Protein in human hair shows promise for regenerating nerves

January 11, 2008

A protein found in human hair shows promise for promoting the regeneration of nerve tissue and could lead to a new treatment option when nerves are cut or crushed from trauma.

In the current issue of Biomaterials, scientists from Wake Forest University School of Medicine reported that in animal studies the protein keratin was able to speed up nerve regeneration and improve nerve function compared to current treatment options.

“We found that the nerve repair happened more quickly and consistently, and that functional recovery was higher,” said Mark Van Dyke, Ph.D., senior author and an assistant professor of regenerative medicine. “The fact that we were able to accomplish this with gels made from keratin is pretty remarkable.”

Current treatments for repairing damaged nerves include microsurgery to sew two ends of the nerve together, using a nerve from another part of the body to replace a damaged section, or placing an empty tube between the cut ends so that nerve fibers can grow through it and back into the muscle.

Grafting a nerve from another part of the body is usually the most effective option, but it creates another injury site and isn’t possible in all patients. The tubes, known as nerve guidance conduits, cannot be used in gaps longer than three or four centimeters. In addition, nerve regeneration with this method is not always successful. For example, after about age 17, nerves don’t regenerate as well.

Laboratory scientists have tried placing natural materials, such as collagen, into the conduits to promote nerve regeneration. Van Dyke’s team was the first to use keratin, which is believed to contain molecules that regulate cell behavior.

The scientists collected human hair from a local barber shop and chemically processed it to remove the keratin. They purified the keratin protein and used it to form gels that were then used to fill the nerve guidance conduits. They studied how keratin affects the activity of Schwann cells, which play a vital role in nerve regeneration. These cells produce signals that tell nerve cells to begin regenerating and “remodel” the blood clot that has formed so that nerve cells can grow across it.

“By using keratin to activate these cells, we’re trying to tap into the natural healing cascade,” said Van Dyke. “We believe that keratin helps amp up Schwann cell activity and give the nerve regeneration process a head start.”

The laboratory studies showed that keratin activated Schwann cells and increased their proliferation and migration. Next, the scientists used a keratin-filled tube to attempt to repair a 4 millimeter nerve gap in mice -- a fairly significant gap considering the size of the animal.

The results from these animals were compared with animals treated with an empty nerve guidance conduit and with animals treated with a nerve graft.

After six weeks, 100 percent of the animals in the keratin and nerve graft groups showed visible nerve regeneration across the gap, compared to only 50 percent who got the empty conduit. The speed of repair was best in the keratin group.

The scientists then tested the function of the regenerated nerve. The speed of nerve impulses was best in the keratin group. The amount of signal that got through the nerve was better in the keratin group than in the empty tube group. The study was recently highlighted in the journal Science.

“The results suggest that a conduit filler derived from hair keratins can promote an outcome comparable to a grafted nerve,” said Van Dyke.

In the study, the nerve function did not translate into recovery of muscle function, but the scientists suspect they may have tested too early, before the nerve had time to regenerate to the muscle. It is known that muscle function recovery lags behind nerve recovery. Future studies will focus on regeneration across larger gaps and will test whether nerve regeneration results in a return of muscle function.

Bioavailability of Curcumin: Problems and Promises

November 21, 2007

Mol Pharm. 2007 Nov 14

Anand P, Kunnumakkara AB, Newman RA, Aggarwal BB.

Cytokine Research Laboratory and Pharmaceutical Development Center, Department of Experimental Therapeutics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030

Curcumin, a polyphenolic compound derived from dietary spice turmeric, possesses diverse pharmacologic effects including anti-inflammatory, antioxidant, antiproliferative and antiangiogenic activities. Phase I clinical trials have shown that curcumin is safe even at high doses (12 g/day) in humans but exhibit poor bioavailability. Major reasons contributing to the low plasma and tissue levels of curcumin appear to be due to poor absorption, rapid metabolism, and rapid systemic elimination.

To improve the bioavailability of curcumin, numerous approaches have been undertaken. These approaches involve, first, the use of adjuvant like piperine that interferes with glucuronidation; second, the use of liposomal curcumin; third, curcumin nanoparticles; fourth, the use of curcumin phospholipid complex; and fifth, the use of structural analogues of curcumin (e.g., EF-24). The latter has been reported to have a rapid absorption with a peak plasma half-life.

