EDITOR'S PICK: A treatment for one form of albinism?
Individuals with oculocutaneous albinism, type 1 (OCA1) have white hair, very pale skin, and light-colored irises because they have none, or very little, of the pigment melanin in their skin, hair, and eyes. Affected individuals have impaired eyesight and a substantially increased risk of skin cancer. Current treatment options are limited to attempts to correct eyesight and counseling to promote the use of sun protective measures. A team of researchers, led by Brian Brooks, at the National Eye Institute, Bethesda, has now generated data in mice that provide hope for a new treatment for a subset of patients with OCA1.
OCA1 is caused by mutations in the gene Tyr that result in either complete loss of activity of the protein tyrosinase (which is key to the generation of melanin) or the generation of a tyrosinase protein with reduced activity. Brooks and colleagues found that treating mice that model OCA1 caused by mutations that generate a tyrosinase protein with reduced activity (OCA-1B) with nitisinone, which is already FDA-approved for treating a blood condition known as hereditary tyrosinemia type 1, increases their eye and hair pigmentation. They therefore suggest that nitisinone could improve pigmentation in patients with OCA-1B and potentially ameliorate their vision loss.
In an accompanying commentary, Seth Orlow and Prashiela Manga, at New York University School of Medicine, New York, discuss the inspired study of Brooks and colleagues but caution that there are issues that might limit the use of nitisinone as a treatment for OCA-1B.
TITLE: Nitisinone improves eye and skin pigmentation defects in a mouse model of oculocutaneous albinism
AUTHOR CONTACT:
Brian P. Brooks
National Eye Institute, National Institutes of Health, Bethesda, Maryland, USA.
Phone: 301.451.2238; Fax: 301.402.1214; E-mail: brooksb@mail.nih.gov.
View this article at: http://www.jci.org/articles/view/59372?key=c430e731d09cdd050632
ACCOMPANYING COMMENTARY
TITLE: Informed reasoning: repositioning of nitisinone to treat oculocutaneous albinism
AUTHOR CONTACT:
Seth J. Orlow
New York University School of Medicine, New York, New York, USA.
Phone: 212.263.5245; Fax 212.263.5819; E-mail: Seth.Orlow@nyumc.org.
View this article at: http://www.jci.org/articles/view/59763?key=2743b2c01626971b0f13
EDITOR'S PICK: Could targeting a virus treat a common pediatric brain tumor?
Medulloblastomas are the most common cancerous (malignant) brain tumors in children. Although survival rates have improved over the years, medulloblastoma remains associated with substantial mortality, and long-term survivors often suffer debilitating effects from the intensive treatments. A team of researchers, led by Cecilia Söderberg-Nauclér and John Inge Johnsen, at the Karolinska Institutet, Sweden, has now identified a potential target for a more cancer-specific approach to treating medulloblastoma that they hope could improve patient outcome.
Söderberg-Nauclér, Johnsen, and colleagues found that a large proportion of primary medulloblastomas and medulloblastoma cell lines are infected with a virus known as human cytomegalovirus (HCMV). Furthermore, the majority of primary medulloblastomas expressed HCMV proteins. Importantly, the antiviral drug valganciclovir reduced human medulloblastoma tumor cell growth both in vitro and upon xenotransplantation in mice. Targeting a protein (COX-2) in the cancer cells, expression of which was found to be induced by the HCMV, had similar in vitro and in vivo effects. The authors therefore suggest that targeting HCMV and/or COX-2 could provide a new therapeutic approach to treating individuals with medulloblastoma.
In an accompanying commentary, Cynthia Hawkins and Sidney Croul, discuss in detail the concept that it could be possible to exploit the presence of HCMV to target medulloblastomas therapeutically. They also note that this approach might be applicable to other brain tumors, as several viruses have been linked to a range of brain tumors, including medulloblastomas, gliomas, and choroid plexus papillomas.
TITLE: Detection of human cytomegalovirus in medulloblastomas reveals a potential therapeutic target
AUTHOR CONTACT:
Cecilia Söderberg-Nauclér
Karolinska Institutet, Stockholm, Sweden.
Phone: 46851779896; Fax: 468313147; E-mail: cecilia.naucler@ki.se.
John Inge Johnsen
Karolinska Institutet, Stockholm, Sweden.
Phone: 46851772989; Fax: 48851773475; E-mail: John.Inge.Johnsen@ki.se.
View this article at: http://www.jci.org/articles/view/57147?key=5e97138a2931936d1eb7
ACCOMPANYING COMMENTARY
TITLE: Viruses and human brain tumors: cytomegalovirus enters the fray
AUTHOR CONTACT:
Cynthia Hawkins
The Hospital for Sick Children, Toronto, Canada.
Phone: 416.813.5938; Fax: 416.813.5974; E-mail: cynthia.hawkins@sickkids.ca.
