Ever since Delilah tonsured Samson's luxuriant locks, circa 1620B.C., a full head of hair has stood for strength, in popular perception,compared to a bare pate.
Male-pattern baldness (androgenetic alopecia) is an inherited loss ofscalp hair that affects _ indeed, afflicts _ men more than women.So do most of the myriad other causes of denuded heads. In females,hair tends to thin rather than vanish outright.
Hair restoration nowadays remains big business. Toupees sell briskly.Hair transplants are in demand. And when the UpjohnPharmaceutical Co., of Kalamazoo, Mich., discoveredserendipitously a decade ago that its blood-pressure drug, minoxidil,caused hair to sprout on bare scalps, that product took off on themarket.
The 1970s and 1980s have also seen a new and more distressingcause of hair loss, this one unisex. A side-effect of cancerchemotherapy is scalp hair that comes out by the handful.
Thus, when AntiScience Inc., of San Diego, let it be known last weekthat it had taken the first in vivo step toward developing gene therapyfor baldness, press and television covered the story as a newsworthymedia event.
The company's president, Robert Hoffman, is senior author of apaper on the subject that appears in the just-published July issue ofNature Medicine. Its title: "The feasibility of targeting selective genetherapy of the hair follicle."
Liposomes Lay Demo-Model Gene Right On In Vivo Target
Hoffman reported transferring a specific gene, lacZ, into the hairfollicles of mice, via liposomes, fatty bubbles a micron in diameter,as delivery vehicles. That DNA sequence, he explained to BioWorldToday, has nothing to do with hair growth. It served only as areporter gene, a demonstrator model, to verify that his liposomeswere capable of landing their DNA cargo exclusively in the hair-forming hair matrix cells of the follicle bulbs, and at an adjacent sitethought to contain the follicle stem cells.
He and his team placed the gene-laden liposomes topically on themouse's' skin. Control animals received naked lacZ genes,administered without liposome vectors.
Blue staining of the X-gal substrate confirmed expression of theliposome-entrapped galZ at the target site. Sequences applied nakeddid not stain or express.
"Surely," Hoffman observed, "now that we've shown the feasibilityof gene therapy in the hair process, I think there's going to be a bigrace for therapeutic hair genes."
Like tangoing, it takes two participants to perform gene therapy _ avector and a gene. AntiCancer's paper validates the liposomedelivery system. So far, no company has admitted isolating a hair-growth gene. "I think there are some interesting candidates outthere," Hoffman surmised. "They just haven't been tested."
His own company, he conceded, has "some interesting leads," whichhe expects to reveal "reasonably soon." Any rival genes that surface,Hoffman cautioned competitors, "will have to use our technology toapply them."
A pair of prime contenders two years ago were SequanaTherapeutics, of LaJolla, Calif., and Alopex Pharmaceuticals Inc.,Ridgewood, N.J. They formed a collaboration to map genes for male-pattern baldness and abnormal hair growth. (See BioWorld Today,Sept. 13, 1993, p. 1.)
Sequana contracted to sequence such genes; Alopex to develop hair-modulating therapies. However, the latter firm has disappeared, andSequana's interest in hair apparently waned concomitantly.
In Nature Medicine, Hoffman stated baldly: "These resultsdemonstrate that genes can be selectively targeted to the mostimportant cells of the hair follicle, by liposomes representing themost selective targeting of a gene observed thus far in vivo."
Liposomologist Daniel Yarosh, president of Applied Genetics, Inc. inFreeport, N.Y., ratifies this claim. "That's extremely plausible," hetold BioWorld Today. In fact, we and others have observed that oneof the main routes of liposome passage through the skin is into thehair follicle."
Yarosh pointed out that liposomes come in two kinds, anionic andcationic. The former, he said, "are best for proteins, such as theenzymes which we specialize in delivering through the skin. Thecationic ones are better for DNA work."
Whether gene therapy for baldness, such as Hoffman envisages,succeeds, Yarosh pointed out, "would depend on the cause of thelack of hair growth. If there's a defective gene, then it's an excellentroute for delivery.
"But," he added, "most alopecia is probably not due to a geneticdefect in the hair follicle. A lot of it has to do with blood flow; thefollicles died because they were not being served properly."
Twenty years ago, Hoffman, as a National Academy of Sciencesexchange fellow, did research in Moscow's Institute of Bio-organicChemistry. He and a Russian collaborator, cell biologist LeonidMargolis, "invented the first DNA-entrapped liposomes."
Then, in the late 1980s and early 90s, Margolis visited Hoffman inSan Diego, where he had developed a way to culture skin."Margolis," Hoffman recalled, "put some liposomes with fluorescentdyes on these cultures. We had a confocal microscope, and we sawthe follicles light up."
He continued, "It dawned on us: we were delivering some thingsselectively to follicles. So then we started with melanin, then genes,and now we've graduated to mice."
-- David N. Leff Science Editor
(c) 1997 American Health Consultants. All rights reserved.