Despite the lower bioavailability, therapeutic efficacy of curcumin against various human diseases, including cancer, cardiovascular diseases, diabetes, arthritis, neurological diseases and Crohn's disease, has been documented. Enhanced bioavailability of curcumin in the near future is likely to bring this promising natural product to the forefront of therapeutic agents for treatment of human disease.

Oral Curcumin Mitigates the Clinical and Neuropathologic Phenotype of the Trembler-J Mouse: A Potential Therapy for Inherited Neuropathy

August 07, 2007

Author(s) Mehrdad Khajavi, Kensuke Shiga, Wojciech Wiszniewski, Feng He, Chad A. Shaw, Jiong Yan, Theodore G. Wensel, G. Jackson Snipes, and James R. Lupski

The American Journal of Human Genetics, volume 81 (2007), page 000
DOI: 10.1086/519926

Abstract

Mutations in myelin genes cause inherited peripheral neuropathies that range in severity from adult-onset Charcot-Marie-Tooth disease type 1 to childhood-onset Dejerine-Sottas neuropathy and congenital hypomyelinating neuropathy. Many myelin gene mutants that cause severe disease, such as those in the myelin protein zero gene (MPZ) and the peripheral myelin protein 22 gene (PMP22), appear to make aberrant proteins that accumulate primarily within the endoplasmic reticulum (ER), resulting in Schwann cell death by apoptosis and, subsequently, peripheral neuropathy.

We previously showed that curcumin supplementation could abrogate ER retention and aggregation-induced apoptosis associated with neuropathy-causing MPZ mutants.

We now show reduced apoptosis after curcumin treatment of cells in tissue culture that express PMP22 mutants. Furthermore, we demonstrate that oral administration of curcumin partially mitigates the severe neuropathy phenotype of the Trembler-J mouse model in a dose-dependent manner.

Administration of curcumin significantly decreases the percentage of apoptotic Schwann cells and results in increased number and size of myelinated axons in sciatic nerves, leading to improved motor performance. Our findings indicate that curcumin treatment is sufficient to relieve the toxic effect of mutant aggregation-induced apoptosis and improves the neuropathologic phenotype in an animal model of human neuropathy, suggesting a potential therapeutic role
in selected forms of inherited peripheral neuropathies.

Curis Achieves Milestone under Wyeth Collaboration

April 02, 2005

Curis, Inc. (NASDAQ: CRIS), a therapeutic drug development company, today announced that it has achieved a development milestone under a collaboration with one of its corporate partners, Wyeth Pharmaceuticals, a division of Wyeth (NYSE: WYE). The milestone is based on Wyeth's and Curis' continued progress in preclinical development of Hedgehog pathway agonists for the treatment of stroke, neurological and other disorders. The milestone will trigger a modest payment from Wyeth to Curis in accordance with the terms of their 2004 agreement.

The Hedgehog signaling pathway regulates the normal development of the brain and spinal cord. Wyeth and Curis are collaborating to develop several promising small molecule agonist compounds that can activate the Hedgehog signaling pathway and thereby promote nervous system repair. Many of these small molecules are orally available and can enter into the brain and spinal cord, thus making them an attractive new class of drug development candidates for neurological disorders.

Daniel Passeri, President and Chief Executive Officer of Curis, said, "We are very pleased with the progress that has been made with Wyeth in the Hedgehog agonist program. The achievement of this milestone is an important next step in the path of bringing these promising drug candidates towards clinical trials and ultimately to the patients who need them."

Neuren And Metabolic Collaborate To Develop Range Of Nerve Repair Compounds With Support From NZ Government

March 07, 2005

Neuren Pharmaceuticals Ltd (Neuren) and Metabolic Pharmaceuticals Ltd (Metabolic) today announced that the two companies have agreed to collaborate to co-develop Neuren's class of Neuro-regenerative Peptides (NRPs) for the treatment of degenerative conditions such as peripheral neuropathy, motor neuron disease and repairing the brain or nerves after injuries such as spinal cord injury. The parties will jointly develop the NRPs project with all intellectual property and commercial outcomes to be equally shared.

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