View this article at: http://www.jci.org/articles/view/60005?key=816061e80dd99fedffa5
EDITOR'S PICK: Predicting prognosis in patients with inflammatory bowel disease
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. The severity of the symptoms and the frequency with which they recur varies widely among patients. Kenneth Smith and colleagues, at the University of Cambridge, United Kingdom, have now identified a gene expression profile that can divide patients with CD and UC into two otherwise undistinguishable subgroups — those with a high incidence of treatment-nonresponsive, frequently relapsing, or chronically active disease and those with mild disease. As discussed by the authors and, in an accompanying commentary, Laurence Turka, Simon Robson, and David Friedman, these data should allow physicians to identify those patients that require aggressive therapies such as potent immune system–suppressing drugs and prevent those that do not need such drugs from being exposed to their rare but potentially life-threatening side effects.
TITLE: Gene expression profiling of CD8+ T cells predicts prognosis in patients with Crohn disease and ulcerative colitis
AUTHOR CONTACT:
Kenneth G.C. Smith
University of Cambridge School of Clinical Medicine, Cambridge, United Kingdom.
Phone: 44.1223.336848; Fax: 44.1223.336846; E-mail: kgcs2@cam.ac.uk.
View this article at: http://www.jci.org/articles/view/59255?key=e497ac519765f9202fce
ACCOMPANYING COMMENTARY
TITLE: There's a goat behind door number 3: from Monty Hall to medicine
AUTHOR CONTACT:
Laurence A. Turka
Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA.
E-mail: lturka@bidmc.harvard.edu.
Simon C. Robson
Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA.
E-mail: srobson@bidmc.harvard.edu.
View this article at: http://www.jci.org/articles/view/60003?key=1ba64f03b4752af0b325
ENDOCRINOLOGY: Rare genetic disease yields insight into biology of cells affected in diabetes
Congenital hyperinsulinism of infancy (CHI) is a rare genetic disease characterized by dysregulation of beta-cells in the pancreas such that they secrete excessive amounts of the hormone insulin, which leads to very low levels of glucose (the fuel for cells in the body) in the blood. Studying the beta-cells from individuals with CHI not only teaches us about the mechanisms underlying this disease but can provide clues to the mechanisms underlying type 1 and type 2 diabetes, diseases that arise as a result of loss of function of the beta-cells. A team of researchers, led by Jean-Claude Henquin, at the University of Louvain, Belgium, has now analyzed in vitro, pancreatic tissue obtained from patients with CHI and generated data that cannot be explained by classic models of beta-cell function. As noted in an accompanying commentary by Benjamin Glaser, at Hadassah-Hebrew University Medical Center, Israel, the comprehensive work of Henquin and colleagues represents a 'milestone in beta-cell research'.
TITLE: In vitro insulin secretion by pancreatic tissue from infants with diazoxide-resistant congenital hyperinsulinism deviates from model predictions
AUTHOR CONTACT:
Jean-Claude Henquin
University of Louvain, Brussels, Belgium.
Phone: 32.2.7645529; Fax: 32.2.7645532; E-mail: jean-claude.henquin@uclouvain.be.
View this article at: http://www.jci.org/articles/view/58400?key=aa904a541cfb6cccf447
ACCOMPANYING COMMENTARY
TITLE: Lessons in human biology from a monogenic pancreatic beta–cell disease
AUTHOR CONTACT:
Benjamin Glaser
Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
Phone: 972.2.6776599; Fax: 972.2.6437940; E-mail: beng@cc.huji.ac.il.
View this article at: http://www.jci.org/articles/view/60002?key=383987e4717d91eb619d
CARDIOVASCULAR DISEASE: Linking independent risk factors for atherosclerosis
Atherosclerosis is a disease of the major arterial blood vessels that is one of the major causes of heart attack and stroke. High levels of cholesterol in the blood and elevated numbers of immune cells in the blood (a condition known as leukocytosis) are independent risk factors for atherosclerosis. A team of researchers, led by Andrew Murphy, at Columbia University, New York, has now defined in mice a mechanistic link between high levels of cholesterol in the blood, leukocytosis, and the development of atherosclerosis. The authors suggest that targeting the mechanistic link they uncovered could provide a new approach to preventing atherosclerosis. In an accompanying commentary, Christian Weber and Oliver Soehnlein, at Ludwig-Maximilians-University Munich, Germany, discuss in detail the therapeutic implications of the work of Murphy and colleagues.
TITLE: ApoE regulates hematopoietic stem cell proliferation, monocytosis, and monocyte accumulation in atherosclerotic lesions in mice
AUTHOR CONTACT:
Andrew J. Murphy
Columbia University, New York, New York, USA.
Phone: 212.305.5789; Fax: 212.305.5052; E-mail: am3440@columbia.edu.
View this article at: http://www.jci.org/articles/view/57559?key=b09574f6c14b84d4fb34
ACCOMPANYING COMMENTARY
TITLE: ApoE controls the interface linking lipids and inflammation in atherosclerosis
AUTHOR CONTACT:
Christian Weber
Ludwig-Maximilians-University Munich, Munich, Germany.
Phone: 49.0.89.5160.4350; Fax: 49.0.89.5160.4352; E-mail: christian.weber@med.uni-muenchen.de.
Oliver Soehnlein
Ludwig-Maximilians-University Munich, Munich, Germany.
Phone: 49.0.89.5160.4350; Fax: 49.0.89.5160.4352; E-mail: oliver.soehnlein@med.uni-muenchen.de.
View this article at: http://www.jci.org/articles/view/60457?key=ddbaf81a074c6939cb25
Journal
Journal of Clinical Investigation