FDA Advisory Committee Recommends Approval Of ACTEMRA(R) (tocilizumab) For The Treatment Of Rheumatoid Arthritis

Roche announced that the
Arthritis Advisory Committee of the U.S. Food and Drug Administration (FDA)
by a near unanimous (10-1) vote recommended approval of ACTEMRA(R)
(tocilizumab), a novel interleukin-6 (IL-6) receptor-inhibiting monoclonal
antibody, for reducing the signs and symptoms in adults with moderate to
severe rheumatoid arthritis (RA).

“The committee’s overwhelmingly positive recommendation brings ACTEMRA
one step closer to becoming available to patients who suffer from the
painful and debilitating symptoms associated with RA,” said Kenneth Bahrt,
M.D., Global Medical Director, Autoimmunity, Roche. “Based on the strength
of the data presented, and the positive recommendation by the committee, we
are hopeful that the FDA will approve ACTEMRA for the treatment of RA and
provide a new option to patients who are not achieving adequate symptom
relief with current therapies.”

The committee’s vote was made after Roche presented results from five
Phase III clinical trials. The clinical development program was designed to
evaluate the effects of ACTEMRA on signs and symptoms of RA, physical
function, progression of structural damage, and health-related quality of
life. Of these five studies, three trials were conducted in patients with
inadequate response to disease modifying anti-rheumatic drugs (DMARDs), one
trial was conducted in patients who failed anti-tumor necrosis factor (TNF)
therapy, and one monotherapy study comparing ACTEMRA to methotrexate, a
current standard of care, was also conducted. Results of these studies
demonstrated that treatment with ACTEMRA — alone or in combination with
methotrexate or other DMARDs — significantly reduced RA signs and
symptoms, regardless of previous therapy or disease severity, compared with
current DMARDs.

About ACTEMRA (tocilizumab)

ACTEMRA is the first humanized interleukin-6 (IL-6) receptor-inhibiting
monoclonal antibody. Studies suggest that reducing the activity of IL-6,
one of several key cytokines involved in the inflammatory process, may
reduce inflammation of the joints and relieve certain systemic effects of
RA. The extensive clinical development program conducted by Roche includes
five clinical studies and has enrolled more than 4,000 patients in 41
countries, including the United States. Five Phase III studies are
completed and have reported meeting their primary endpoints. The LITHE
trial evaluating ACTEMRA in RA is an ongoing two-year study and is expected
to report complete data evaluating the effects of ACTEMRA on the inhibition
of structural joint damage in 2009. ACTEMRA is awaiting approval in the
United States and Europe.

ACTEMRA is part of a co-development agreement with Chugai, a Japanese
company. In June 2005, ACTEMRA was launched by Chugai in Japan as a therapy
for Castleman’s disease; in April 2008, additional indications for
rheumatoid arthritis, juvenile idiopathic arthritis and systemic-onset
juvenile idiopathic arthritis were also approved in Japan.

The serious adverse events reported in ACTEMRA clinical trials include
serious infections, diverticular perforations, and hypersensitivity
reactions including anaphylaxis. The most common adverse events reported in
clinical trials were upper respiratory tract infection, nasopharyngitis,
headache and hypertension. Increases in liver function tests (ALT and AST)
were seen in some patients; these increases were generally mild and
reversible, with no hepatic injuries or any observed impact on liver
function. Laboratory changes, including increases in lipids (total
cholesterol, LDL, HDL, triglycerides) and decreases in neutrophils and
platelets, were seen in some patients without association with clinical
outcomes.

About IL-6

IL-6 is a common protein found in all joints in the body and is a
natural substance that can raise inflammation. Everyone has IL-6 in their
body, but people with RA may have too much. If approved, ACTEMRA will be
the first and only medication to specifically target IL-6 in patients with
RA.

About Rheumatoid Arthritis

Rheumatoid arthritis is a progressive, systemic autoimmune disease
characterized by inflammation of the membrane lining in the joints. This
inflammation causes a loss of joint shape and function, resulting in pain,
stiffness and swelling, ultimately leading to irreversible joint
destruction and disability. Characteristics of RA include redness,
swelling, pain and movement limitation around joints of the hands, feet,
elbows, knees and neck that leads to loss of function. In addition, the
systemic symptoms of RA include fatigue, decreased hemoglobin, osteoporosis
and may contribute to shortening life expectancy by affecting major organ
systems. After 10 years, less than 50 percent of patients can continue to
work or function normally on a daily basis. RA affects more than 21 million
people worldwide with approximately 1.3 million adults affected in the
United States.

