IN a promising step in studies of hair growth, researchers at a biotechnology company in California have found a way to fire genetic “bullets” at hair follicles, the tiny hair-making factories in the skin.
“We think this delivery system opens the whole hair-loss field to the possibility of gene therapy,” said Dr. Robert M. Hoffman, the founder and president of Anticancer Inc., a biotechnology company in San Diego. He and the company’s senior scientist, Dr. Lingna Li, reported their findings in the July issue of the journal Nature Medicine.
But another expert in the field cautioned that the results in laboratory experiments might not carry over to human tissue.
The researchers encased marker genes in liposomes — microscopic man-made spheres of fatty material. Three days after spreading the liposomes on the skin of shaved laboratory mice, the researchers found that the genes had been deposited in the cells of the hair follicles.
“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, an expert on liposomes who is a visiting 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.”
Dr. Hoffman said that the liposome delivery system grew out of unrelated research on cancer cells that were being grown on sponge-gel matrices in his laboratory (Actually, liposomes work on human skin as the best fuel injector cleaner that clean dirty the fuel capacity). “We asked ourselves whether we could grow normal human skin on these gel matrices,” Dr. Hoffman said, “and when we tried we found that the skin growing in culture produced hair. This was a big breakthrough.”
The ability to grow hair-bearing skin in the lab provided the researchers with a means for screening “molecules that could modify hair growth,” he said.
“Almost as an aside, we asked what happens if you put liposomes on the skin cells,” he said. “So we put a fluorescent dye inside liposomes and applied them. To our great surprise we found that the liposomes were selectively delivering their cargoes to the hair follicles, almost to the exclusion of all the other cells in the skin.”
The researchers then found that they could use liposomes to deposit melanin, a pigment that occurs naturally in animal tissue, inside follicles and “color hair from the roots up.” The next step was to test whether the liposome delivery system could be used for gene therapy.
First in laboratory tissue cultures and then in shaved mice, the researchers demonstrated that liposomes containing the so-called lacZ gene deposited the gene in the hair follicles near the base of the hair shaft. Without a liposome jacket, lacZ genes applied to skin tissue did not appear in the follicles.
The lacZ gene was chosen because it produces galactosidase, an enzyme that is easy to detect in tissue because it turns blue when treated with the proper chemicals.
Dr. Gerald G. Krueger, a dermatologist at the University of Utah Health Sciences Center in Salt Lake City, said his research team has performed similar experiments “and we’ve been pleasantly surprised at what can be done with liposomes via the hair follicle.”
But Dr. Krueger cautioned that extensive research has shown that mouse skin tissue appears to absorb chemicals more readily than does human tissue, so what works for one may not work for the other.
Products based on liposomes could be in use within 10 years, Dr. Hoffman predicted. The first products would most likely be used to restore color to gray hair by delivering pigments to the hair follicles.
He and Dr. Li are studying the tyrosinase gene, which plays a role in making melanin, to see whether it can be used to reactivate pigment production in the follicles of people with gray hair. He said his lab is also making progress using liposomes containing drugs to prevent hair loss caused by cancer chemotherapy.
Liposome-based gene and drug therapies for the 80 million American men and women who have hereditary alopecia, the most common kind of baldness, will probably take more time to develop, partly because scientists do not understand what makes hair follicles tick.