CAMBRIDGE, Mass. _ Predicting the age when Huntington's diseasesets in, protecting the gut lining from damage and delivering geneswithout viral vectors were three of the advances reported hereWednesday at the third annual Massachusetts Biotechnology Council(MBC) scientific symposium.Some 400 researchers, suppliers and academics attended the day-longevent, which updated the areas of human DNA sequences,"breakthrough medicines and immunology."With 149 companies, Massachusetts ranks as the second-largestbiotechnology location in the U.S., after the San Francisco Bay area's192.Interleukin-11 Restores Lesioned IntestinesLater this month in New Orleans, participants at the Digestive DiseaseWeek Meetings will hear about recombinant human interleukin-11(rhIL-11) as a protector of the intestinal tract. James Keith, a principalscientist at Genetics Institute, Inc. (GI), of this city, will describe anexperiment in which rats with acid-injured colons fared more thantwice as well after rhIL-11 treatment as did controls.A poster at the MBC symposium previewed that rat trial, in whichacetic-acid-induced colonic lesions simulated human inflammatorybowel disease. GI's chief operating officer, biophysicist Patrick Gage,told BioWorld Today that the finding broadens the company'stherapeutic uses for its rhIL-11. "It shows that this cytokine, in additionto its other properties, can potentially protect the mucosal membranesof the entire digestive tract _ from mouth to outlet."Far beyond bowel disease, the implications extend to potentiatingcancer treatment. Often the radiation and drugs used to fight tumorsmust be dose-limited or stopped, because of their destructive effects onthe gastrointestinal system. If rhIL-11 replicates in humans its gut-restoring effects in rodents, Gage suggested, it can greatly benefitcancer patients by permitting higher doses of tumor-ablatingchemotherapy and radiation.In monkey trials, also reported at the MBC symposium here, GI foundthat rhIL-11 increased blood platelet counts more than two-fold.,presumably by enhancing the size and maturation of bone marrowmegakaryocytes, which are platelet precursors.Interleukin-11 is a multi-functional cytokine, which regulates thegrowth and development of hematopoietic stem cells.Keith told BioWorld Today that GI discovered the cytokine'sgastrointestinal properties last year in joint research with BostonChildren's Hospital and Indiana University School of Medicine. Mostmice subjected to lethal combined doses of radiation and 5-fluouracil, awidely used cancer drug, died within 10 days. The cytotoxic agentsdamaged the villi lining their gut wall, letting infectious bacteria leakinto the bloodstream."Villus length recovered quickly in IL-11-treated mice, whileremaining abnormal in surviving control mice through day 9," reportedBlood for Jan. 1, 1994.Transkaryotic Plans Non-Viral Human TrialsBefore the end of 1994, Transkaryotic Therapies Inc. (TKT) of this cityexpects to start Phase I clinical trials of a patient's own human skinfibroblast cells transformed to synthesize human growth hormone.TKT's vice president of research, Douglas Treco, told BioWorld Todaythat the non-viral gene therapy, for which the firm has already filedinvestigational new drug applications with the FDA, will aim atcorrecting the body-wasting cachexia of cancer, and short stature inchildren.He described to the MBC audience TKT's game plan to treat chronicdiseases with somatic gene therapy based on delivering DNAsequences by electroporation or microinjection, rather than by viralvectors.Also nearing the clinic, interleukin-2 to treat renal cell carcinoma hasbeen approved in Europe, and human trials are pending there in 1994,TKT's founder-president and chief scientific officer, Richard Selden,told BioWorld Today.Hypercholesterolemia (the LDL gene), diabetes (insulin) andosteoporosis (calcitonin) and hemophilia (Factor IX or VIII) are all inactive preclinical development, as is erythropoietin (EPO), to treatsevere anemia. TKT scientists transformed mice to synthesize EPO atvarious levels, and have boosted their normal 45 to 50 percenthematocrit to 60 percent or higher, Treco said.The company has already constructed an initial Good ManufacturingPractice production facility in Cambridge, but looks eventually towardsatellite sites elsewhere, as its ex vivo approach to gene therapy spreadsinto medical practice."Ours is a new pharmaceutical paradigm," Treco said. "As opposed tomost pharmaceutical agents, except antibiotics, TKT's gene therapyhas the potential to cure a disease for the lifetime of a patient with asingle injection." He added, "Once a patient is implanted with his ownprotein-expressing cells, he will be medically monitored _ so thepharmaceutical companies will still have some way to market their testkits."`Junk' DNA Length Can Foretell Huntington's OnsetDavid Housman, a molecular geneticist at MIT, opened the humanDNA session by recalling that "Where the gene for Huntington'sdisease (HD) was, and how it worked, remained a mystery until lastyear."Then, after a decade-long search, molecular geneticists pinpointed theHD gene to human chromosome 4. They also determined that thenumber of apparently functionless repeats of the triplet codon CAG(cytosine-adenine-guanine) in its DNA sequence correlated with theseverity of the affliction. "Up to 39 repeats," Housman said, isrelatively symptomless, "but 40 and more, you're in trouble." (SeeBioWorld Today, June 1, 1993, p. 2.)Moreover, he revealed, the higher the number of these trinucleotiderepeats, the earlier the onset of HD. He cited a little girl two years old,with a repeat count of 90, who displayed the stigmata of HD usuallyexpected only in much older patients.Housman went on to lay out this grim timeline:Fourty-eight repeats go with symptoms at age 26; 50 at 25 years; 60 at14, and 70 at age 11."So now," he added soberly, for an individual at familial risk ofHuntington's, "we can say not only `if' but `when' _ a real timebomb." n

-- David N. Leff Science Editor

(c) 1997 American Health Consultants. All rights reserved.