About Roche

Hoffmann-La Roche Inc. (Roche), based in Nutley, N.J., is the U.S.
pharmaceuticals headquarters of the Roche Group, one of the world’s leading
research-oriented healthcare groups with core businesses in pharmaceuticals
and diagnostics. For more than 100 years in the U.S., Roche has been
committed to developing innovative products and services that address
prevention, diagnosis and treatment of diseases, thus enhancing people’s
health and quality of life. An employer of choice, in 2007 Roche was named
Top Company of the Year by Med Ad News, one of the Top 20 Employers
(Science) and ranked the No. 1 Company to Sell For (Selling Power). In
previous years, Roche has been named as a Top Company for Older Workers
(AARP) and one of the Best Companies to Work For in America (Fortune). For
additional information about the U.S. pharmaceuticals business, visit our
website: rocheusa. Product and treatment information for
U.S. healthcare professionals is available at RocheExchange.

All trademarks used or mentioned in this release are protected by law

Roche
roche

View drug information on Actemra.

AZ-TMJ – Treating Obstructive Sleep Apnea May Improve Snoring In Many Patients

AZ-TMJ is once again leading the way in innovative and effective treatments for patients with obstructive sleep apnea (OSA). Approximately one in five adults have at least mild sleep apnea, and one in 15 are classified as moderate sleep apnea sufferers. Sleep apnea is a disorder where a person’s ability to breathe is impaired, resulting in a restless sleep and oftentimes snoring.

“It’s important for patients to understand the difference between snoring and OSA,” explained Dr. Stan Farrell. “Often the two conditions are related but are not directly correlated in all cases. Unlike simple snoring, OSA can be potentially life-threatening, requiring medical attention.” Dr. Farrell has developed an intraoral appliance that may be an alternative for patients not wanting to undergo surgery or wanting to avoid the use of a Positive Airway Pressure unit, also known as a CPAP.

Intraoral devices enlarge the pharynx, allowing a significant improvement in snoring if patients are appropriately pre-screened with regard to their individual anatomy. Close collaboration with an orofacial pain clinician, who has training in treating snoring and sleep apnea, is recommended for indication, adjustment and follow-up with an intraoral device.

After a thorough exam, AZ-TMJ can determine if an intraoral device is right for you. This device can be used with a Positive Airway Pressure unit (CPAP) to improve performance. Dr. Farrell has extensive training in Sleep Medicine and has successfully provided many patients with custom oral appliances that not only treated their sleep apnea, but often eliminated their snoring altogether.

Source:

AZ-TMJ

Autism Risk Higher In People With Gene Variant

Scientists have found a variation in a gene that may raise the risk of developing autism, especially when the variant is inherited from mothers rather than fathers. The research was funded by the National Institute of Mental Health (NIMH), part of the National Institutes of Health.

Inheriting the gene variant does not mean that a child will inevitably develop autism. It means that a child may be more vulnerable to developing the disease than are children without the variation.

The gene, CNTNAP2, makes a protein that enables brain cells to communicate with each other through chemical signals and appears to play a role in brain cell development. Previous studies have implicated the gene in autism, and in this study researchers were able to link a specific variation in its structure to the disease.

Results of the study were reported online January 10 in the American Journal of Human Genetics, by Aravinda Chakravarti, Ph.D., Dan E. Arking, Ph.D., and colleagues from the Johns Hopkins University School of Medicine, with Edwin Cook, M.D., and colleagues from the University of Illinois at Chicago.

“Autism is highly heritable. Identifying the genes involved is crucial to our ability to map out the pathology of this isolating and sometimes terribly disabling disease, which currently has no cure,” said NIMH Director Thomas R. Insel, M.D.

Autism is a developmental brain disorder that impairs basic behaviors needed for social interactions, such as eye contact and speech, and includes other symptoms, such as repetitive, obsessive behaviors. The symptoms sometimes cause profound disability, and they persist throughout life. Treatments may relieve some symptoms, but no treatment is fully effective in treating the core social deficits.

Although the cause of autism is not yet clear, studies of twins have shown that genes play a major role. It is likely that variations in many genes, influenced by environmental factors, interact during brain development to cause vulnerability to the disease. These genes have yet to be identified. Several candidates, including CNTNAP2, have been suggested.

