Enzyme yields clue for aids treatments
Research team uncovers trigger that impedes work of body's natural
immune defense system
UBC researchers have discovered an enzyme that increases the rate
of human immunodeficiency virus (HIV) infection of cells -- a finding
that may lead to new AIDS therapies.
Faculty of Dentistry Prof. Christopher Overall and an interdisciplinary
research team discovered that the enzyme gelatinase cuts in two
the protein called Stromal Cell-Derived Factor (SDF) that normally
works to slow the AIDS virus by binding to cells.
"SDF is like a traffic signal. It has many roles in the body such
as directing certain white blood cells such as stem cells to stay
in bone marrow," says Overall.
The HIV virus stimulates cells to produce gelatinase in excessive
amounts, a process that Overall describes as "making an end-run
around one of the body's natural roadblocks to infection."
"We're now trying to determine if drugs that block gelatinase can
be used to boost treatments such as protease inhibitor cocktails
to slow the progression of AIDS," he says.
In the mid-1990's, scientists discovered that the cell receptor
that the AIDS virus uses to adhere to cells was a protein. This
is a good example of how viruses can hijack normal body proteins
to cause disease, says Overall.
Several anti-gelatinase drugs that tested relatively unsuccessfully
as a cancer therapy may now have potential in treating AIDS, he
Overall, a Canada Research Chair in Metalloproteinase Biology,
says that considerable further work is needed to determine if such
drugs can be effective and safe in treating AIDS patients.
"The exciting part of this discovery is that now we know that
the body can be triggered to remove normal protective effects of
SDF under certain circumstances," says Overall. "Now we can target
these triggers as a possible avenue of treatment."
The discovery was reported last month in the Journal of Biological
Chemistry. It builds on the work of research team member UBC
Biochemistry Prof. Ian Clark-Lewis who reported in 1996 that synthetic
variants of SDF lost their HIV-blocking ability.
Other team members include Prof. Chris Power of the University
of Calgary and UBC alumnus Angus McQuibban who was part of a similar
research project Overall led last year.
It found that gelatinase cut a similar protein called MCP-3 to
help block inflammation such as arthritis. The widely publicized
work led to several patents.