Fluorescent Peptides Help Nerves Glow in Surgery

What is never talked much aboutis the level of nerve damage involved in surgery.  It is the major side effect of surgery and I suspectthat there is some in all but the simplest operations.

The scariest type of operation toface is spinal work for that exact reason. One can often only hope that the cure is no worse that the ailment.  A painful back is awful, but been confined toa wheelchair is equally unpleasant.  Theprobability of damage is actually far too high and likely near inevitable atsome level.

Now we have a tool that allowsthe surgeon to see the risk and avoid it. This obviously very good news fro all future surgery.

Fluorescent Peptides Help Nerves Glow in Surgery

Released: 2/4/2011 4:00 PM EST 

Embargo expired: 2/6/2011 1:00 PM EST

Source: Universityof California, San Diego Health Sciences

http://www.newswise.com/articles/view/573146/?sc=dwhn

Newswise — Accidental damage to thin or buried nerves during surgerycan have severe consequences, from chronic pain to permanent paralysis.Scientists at the University of California, San Diego Schoolof Medicine may have found a remedy: injectable fluorescent peptides that causehard-to-see peripheral nerves to glow, alerting surgeons to their location evenbefore the nerves are encountered.

The findings are published in the Feb. 6 advance online edition of thejournal Nature Biotechnology.

Nerve preservation is important in almost every kind of surgery, but itcan be challenging, said Quyen T. Nguyen, MD, PhD, assistant professor of Headand Neck Surgery and the study’s corresponding author. “For example, if thenerves are invaded by a tumor. Or, if surgery is required in the setting oftrauma or infection, the affected nerves might not look as they normally would,or their location may be distorted.”

Nguyen and colleagues at the Moores Cancer Centerdeveloped and injected a systemic, fluorescently labeled peptide (a proteinfragment consisting of amino acids) into mice. The peptide preferentially bindsto peripheral nerve tissue, creating a distinct contrast (up to tenfold) fromadjacent non-nerve tissues. The effect occurs within two hours and lasts forsix to eight hours, with no observable effect upon the activity of thefluorescent nerves or behavior of the animals.

“Of course, we have yet to test the peptide in patients, but we haveshown that the fluorescent probe also labels nerves in human tissue samples,”Nguyen said. Interestingly, fluorescence labeling occurs even in nerves thathave been damaged or severed, provided they retain a blood supply. Thediscovery suggests fluorescence labeling might be a useful tool in futuresurgeries to repair injured nerves.

Currently, the ability to avoid accidental damage to nerves duringsurgery depends primarily upon the skill of the surgeon, and electromyographicmonitoring. This technique employs stimulating electrodes to identify motornerves, but not sensory nerves such as the neurovascular bundle around theprostate gland, damage of which can lead to urinary incontinence and erectiledysfunction following prostate surgery.

The new study complements earlier work in surgical molecular navigationby Nguyen and Roger Tsien, PhD, Howard Hughes Medical Institute investigator,UCSD professor of pharmacology, chemistry and biochemistry, a co-author of thepaper and co-winner of the 2008 Nobel Prize in chemistry for his work on greenfluorescent protein. In 2010, for example, the scientists and colleaguespublished papers describing the use of activated, fluorescent probes to tagcancer cells in mice. The ultimate goal of their work is to help surgeonsidentify and remove all malignant tissues by lighting up cancer cells, thusreducing the chance of recurrence and improving patient survival rates.

“The analogy I use is that when construction workers are excavating,they need a map showing where the existing underground electrical cables areactually buried, not just old plans of questionable accuracy,” said Tsien.“Likewise when surgeons are taking out tumors, they need a live map showingwhere the nerves are actually located, not just a static diagram of where theyusually lie in the average patient.”

The researchers continue to refine their probes in animal models andprepare for eventual human clinical trials.

Co-authors of the paper include Michael A. Whitney and Beth Friedman,Department of Pharmacology, UCSD; Jessica L. Crisp, Department of Chemistry andBiochemistry, UCSD; Linda T. Nguyen, Division of Otolaryngology-Head and NeckSurgery, UCSD; Larry A. Gross and Paul Steinbach, Howard Hughes MedicalInstitute, UCSD.

These studies were supported by funding from the Howard Hughes MedicalInstitute, the Burrough-Wellcome Fund and grants from the National Institutesof Health (Awards #5K08EB008122 and #NS27177).

Quyen Nguyen, Michael Whitney and Roger Tsien are inventors of atechnology that has been licensed by the University to Avelas Biosciences andhas an equity interest in the company. The terms of this arrangement have beenreviewed and approved by the Universityof California, San Diego in accordance with its conflict ofinterest policies.