Previously Undetected
Immune System Cell
May Shed Light on IBM

Recent findings by researchers at Harvard Medical School, Brigham and Women’s Hospital, and Children’s Hospital, all in Boston, have identified a type of immune system cell previously unde-

Steven Greenberg tected in the biopsy samples of people with inclusion-body myositis (IBM).

MDA grantee Steven A. Greenberg at Harvard and Brigham and Women’s, and colleagues, who published their findings in the January issue of Muscle & Nerve, say the results suggest new hypotheses about IBM, as well as new potential treatment possibilities.

The cells, called dendritic cells, haven’t been previously reported in IBM muscle samples, because their identification requires looking at muscle specimens using specific markers, Greenberg says. Previous studies have used a more general type of marker and have misidentified many of the dendritic cells as T-cells, a better known immune system cell.

“Until the last decade, the study of dendritic cells has been relatively neglected in immunology and particularly in autoimmune disease,” Greenberg says, referring to diseases in which the body’s immune system mistakenly attacks its own tissue. Polymyositis (PM) and dermatomyo-sitis (DM), in which dendritic cells have previously been noted, have long been classified as autoimmune disorders. Experts have disagreed about how to classify IBM, although most believe the immune system is involved in some way.

“These [dendritic] cells are now recognized as central to the initiation and development of specific immune responses,” Greenberg says. One type, myeloid dendritic cells, is particularly abundant in IBM muscle tissue.

“Myeloid dendritic cells activate other immune system cells, particularly T-cells that are believed to be a major cause of muscle damage in IBM and polymyositis. Their presence in IBM and PM muscle provides a means by which these T-cells become

activated and attack muscle.”

Greenberg says new therapies for autoimmune diseases aimed at disrupting the function of dendritic cells and their interaction with T-cells could be considered for future trials in myositis, given these findings. He notes that two drugs — abatacept (Orencia) and efalizumab (Raptiva), both of which interfere with dendritic cell-T-cell interactions — are already approved by the Food and Drug Administration for other conditions.

FRG1 May Affect ‘Final
Version’ of Many Genes

Researchers at Leiden University in the Netherlands have added to existing knowledge about the FRG1 protein, which is made from a gene strongly implicated in facioscapulohumeral MD (FSHD) by some prominent investigators (see “Impossible Things,” page 28).

Silvana van Koningsbruggen and colleagues, including MDA-funded Silvere van der Maarel, say their experiments demonstrate the probable role of FRG1 in RNA splicing, a cellular process that takes “rough draft” genetic instructions to their final version.

Their paper, published online Nov. 14 in Chromosoma, reports identification of several splicing-related proteins associated with FRG1.

George Karpati Honored

Late last year, George Karpati, a world-renowned neuromuscular disease specialist and a longtime MDA grantee at the Montreal Neurological Institute (MNI), received the Prix du Quebec Wilder Penfield (Quebec Wilder Penfield Prize) and a special merit award from the Muscular Dystrophy Association of Canada. (Wilder Penfield, a pioneer in brain surgery who died in 1976, founded MNI in 1934.)

Karpati’s MDA-funded work has centered around strategies to transfer therapeutic cells and genes in Duchenne muscular dystrophy (DMD) and to increase production of the protein utrophin, which can partially compensate for the loss of the dystrophin protein that characterizes DMD.

He’s authored
some 250 origi-
nal research
papers and arti-
cles and, since
2002, has edited _{George Karpati}
or co-authored
five major books
on neuromuscular disease.
Karpati has received many addi-
tional accolades, including being
knighted by the Ordre National du
Quebec in 2005.

Are Blood Vessels Involved in FSHD?

Aresearch group that included Charles Thornton and Rabi Tawil, MDA clinic co-directors at the University of Rochester (N. Y.) Medical Center, have found evidence that blood vessel abnormalities may be involved in facioscapulohumeral muscular dystrophy (FSHD).

When they analyzed gene activity in people with FSHD, myotonic dystrophy (MMD) and no muscular dystrophy, they found that 44 genes were specifically overactive (upregulated) in early FSHD, and that 11 of these ( 32 percent) had a Researchers analyze gene activity using role in blood vessel structure or function. “gene chips” like this one (an Affymetrix

These findings may help explain why reti- ^{GeneChip) and computer software.} nal blood vessel abnormalities sometimes are part of FSHD. The researchers, who published their findings online Dec. 6 in Neurology, speculate that blood flow irregularities inside muscle fibers could also be a contributing factor in FSHD.