Sunday, 7 July 2013

Imaging remyelination

Wu C, Zhu J, Baeslack J, Zaremba A, Hecker J, Kraso J, Matthews PM, Miller RH, Wang Y.Longitudinal PET imaging for monitoring myelin repair in the spinal cord. Ann Neurol. 2013 Jul 1. doi: 10.1002/ana.23965. [Epub ahead of print]

Objective: Novel therapeutic interventions aimed at myelin repair are now under development for neuroprotection as well as functional recovery of patients with multiple sclerosis (MS). However, development of myelin-repair therapy necessitates a non-invasive approach for measuring changes in myelin content in vivo in a quantitative fashion not yet possible using MRI. For this reason, we developed a novel PET probe, termed [11 C]MeDAS, that is capable of longitudinally imaging CNS myelin content. Methods: The binding properties of [11 C]MeDAS for myelin were systematically evaluated by in vitro and in situ fluorescent staining of the spinal cord and the brain, and by in vivo competitive blocking studies. Longitudinal PET studies were conducted in three rat models involving acute focal neuroinflammation in the brain, LPC-induced focal demyelination in the spinal cord, and experimental autoimmune encephalomyelitis (EAE). Image-guided myelin repair therapy was conducted in an LPC rat model using a mesenchymal stem cell-based hepatocyte growth factor (HGF). Biodistribution and acute toxicity studies of [11 C]MeDAS were also conducted. Results: MeDAS selectively stains myelin in the spinal cord and brain. Neuroinflammation did not affect [11 C]MeDAS uptake in the brain as long as the myelin sheaths remained intact. Longitudinal PET studies in LPC and EAE rat models demonstrate that [11 C]MeDAS uptake changes correlate with associated myelin loss in the spinal cord. Furthermore, using [11 C]MeDAS-PET, the efficacy of myelin-repair therapy with HGF was longitudinally monitored in vivo
Interpretations: [11 C]MeDAS-PET is a promising imaging marker for monitoring myelin pathology in vivo, future applications of which in humans should be achievable.

PET is positron emission topography which is a scanner like an MRI which can detect radioactive compounds. The molecular weight of carbon is 12. There are three naturally occurring isotopes, with 12C and 13C being stable, while 14C is radioactive, decaying with a half-life of about 5,730 years. 12C accounting for 98.89% of carbon; it contains six protons, six neutrons and six electrons. Carbon-11 or 11C is a radioactive isotope of carbon that decays to boron-11. This decay mainly occurs due to positron emission. This study looks at a myelin labelling compound called MeDAS. They then make it radioactive using a cyclotron. The Cyclotron beams are used to bombard other atoms to produce short-lived positron-emitting isotopes suitable for PET imaging.  They use animals to show that myelin can be imaged over time. This type of tool would be invaluable to monitor MS and importantly to monitor repair as MRI has yet to convincing monitor myelin. At present the onlyway to monitor it is using electrophysiology so see how nerve conduction is affected.

4 comments:

  1. Mouse,

    Many thanks - I was thinking about remyelination treatments this morning.

    Make sure you have a break and make the most of this lovely weather. I imagine Prof G is somewhere nice with a piña colada in his hand. You're busy in the lab!

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    1. This hot weather is playing havoc with our MS symptoms. I was in the gym yesterday and even with the air conditioning on full blast, it was baking. When I complained they informed me that the hot air outside is killing the mechanics of the A/C machine. It is so typically British for nothing to actually work the way it's supposed to, with hot weather either crippling the nation, or when it's cold, freezing conditions causing things to breakdown. I bet things like this never happen in other developed European nations or in places like Texas and Toronto. Heck, it's only in the high 20s outside yet basic technological functionality still evades us! Britain is such an embarrassment at times.

      Rant, over...

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    2. Britain is also an embarrassment when it comes to treating MS with DMTs. We have the lowest penetration of DMTs amongst the developed countries and we can't use the drugs in CIS. I suspect NICE will put a spanner in the works when it comes to Lemtrada (alemtuzumab) as well.

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  2. Even if remyelination can be accomplished it is still not clear if nuerodegeneration will be inevitable because the remeylinated axons require more energy than normal myelinated axons. It is this increase in energy demand that may result in progressive disease over time:

    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3122369/

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