NEWS: Two Genetic Discoveries In Lupus Reported

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Two Genetic Discoveries In Lupus Reported - Ideas With Broad

Therapeutic Implications First Funded By The Lupus Research Institute

14 Sep 2006

Major discoveries that shed new light on how two different genes

contribute to systemic lupus erythematosus (“lupus”) have been

announced. Building on work initially funded by the Lupus Research

Institute, the findings published in the prestigious journal,

Science, offer real hope for better understanding and treating this

complex disease that affects more than 1.5 million Americans.

In lupus, for reasons that scientists are just now figuring out, the

immune system turns on itself and produces antibodies that can attack

virtually any healthy organ or tissue, from the kidneys to the brain,

heart, lungs, skin, joints and blood. Current treatments for lupus

are highly toxic.

" Both of these [science] papers provide important insight into

genetic factors that can contribute to the development of lupus, and

therefore, potential new therapeutic targets, " said Ann Marshak-

Rothstein, PhD, professor of microbiology at Boston University School

of Medicine.

New Clues to What Makes a Person Prone to Lupus

Silvia Bolland, PhD, who received a grant from the Lupus Research

Institute in 2001, is the lead author of the Science study that for

the first time characterizes how having a gene called the 'Y-linked

autoimmune accelerator,' or Yaa, makes the body more susceptible to

lupus.

Specifically, she shows that Yaa is a duplicated copy of a gene that

makes an RNA receptor known as TLR7. In mice with the extra copy of

the TLR7 gene, cells produce twice as much of the RNA receptor, which

make the mice more sensitive to RNA-associated proteins and more

likely to mount a harmful autoimmune response to the body's own RNA.

" Bolland's findings show that one extra copy of the gene is enough to

predispose to severe autoimmunity-direct evidence that minor genetic

mutations, small differences in expression, are important, " said Mark

Shlomchik, M.D., Ph.D., professor of laboratory medicine and

immunobiology at Yale University School of Medicine and co-chair of

the Lupus Research Institute's Novel Research Task Force that selects

research projects to fund.

" This study provides new understanding of how this gene works and

insight into the genetic basis of lupus, in other words, why lupus

runs in families,” he pointed out. “It also highlights TLR7 as

another potential target for lupus therapies. "

Subsequent funding from the National Institutes of Health made it

possible for Bolland to expand on her original Lupus Research

Institute research, and she now conducts lupus research at the

National Institute of Allergy and Infectious Diseases.

New Explanation for Immune System Breakdown in Lupus

The Science paper of University of Texas Southwestern Medical Center

professor K. Wakeland, PhD, who also received a Lupus Research

Institute grant in 2001, shows that in lupus-prone mice, having a so-

called receptor gene - Ly108 - contributes to a breakdown in

controlling the white blood cells of the immune system that produce

antibodies, called B cells. This breakdown causes the B cells to go

haywire and start producing antibodies to elements of the mouse's own

body (such as DNA), thereby leading to many of the manifestations of

lupus.

“My initial funding from the Lupus Research Institute played a

pivotal role in making these findings possible,” said Wakeland. “With

that early funding we developed an antibody that was critical in

helping Dr. Chandra Mohan [M.D., Ph.D., and lead study author] and

the team determine the function of Ly108 in this study. Moving

forward, the antibody will continue to be a valuable tool for the

research community. "

“This is the crux of the Lupus Research Institute's mission,' noted

Lupus Research Institute President and CEO, Margaret Dowd. “To

identify, fund and champion scientists with new ideas so that they

can validate their hypotheses and establish the data needed to

advance novel concepts in lupus research.”

Role of the Lupus Research Institute

The Lupus Research Institute is the world's only first-tier novel

lupus research funding organization, bridging the chasm between

promising new ideas for curing, preventing and treating lupus and

next-tier sources of government and private research funding. It

provides grants to researchers with novel, out-of-the-box ideas for

addressing lupus.

The urgent need for new approaches for the disease, for which there

have been no major treatments approved in the last 40 years, led to

the Institute's creation in 2000. Founded and funded by lupus

patients and their families, and developed with the help of leading

lupus scientists, the Institute now backs the largest number of

privately funded scientific investigators in lupus nationwide, to

date supporting 56 lupus researchers with $16 million from generous

donors.

To learn more about lupus and the Lupus Research Institute, visit

http://www.lupusresearchinstitute.org.

http://www.medicalnewstoday.com/medicalnews.php?newsid=51836