JCI online early table of contents: November 1, 2011

November 01, 2011

EDITOR'S PICK: Possible therapy for one form of inherited nerve dysfunction

Hereditary neuropathies are common nervous system conditions characterized by progressive loss of muscle control and/or sensory function. There are no effective treatments. However, work in mice, by a team of researchers led by Florian Eichler, at Massachusetts General Hospital and Harvard Medical School, Boston, has revealed a rational candidate oral therapy for one hereditary neuropathy -- hereditary sensory and autonomic neuropathy type 1 (HSAN1).

HSAN1 is thought to be caused by the accumulation of molecules known as deoxysphingolipids, which are toxic for cultured sensory neurons. Eichler and colleagues found that oral administration of L-serine to mice with a disease that models HSAN1 reversed the accumulation of deoxysphingolipids and reduced the severity of neuropathy. As the accumulation of deoxysphingolipids in humans with HSAN1 was also reversed by oral administration of L-serine, these data provide a rationale for the authors suggestion that L-serine supplementation could provide a treatment option for HSAN1.

In an accompanying commentary, Steven Scherer, at the University of Pennsylvania, Philadelphia, agrees with Eichler and colleagues that a clinical trial of L-serine as a treatment for HSAN1 should be done but he cautions patients to remember that the approach has not yet been proven to be effective.

TITLE: Oral L-serine supplementation reduces production of neurotoxic deoxysphingolipids in mice and humans with hereditary sensory autonomic neuropathy type 1

Florian S. Eichler
Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Phone: 617-724-7121; Fax: 617-643-6374; E-mail:

View this article at: http://www.jci.org/articles/view/57549?key=2bc381dd8e09d15886c4

TITLE: The debut of a rational treatment for an inherited neuropathy?

Steven S. Scherer
The Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Phone: 215-573-3198; Fax: 215-573-4454; E-mail:

View this article at:

EDITOR'S PICK: Potential treatment for iron overload disorders

Multiple organs, including the liver and the heart, become damaged if an individual has an excessive amount of iron in their body. Treatments for iron overload are arduous and/or have severe side effects. A team of researchers led by Elizabeta Nemeth, at the University of California, Los Angeles, has now generated data in mice that suggest that they have designed a promising new approach to reducing iron overload.

Iron overload is a hallmark of the genetic disease hereditary hemochromatosis and a major complication of beta-thalassemia -- an inherited blood disorder that results in chronic anemia. In both of these cases, low levels of the protein hepcidin cause the iron overload. Nemeth and colleagues have designed hepcidin agonists, which they call minihepcidins, that mimic the ability of natural hepcidin to lower levels of iron in the blood of mice. They therefore suggest that minihepcidins may be a useful new approach for treating individuals with iron overload disorders.

TITLE: Minihepcidins are rationally designed small peptides that mimic hepcidin activity in mice and may be useful for the treatment of iron overload

Elizabeta Nemeth
David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California, USA.
Phone: 310-825-7499; Fax: 310-206-8766; E-mail:

View this article at:

IMMUNOLOGY: Stopping autoimmunity in the NIK of time

Immune cells known as T cells play a key role in ridding the body of dangerous microbes. However, if they are not kept under control properly they can attack the body's own tissues and cells and cause autoimmunity. Working in mice, a team of researchers led by Susan Murray, at Oregon Health and Science University, Portland, has gained new understanding of the molecular mechanisms responsible for keeping T cells under control and preventing autoimmunity. Specifically, Murray and colleagues defined a T cell-intrinsic role for the protein NIK during immune responses and determined that dysregulation of this led to a rapid and fatal autoimmunity. They went on to suggest that therapeutics designed to decrease NIK activity in T cells might ameliorate autoimmunity.

TITLE: NF-kappa-B-inducing kinase plays an essential T cell-intrinsic role in graft-versus-host disease and lethal autoimmunity in mice

Susan E. Murray
Oregon Health and Science University, Portland, Oregon, USA.
Phone: 503-494-1499; Fax: 503-494-6862; E-mail:

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IMMUNOLOGY: CX3CR1: a protein with guts

Crohn disease (CD) and ulcerative colitis (UC) are the two most common forms of inflammatory bowel disease, affecting approximately 1 million people in the US. It is thought that in individuals with CD and UC, the normally restrained immune system reactivity to bacteria that live naturally in the gut becomes excessive and uncontrolled. A team of researchers led by Timothy Denning, at Emory University, Atlanta, has now gained new insight into the molecular immune mechanisms that limit immune system reactivity to bacteria in the mouse gut. Specifically, Denning and colleagues determined that expression of the protein CX3CR1 on immune cells known as macrophages was important for restraining inflammation in the gut. They went on to define some of the cellular reasons for this and hope that further molecular mechanistic insight could provide new therapeutic targets for inflammatory bowel disease.

TITLE: CX3CR1 regulates intestinal macrophage homeostasis, bacterial translocation, and colitogenic Th17 responses in mice

Timothy L. Denning
Emory University School of Medicine, Atlanta, Georgia, USA.
Phone: 404-712-8893; Fax: 404-727-8538; E-mail address:

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