In the Chinatowns of Boston, New York, San Francisco, Los Angelesand other large cities, the commonest remedy sold is the bitter melon(Momordica charantia). "This fruit has been used in China andsoutheast Asia for centuries," said molecular biologist Sylvia Lee-Huang, "as an anti-infection and anti-tumor agent, and also as animmunomodulator. It's very widely eaten in the Chinese communityfor health reasons."
Another American community, that of AIDS-positive patients, hastaken up Chinese bitter melon for its anti-HIV properties, Lee-Huangsaid. The Bitter Melon Therapy Group, based in Los Angeles, shesaid, has been organizing tests in AIDS patients, and claimingpromising results.
Lee-Huang is a professor of biochemistry at New York UniversitySchool of Medicine.
"Many of these AIDS patients," she told BioWorld Today, "are long-term survivors, and they take nothing but bitter-melon extract." Thatdietary product, she said, "obtained from the fruit's dietary variety, isgood, but our medicinal variety has higher concentrations of theMomordica anti-HIV protein."
She added, "That AIDS group keeps asking me for our pure,recombinant product, but I cannot give it to them for obvious safetyreasons."
M. charantia is one of four botanical folk remedies, from as manyancient cultures, that Lee-Huang has dissected at the molecularbiochemical level, to purify their active therapeutic principles. Theother three plants:
* Trichosanthes kirilowii, "has been used in China for many, manyyears," Lee-Huang said, "and is well-known for its therapeutic effectin ovarian cancer and trophoblastic tumor, as well as against viralinfection. In Chinese, its common name means literally `the powderfrom the flower from the Gods.'"
* Dianthus caryophyllus is better known as the carnation _ as inflorist shops. "Native American Indians," Lee-Huang went on, "havelong used the leaves of Dianthus as a sort of Band-Aid for treatingcuts or infections."
* Gelonium multiflorum "is widely used by various cultures in theworld. From its origin in the Himalaya mountains, where it's knownas the "heavenly fruit," it's now much-favored in Germany andSwitzerland, Lee-Huang observed, as a panacean beverage "to fightagainst certain tumors and viral infections." (See BioWorld Today,Dec. 9, 1994, p. 4.)
"My mother," Lee-Huang said, "is a Chinese physician, and at anearly age I was not only exposed to her traditional medicinal plants,but also to seeing many patients cured by this way. So," shecontinued, "I am between traditional and modern medicine, and studythe molecular basis of traditional medicines."
Her laboratory at NYU, she said, which is supported by the NationalInstitutes of Health, "focuses on rational development of antitumorand antiviral agents from natural products." That rational drugdesign, she points out, is the opposite of the random inefficientscreening that marks so much of current drug discovery.
She started her research from these plants, isolated and purified eachof them to the homogeneity of a single compound, which has thedesired antitumor, antiviral activity, then cloned those proteins.
"So now we don't have to try so hard to go to the Himalayas to getthe seeds, or to China to get the bitter melons," Lee-Huang observed."We can use recombinant technology to produce them in our labs inlarge amounts. And our recombinant proteins are as active as thenatural protein."
She and her colleagues found out that these plant-derived compoundsare multifunctional, with at least three different activities:
* They inhibit HIV-1 integrase activity, which, she pointed out, "isvery important. If you don't integrate the viral genome in the hostgenome, you don't get replicative viral production or infection. Thisstep inhibits that integration."
* They also inhibit the topological activity of the HIV's LTR (longterminal repeat). The compounds unwind the viral DNA's supercoil,but then freeze it into a topologically inactive form. That is, it cannotrewind again. Many tumor drugs have the same activity."
* Third, "They inhibit protein synthesis in the cells, the ribosomalfunction. So usually the virus develops a resistance to many drugs,and mutates to get around them. This way, the virus has to mutate atdifferent regions in order to overcome the compound'smultifunctional properties."
Now topping Lee-Huang's research and development agenda is aseries of animal studies of the recombinant drugs. In collaborationwith National Cancer Institute scientists Hsiang-fu Kung and WilliamMurphy, she found that Momordica and Gelonium compounds "havepotent antitumor activity in SCID mice, against drug-resistant breasttumors.
And at the University of Washington's primate center in Seattle,veterinary virologist Che-chung Tsai determined that these twocompounds are as effective in simian immunodeficiency virus (SIV)as they are in HIV.
All four recombinant proteins are protected by U.S. and worldwidepatents, of which the most recent, U.S. No. 5,532,214, issued July 2,1996, covers a 29-kiloDalton (kDa) protein purified from the roottuber of Trichosanthes kiriloii, or produced by recombinant-DNAtechnology.
U.S. patent No. 5,484,889, dated Jan. 16, 1996, protects a 30 kDaprotein purified from Momordica charantia fruit or seeds, orrecombinantly synthesized.
U.S. patent No. 5,317,009, issued May 31, 1994, covers bothDianthus caryophyllus and Gelonium multiflorum extracts, naturaland recombinant.
"Our next objective," Lee-Huang said, "is to bring these from basicstudies in the lab to clinical situations. We're ready to proceed, andwould like to have some aggressive companies as R&D partnersunder these licenses."
All of the above patents, on which Lee-Huang is first inventor, claimanti-HIV and antitumor therapeutic utility. All are jointly held byNew York University and NIH.
Editor's note: An announcement recently submitted to the FederalRegister offers these patents to industry. for licensing andcommercialization. To obtain licensing information, contact ElaineGese, NIH Office of Technology Transfer, (301) 496-7056 ext. 282.For technical data, Sylvia Lee-Huang, NYU, (212) 262-5135. n
-- David N. Leff Science Editor
(c) 1997 American Health Consultants. All rights reserved.