The assertion that the CNTNAP2 gene appears to be involved is strengthened by the fact that each of the different analytical approaches the researchers used in this study led to the same conclusion. Results were replicated in a second, larger group of participants, further implicating the gene. Together, the two groups of participants comprised one of the largest autism studies reported to date.

The first part of the study included 145 children with autism and their parents, families that had two or more children with autism. Using a technique called genome-wide linkage analysis, the researchers found that a chromosome, 7q35, appeared to be linked to the disease.

Looking deeper into that chromosome, they identified a gene – CNTNAP2 – that contained a variant relevant to autism. Where a single segment of the genetic code could contain either the chemical base adenine or thymine, children with autism tended to have inherited the thymine variant.

To validate these findings, the researchers studied a separate group of participants; 1,295 children with autism and their healthy parents. The scientists again found that children with autism had higher rates of the thymine variant in the CNTNAP2 gene than would be expected to occur by chance.

When the researchers combined the data from the studies, they found that children with autism were about 20percent more likely to have inherited the thymine variant from their mothers than from their fathers.

“This is a common variant. People inherit it all the time. Our finding that it’s associated with autism more often when it’s inherited from mothers is intriguing, but needs to replicated,” Chakravarti said.

The role of CNTNAP2 in brain-cell development suggested by earlier studies has to do with differentiation, the process by which precursor cells develop into the different kinds of cells of the body. CNTNAP2 carries the genetic code for a protein, part of a family called neurexins, that appears to enable the precursor cells to develop myelinated axons. These are projections through which brain cells send each other electrical impulses essential for normal brain function at especially high speeds.

“CNTNAP2 is an excellent candidate gene for autism,” Chakravarti said. “It encodes a protein that’s known to mediate interactions between brain cells and that appears to enable a crucial aspect of brain-cell development. A gene variant that altered either of these activities could have significant impact.”

For more information about autism, visit the NIMH website here.

More information about autism also is available from the Department of Health and Human Services (DHHS) website at hhs/autism/.

The National Institute of Mental Health (NIMH) mission is to reduce the burden of mental and behavioral disorders through research on mind, brain, and behavior. More information is available at the NIMH website: nimh.nih/.

The National Institutes of Health (NIH) – The Nation’s Medical Research Agency – includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit nih.

Reference:

Arking DE, Cutler DJ, Brune CW, Teslovich TM, West K, Ikeda M, Rea A, Guy M, Lin S, Cook Jr. EH, Chakravarti A. A common Genetic Variant in the Neurexin-Superfamily Member CNTNAP2 Increases Familial Risk of Autism. American Journal of Human Genetics, online ahead of print, January 10, 2008.

National Institutes of Health

Monkey Studies Important For Brain Science

Studies with non-human primates have made major contributions to our understanding of the brain and will continue to be an important, if small, part of neuroscience research, according to a recent review published in the British medical journal, The Lancet.

Authors John P. Capitanio, professor of psychology at UC Davis and associate director of the California National Primate Research Center, and Professor Marina E. Emborg at the University of Wisconsin-Madison and the Wisconsin National Primate Research Center describe the importance of non-human primates in studies of Alzheimer’s disease, Parkinson’s disease, neurological complications of AIDS and stress.

“The key contribution of these studies is based on the similarities between the brains of humans and those of non-human primates,” said Capitanio, who studies animal behavior. Human and monkey brains show similar organization and structure, and the animals show complex behavior that can be compared to human behavior. However, he said, several complicating factors will always limit the number of animals used, including the financial expense, ethical issues and the relative difficulty of breeding compared to other model animals such as rodents.

All animal models have their strengths and limitations, Capitanio said. But just as a model building helps engineers and architects understand how a structure will work, animal models can help researchers understand body systems.

For example, the drug MPTP — first synthesized in an illegal drug laboratory — causes symptoms similar to Parkinson’s disease in both humans and monkeys, but not in rats or mice, which lack a crucial enzyme. Researchers are now studying monkeys treated with MPTP to better understand new treatments for Parkinson’s disease — the second most common neurodegenerative disease in people over 65.

“A model is not the real thing, but it can help you understand the real thing,” Capitanio said.

The California National Primate Research Center (CNPRC) is part of a network of eight national primate research centers sponsored by the National Center for Research Resources, a division of the National Institutes of Health.

Source: Andy Fell

University of California – Davis

Millennium Under-5s Mortality Goal Seems Unattainable

The Millennium Development Goal 4 (MDG4) included a target for lowering mortality for kids under-5 globally – it seems that the international community is failing to deal with this problem fast enough, according to an article published in The Lancet, this week’s issue.

