Source: Thailand Medical News Jan 23, 2020 4 years, 9 months, 3 weeks, 1 day, 2 hours, 14 minutes ago
Researchers from the University of Pittsburgh School of Medicine have created a biodegradable nerve guide ie a polymer tube filled with growth-promoting protein that can regenerate long sections of
damaged nerves, without the need for transplanting stem cells or a donor nerve.
Dr Lauren Kokai, Ph.D., (left) developed the technology used for this project when she was a graduate
studying under Dr Kacey Marra, Ph.D.,Credit: UPMC
To date, the technology has been tested in monkeys, and the results of those experiments appeared today in
Science Translational Medicine.
Senior author Dr Kacey Marra, Ph.D., Professor of Plastic Surgery at Pitt and core faculty at the McGowan Institute for Regenerative Medicine told
Thailand Medical News, "We're the first to show a
nerve guide without any cells was able to bridge a large, 2-inch gap between the
nerve stump and its target muscle. Our guide was comparable to, and in some ways better than, a
nerve graft."
A cross-section image of the nerve conduit embedded in microspheres. Credit: N.B. Fadia et al.,
Science Translational Medicine (2019)
Typically, half of wounded American soldiers return home with injuries to their arms and legs, which aren't well protected by body armor, often resulting in
damaged nerves and disability. Among civilians, car crashes, machinery accidents, cancer treatment, diabetes and even birth trauma can cause significant
nerve damage, affecting more than 20 million Americans.
Though peripheral
nerves can regrow up to a third of an inch on their own, but if the damaged section is longer than that, the
nerve can't find its target. Often, the disoriented
nerve gets knotted into a painful ball called a
neuroma.
Currently, the most common treatment for longer segments of
nerve damage is to remove a skinny sensory
nerve at the back of the leg which causes numbness in the leg and other complications, but has the least chance of being missed, chop it into thirds, bundle the pieces together and then sew them to the end of the
damaged motor
nerve, usually in the arm. But only about 40 to 60% of the motor function typically returns.
Dr Marra explained to Thailand
Medical News, "It's like you're replacing a piece of linguini with a bundle of angel hair pasta. It just doesn't work as well."
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An image of the 5.2-cm nerve guide. Credit: N.B. Fadia et al., Science Translational Medicine (2019)
Dr Marra's
nerve guide returned about 80% of fine motor control in the thumbs of four monkeys, each with a 2-inch
nerve gap in the forearm.
The new
nerve guide is made of the same material as dissolvable sutures and peppered with a growth-promoting protein, the same one delivered to the brain in a recent Parkinson's trial which releases slowly over the course of months.
The research experiment had two controls: an empty polymer tube and a
nerve graft. Since monkeys' legs are relatively short, the usual clinical procedure of removing and dicing a leg
nerve wouldn't work. So, the scientists removed a 2-inch segment of
nerve from the forearm, flipped it around and sewed it into place, replacing 'linguini with linguini,' and setting a high bar for the nerve guide to match.
It was observed that functional recovery was just as good with Dr Marra's guide as it was with this best-case-scenario graft, and the guide outperformed the graft when it came to restoring
nerve conduction and replenishing Schwann cells ie the insulating layer around nerves that boosts electrical signals and supports regeneration. In both scenarios, it took a year for the
nerve to regrow. The empty guide performed significantly worse all around.
As a result of these promising results in monkeys, Dr Marra wants to bring her
nerve guide to human patients. She's working with the Food and Drug Administration (FDA) on a first-in-human clinical trial and spinning out a startup company, AxoMax Technologies Inc.
Dr Marra further added, "There are no hollow tubes on the market that are approved by the FDA for
nerve gaps greater than an inch. Once you get past that, no off-the-shelf tube has been shown to work. That's what's amazing here."
Reference: N.B. Fadia el al., "Long-gap peripheral nerve repair through sustained release of a neurotrophic factor in nonhuman primates," Science Translational Medicine (2020). stm.sciencemag.org/lookup/doi/ … scitranslmed.aav7753