Subject: Lab Notes 
Date: Published: 1/29/92 (117 lines)
Source: Wall Street Journal. Copyright Dow Jones & Co. Inc.

    Lab Notes
    ----
    By Marilyn Chase

    Coaxing `Retired' Enzyme
    To Fight Cancer and AIDS
    THERE'S a biochemical traffic cop that enforces the normal
 growth and maturation of new cells and then retires when the
 cells are safely performing their assigned roles.
    Some researchers are trying to develop drugs that coax
 that traffic cop back out of retirement to take on biological
 outlaws such as viruses and oncogenes, which disrupt the
 genetic machinery of cells, leading to diseases such as
 cancer and AIDS.  
    The traffic cop is an enzyme known as ADPRT, which seeks
 out abnormal genes and martials from six to eight other
 enzymes to cut up and destroy the defective or
 disease-causing genes.
    Ernest Kun, formerly a professor at the University of
 Californa at San Francisco, is leading a five-person team
 researching ADPRT at closely held Octamer of San Francisco.
 Octamer is developing five potential drugs that bind with
 ADPRT and reactivate it as a regulator of cellular law and
 order.  The targets, he believes, might be as diverse as
 B-cell leukemia, herpes and HIV, which causes AIDS.  
    In test-tube studies performed with William Rice of Emory
 University on the bone-marrow cells of leukemic children, the
 cancer cells were destroyed, but about two-thirds of the
 normal cells were spared, enough to regenerate the bone
 marrow after treatment, Dr. Kun contends.
    In AIDS, Dr. Kun reasons, ADPRT-based drugs might
 selectively target and clean out viral infection in cells
 without killing the cells themselves.  It's a hypothesis he
 hopes to prove in a forthcoming study with Fred Valentine of
 New York University and the Emory group.
    His goal is to develop drugs with the potential not only
 to inhibit but to wipe out viruses.
    Tumor-Necrosis Factor
    Gets Another Chance
    TAMING a promising but unruly drug may be possible, a
 Genentech team believes.
    The drug, tumor-necrosis factor, is a schizophrenic
 substance.  It's a natural human protein with potential
 virtues as an anticancer and antiviral agent, but it has a
 darker side that provokes inflammation, shock and cachexia,
 the wasting syndrome that causes cancer patients to lose
 drastic amounts of weight.  Such side effects have frustrated
 efforts to use it as a practical treatment.
    Genentech's David Goeddel and Louis Tartaglia have moved a
 step closer to mastering TNF's contradictory nature,
 according to their recent report in the Proceedings of the
 National Academy of Sciences.  The scientists say their mouse
 studies indicate the protein binds to two different receptors
 on human cells.  This, in turn, triggers distinct responses by
 cells -- such as immune-cell or killer-cell activity.  The
 finding raises the likelihood that scientists can design
 customized drugs against cancer, harnessing specific powers
 of TNF without inviting other, toxic reactions.
    "Because TNF causes so many physiological responses, it
 has been difficult to figure out how to use it to obtain
 specific therapeutic benefits in the absence of unwanted side
 effects," according to Genentech's Dr. Goeddel.  "Now that we
 know the two receptors have different functions, we can
 theoretically design a molecule that would bind to only one
 of the TNF receptors and {elicit} only the desired response."
    Designing an Oral Drug
    To Keep Anemia at Bay
    ANEMIA, a shortage of oxygen-carrying red cells in the
 blood, is currently treated with blood transfusions or
 intravenous infusions of erythropoietin, which stimulates
 production of red blood cells.
    EPO, pioneered by Amgen, is fine for kidney dialysis
 patients and for other acutely ill patients for whom needles
 are a part of life.  But what about less severe forms of
 anemia, where IV treatments with blood or EPO are expensive
 and inconvenient?  
    Designing an oral anemia drug, which would mimic the
 actions of the big EPO molecule in a small, easily ingested
 form, is one goal of scientists at Arris Pharmaceutical, a
 closely held startup in South San Francisco headed by
 Genentech alumnus Michael J. Ross.
    Using advanced computer techniques to "map" the structure
 of EPO and potential anemia-fighting substances, Dr. Ross is
 narrowing his sights to smaller synthetic drug molecules that
 may perform the same function in an orally active form.
    In the U. S. alone, more than 2.6 million people suffer
 from varying types of anemia.  Many of those people aren't
 that sick and might be more likely to take an oral drug, Dr. 
 Ross says.  An oral drug might ease effects of chemotherapy,
 he says, or help patients facing surgery who need to boost
 their red blood count as a precaution against bleeding during
 the operation.
    "In these situations, an oral drug would be competitive,"
 he says.  "Anytime you can avoid giving an IV drug, history
 says the oral drug wins the race."
    Odds and Ends
    TIMING is everything, says William J. M. Hrushesky of the
 Veteran's Administration hopital in Albany, N. Y. He found
 that giving the anticancer drug interleukin-2 to mice just
 before they awoke increased their tumor-fighting power, while
 giving it to active animals actually favored tumor growth.  .
 .  .  The secret to Leonardo da Vinci's strange mirror-writing
 may lie in his lefthandedness.  Scientist Victor Smetacek, in
 a letter to Nature, says lefties who are forced to write with
 their right hand may retain a mysterious ability to produce
 the backward script with the left.  Their flow of thought may
 even find better expression this way, he theorizes, because
 it draws upon the creative centers of the right half of the
 brain.

[This article is made available here by Dow Jones Co. for the
 personal and non-commercial use of callers to this bbs, in the
 hope that it will be of some help to those who are suffering
 from the disease and others who are seeking to help them.]