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In Vivo Use of Targeted Toxins

Q: Can you use targeted toxins in vivo?

A: Yes, Molecular Neurosurgery is designed as a tool for in vivo use.

Q: How do you recommend administration of the targeted toxin?

A: There are several ways to administer the toxins depending on the cells being targeted:

1. Direct intraparenchymal pressure microinjection can be used to deliver the targeted toxin directly to target cells. This approach has been used successfully with several toxins, including SP-Saporin (SP-SAP, Cat. #IT-07), in the striatum to kill striatal interneurons that express the NK-1 receptor. Long slow infusions (0.1 µl/min) are probably the best way to do intraparenchymal injections. [1]

2. Targeted toxins can also be injected into terminal fields and retrogradely transported to the cell bodies. This approach has been used successfully to selectively destroy locus coeruleus noradrenergic neurons that project to the olfactory bulb by injecting anti-DBH-saporin (Anti-DBH-SAP, Cat. #IT-03) into the olfactory bulb.[2]

Intracortical injections of 192-Saporin (192-IgG-SAP, Cat. #IT-01) also have been used to destroy cholinergic basal forebrain neurons projecting to the injected patch of cortex.[3]

Lumbar subarachnoid injections of SP-Saporin (SP-SAP, Cat. #IT-07) can destroy lamina I neurons in the dorsal horn that express the NK-1 receptor.[4]

3. Lastly, SP-Saporin (SP-SAP, Cat. #IT-07) has also been applied directly to the surface of the spinal cord to kill lamina I neurons expressing NK-1 receptor. In all cases, pilot studies to determine optimal toxin dose and injection parameters are recommended.

See: Targeted Toxins

References

  1. Wiley RG et al. Destruction of neurokinin-1 receptor expressing cells in vitro and in vivo using substance P-saporin. Neurosci Lett 230:97-100, 1997.
  2. Blessing WW et al. Destruction of locus coeruleus neuronal perikarya after injection of anti-dopamine-beta-hydroxylase immunotoxin into the olfactory bulb of the rat. Neurosci Lett 243:85-88, 1998.
  3. Wiley RG et al. Immunolesioning: Selective destruction of neurons using immunotoxin to rat NGF receptor. Brain Res 562:149-153, 1991.
  4. Mantyh PW et al. Inhibition of hyperalgesia by ablation of lamina I spinal neurons expressing the substance P receptor. Science 278:275-279, 1997.