initially cognitively normal, but went on to develop AD, on average 11.1 years later.

The researchers found that changes in brain cortical thickness were associated with AD:

AD-signature cortical thinning in CN-AD converters in both samples was remarkably similar, about 0.2 mm (p < 0.05)

They concluded that:

By focusing on cortical regions known to be affected in AD dementia, subtle but reliable atrophy is identifiable in asymptomatic individuals nearly a decade before dementia, making this measure a potentially important imaging biomarker of early neurodegeneration.

Some of the limitations of this research and questions that come to mind are:

  • Small sample size: only 8 individuals who developed AD and 25 in the cognitively normal control group.
  • Reproducibility: the 0.2mm difference seen is small and the extent to which other centers may be able to reproduce this measurement is uncertain
  • Accuracy of detection: in any screening tool the issue of false positives and negatives arises i.e. in a larger sample size will there be a margin for error that results in some people being included in the pre-symptomatic AD group, when they may be normal?  Also will the proposed measurement remain valid in a large population of patients with other disease symptoms and chronic illnesses?
  • Validity of biomarker: are the changes in cortical thickness causally linked to AD or just an incidental correlation i.e. is this a valid biomarker?

Brad Dickerson in the excellent Neurology podcast available with this publication clearly sees this currently as a research tool, especially given the requirement for considerable computer power to make these types of cortical measurements in the brain.  The podcast interview is well worth listening to.

The MRI biomarker proposed by Dickerson is therefore not something that is really applicable to screen the general population at the moment.

However, the promise from this and other biomarker research is that at some point in the not too distant future we will be able to detect those at risk of developing AD. Those patients could then be given neuroprotective drugs that may delay the onset of the clinical symptoms of AD such as memory loss and cognitive impairment.

Biomarkers that identify those at risk of developing AD will also be useful as inclusion and screening tools for clinical trials of drugs aimed at slowing disease progression in pre-symptomatic patients.

Alzheimer’s disease has been called “The challenge of the Second Century,” we still have a long way to go before this is overcome.

Story Source:  BBC Health

ResearchBlogging.orgDickerson, B., Stoub, T., Shah, R., Sperling, R., Killiany, R., Albert, M., Hyman, B., Blacker, D., & deToledo-Morrell, L. (2011). Alzheimer-signature MRI biomarker predicts AD dementia in cognitively normal adults Neurology, 76 (16), 1395-1402 DOI: 10.1212/WNL.0b013e3182166e96

Innovation in drug delivery presents opportunities for biotechnology companies, and is an area I expect we will see major leaps forward through nanotechnology.

Nanotechnology is the application of science and engineering to materials that are between 1 and 100 nanometers (nm) in size.  The Environment Protection Agency (EPA) defines nanotechnology as “the creation and use of structures, devices, and systems that have novel properties and functions because of their small size.”

1nm is one-billionth of a meter.  To put this in context, 1nm is one seven-thousandth of the width of a red blood cell or one eighty-thousandth of the width of a human hair. These are unimaginably small materials that are engineered to operate at the molecular and atomic level.

What’s more, there are now more than 1000+ consumer products on the market that utilize nanotechnology from the titanium particles in sunscreens to the silver contained in advanced first aid strips/plasters.  Nanotechnology will impact more than $2.5 trillion of manufactured goods by 2015.

Lux Research predicts that by 2014, 16% of manufactured goods in healthcare and life sciences will include nanomaterials.

To date, the United States leads the way in the fast evolving field of nanotechnology.  Between 2001 and 2010, the U.S. Government invested $12.4 billion in nanoscale science, engineering and technology through the U.S. National Nanotechnology Initiative (NNI).

The National Cancer Institute’s “NCI Alliance for Nanotechnology in Cancer” has an excellent website that outlines the potential impact of nanotechnology.

Some of the promising new cancer diagnostics and therapies based on nanotechnology include:

  • Positron Emission Tomography (PET) imaging agents that can be used to assess the responsiveness of tumors to chemotherapy
  • Chemically engineered adenovirus nanoparticle that stimulates the immune system. This is in phase 1 trials for chronic lymphocytic leukemia (CLL).
  • Cyclodextrin-based nanoparticle that encapsulates a small-interfering RNA (siRNA) agent that shuts down a key enzyme in cancer cells
  • CRLX101, a cyclodextrin-based polymer conjugated to camptothecin is in clinical trials with solid tumor patients
  • A nanoparticle based magnetic resonance imaging (MRI) contrast agent that binds to αvβ3-intregrin, a protein found on newly developed blood vessels associated with tumor development. This is in early clinical trials
  • Technology for the detection of cancer biomarkers such as prostate specific antigen (PSA)
  • Use of carbon nanotubes to improve colorectal cancer imaging.

Emerging companies such as Bind Biosciences are focusing on targeting cancer, inflammatory, cardiovascular diseases and infectious diseases with therapeutic nanoparticles.  Their lead product BIND-014 is currently in phase 1 development.

Innovations in nanotechnology will continue to present new product opportunities for biotechnology, pharmaceutical, medical imaging and diagnostics companies, and should be on everyone’s radar.


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