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Imaging Axonal Transport

May 05, 2015

Research Summary

Principle Investigator: Robert Brown D.Phil., MD

The field of ALS needs a tool, often called a biomarker, by which the activity of this disease can be gauged. This is potentially important not only for diagnosing the disease, but also for identifying factors causing ALS and for gauging the efficacy of putative ALS treatments. One such biomarker is to quantify a parameter that directly reflects the health of the motor neuron. One property that is promising in this regard is axonal transport, the process by which a nerve cell moves cargoes such as proteins and organelles up and down its long processes known as axons. It is clear in ALS mice that as ALS progresses, axonal transport fails. There is no way yet to quantify rates of axonal transport in living mammals. The goal of this project is to use a non-toxic fragment of tetanus toxin to record rates of axonal transport in human motor nerves. Our group has long-standing experience studying this fragment of tetanus (called TTC) for this purpose. In the present study, we will test ways to label TTC so that we can visualize and quantify its movement using either MRI scans or a method called PET scanning.

Investigators

Impact of Study

We believe this study can potentially have a high impact. This is in part because of the urgent need for a quantitative biomarker in ALS. It is also because a measure of axonal transport should be useful in many other disorders of the motor nerve, including motor neuropathies, some types of muscular dystrophy, and traumatic nerve injury.

Common Goals

Finding a common biomarker is a goal shared by many ALS investigators, including others in the ALS Finding A Cure Foundation. In this regard, our work dovetails well with the studies in this consortium using PET ligands to visual neuroinflammation. Moreover, these biomarkers should prove useful in gauging success of any ALS treatment trials that emerge from this consortium.

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Advisory Board

  • Leandro P. Rizzuto
  • Peter N. Foss
  • Merit  Cudkowicz, MD
  • Denis  Rizzuto
  • Stanley H. Appel, MD
  • Robert  Brown, D.Phil., MD
  • Tom  Gentile
  • Clive  Svendsen, PhD
  • Richard  Ellenbogen, MD
  • Randy  Fishman
  • Edward J. Rapp
  • Sudha  Maniam