By Sean Henahan, Access Excellence

SAN DIEGO, CA It may soon be possible to resuscitate gray hair and recover follicles that have gone dormant, suggest the results of a somewhat bizarre experiment conducted by researchers at a small biotechnology company here.

Researchers at AntiCancer, Inc. are primarily engaged in developing new diagnostic and therapeutic modalities for the treatment of cancer. As part of this work, they grow various types of cancer cells on artificial sponge-gel matrices. One day they tried growing normal human skin on the gel matrices. To their surprise, not only did the cells grow, they produced hair.

Having developed a method to cultivate hair-growing skin cells, the next obvious step was to screen for molecules that might modify hair growth. Working along these lines, the researchers found liposomes (synthetic microscopic phospholipid spheres) could be used to selectively andefficiently target molecules to the follicle cells. They have now reported the successful delivery of plasmid DNA coding for the lacZ gene to mouse skin cells. The lacZ gene was chosen as a reporter gene because it produces galactosidase, an enzyme that is easy to detect by staining.

"In our study we were able to selectively target the lacZ reporter gene to the hair follicles of mice after topical application of the gene entrapped in liposomes. These results demonstrate that highly selective, safe gene therapy for the hair process is feasible," said Robert Hoffman, M.D., founder and president of AntiCancer Inc. Topical application of the gene not encapsulated in liposomes did not result in gene transfer. Moreover, no sign of the LacZ gene was observed in the follicles of animals not treated with the liposome-gene combination, he noted.

These findings could lay the groundwork for the treatment of baldness or for methods of artificial darkening of hair that has turned gray with age, using a very safe and relatively straightforward procedure, Hoffman notes. The hair follicle is a complex structure composed of epidermal and dermal cell layers, specialized keratinocytes and hair matrix cells. The matrix cells give rise to the hair shaft.

"These results demonstrate that genes can be targeted selectively to the most important cells of the hair follicle by liposomes representing the most important cells of the hair follicle, by liposomes representing the most selective targeting of a gene observed thus far in vivo," he said. "We have an enemy, hair follicle disease, and Dr. Hoffman has invented a gun with which to fight that enemy," said Dr. Leonid B. Margolis, liposome expert and researcher at the National Institutes of Health in Bethesda, Md. "He has demonstrated that the gun works by firing blanks at the hair follicles. What remains for us to do is to develop the ammunition that will make the gun useful in the fight against hair loss." This new highly selective method of targeting genes could lead to targeting hair matrix cells and possibly follicle stem cells to restore hair color. The tyrosinase gene could be a suitable candidate for this application. Preliminary research suggests this enzyme could reactivate pigment production in the follicles of people with gray hair.

The company is also investigating the idea of using liposomes containing drugs to prevent hair loss caused by cancer chemotherapy. This approach may be the first to bear fruit (hair?) with some experimental data suggesting that pre-treated chemotherapy patients may be able to keep up to 80% of their hair. Scientists at AntiCancer, Inc. have already developed a method for delivering melanin, the chemical that gives hair its color, to hair follicles. This would allow coloration of hair without the tell-tale off-color roots. It is possible a cosmetic product could make it to market within a couple of years, said Hoffman. Liposome-based gene and drug therapies could ultimately offer hope to people with hereditary alopecia, the most common type of baldness that affects 80 million men and women in the US alone. Success in this area will depend on the identification of genes involved in both the growth and loss of hair.

Nature Medicine, Vol.1, No.7, 7/95,; Hoffman et al; pp 705-706..

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