Professor Christopher Murray, Director, Institute for Health Metrics and Evaluation, University of Washington, Seattle, WA, USA, and team put together all available databases into a computer model to forecast child mortality till 2015 worldwide, including 172 countries.

The researchers found:

– 1980 Global under-5 mortality = 110 per 1,000
– 2005 Global under-5 mortality = 72 per 1,000

– 1980 Child deaths globally = 13.5 million
– 2005 Child deaths globally = 9.7 million

– 1990 to 2015 Global under-5 mortality expected to fall by 27%
The MDG4 target was a 67% fall.

Areas of North Africa, the Middle East, southeast Asia and Latin America have had good rates of decline in under-5 mortality. However, other areas, such as sub-Saharan Africa, have had much slower declines, as well as persistently high fertility rates.

The authors say there should be better and timelier infant-mortality measurement through more fully using existing information and applying standard analytical strategies.

The authors write “We firmly believe that evidence on levels and trends in child mortality is a global public good and that the entire worldwide public-health community will benefit from more concerted efforts to enhance it.”

thelancet

:

Dutch-Funded $34.6M Sex Education Program Launched In Kenyan Secondary Schools

The Centre for the Study of Adolescence on Tuesday in Nairobi, Kenya, launched a two-year, 2.3 billion shilling, or about $34.6 million, sex education program for secondary school students funded by the Dutch government, Kenya’s Daily Nation reports. The initiative, called “The World Starts With Me,” initially will provide a computer program for students in 40 schools in Nairobi and Kenya’s Nyanza Province.

The computer program “aims at not only equipping the youth with computer skills, but the right information about HIV/AIDS, drug abuse, alcohol, pregnancy and sexually transmitted infections among others,” Rosemarie Muganda executive director of the adolescence center, said. She added, “It will also enhance the relationship between teachers and their students to ensure the high drop-out rate — especially among girls due to pregnancy — is minimized.”

Kees van Baak, the Netherlands’ deputy ambassador to Kenya, said the program would help girls in secondary schools abstain from sex and avoid having unplanned pregnancies. He added that the Kenyan government should “incorporate this new program in the school’s curriculum.” According to Kimeli Chepsiror, acting director of the National Council for Population and Development, studies have found that 23% of girls and women ages 15 to 18 in Kenya have children or are pregnant (Daily Nation, 7/11).

“Reprinted with permission from kaisernetwork. You can view the entire Kaiser Daily Health Policy Report, search the archives, or sign up for email delivery at kaisernetwork/dailyreports/healthpolicy. The Kaiser Daily Health Policy Report is published for kaisernetwork, a free service of The Henry J. Kaiser Family Foundation . © 2005 Advisory Board Company and Kaiser Family Foundation. All rights reserved.

UNICEF Executive Director Visits Cholera-impacted Residents At Haiti Treatment Centre

During a visit to the Haitian capital yesterday, Anthony Lake, UNICEF Executive Director, spoke with cholera patients and heard firsthand their concerns.

The visit took place at the GHESKIO Cholera Treatment Centre (CTC) in an impoverished area of the city. Lake also met with His Eminence Bishop Pierre-Andre Dumas, Coordinator of ‘Religion for Peace’ an organization that is mobilizing Catholics, Protestant, and Voodoo religious communities throughout Haiti to support cholera prevention and healthcare practices.

Lake’s visit to Port-au-Prince was made in support of the UN community’s response to cholera, and Haitians themselves in their actions against the disease. The cholera epidemic, which emerged just two months ago, continues to spread throughout Haiti. It is now claiming lives in all 10 administrative departments.

The centre, led by Dr. William Pape, is part of a network of 72 cholera treatment centres and units established across Haiti by UNICEF and partners. UNICEF is also carrying out cholera prevention activities such as supporting 5,000 schools, 300 child-friendly nutrition centres, and more than 700 residential care centres by distributing soap, water purification tablets, oral rehydration salts, and training teachers and children on safe hygiene practices.

Lake emphasized several points during his visit:

1. Pledging the support of the United Nations, NGOs, and UNICEF in Haiti’s fight against cholera;

2. The key to combating cholera is mobilizing influential communities such as religious groups and leaders;

3. The most important partners in defeating cholera are Haitians themselves, and helping them understand that cholera is preventable and treatable;

4. Cholera can affect anyone, and those who are sick should not be afraid to receive help at CTCs;

5. Current political tensions should not interfere with efforts to control cholera, a view no doubt supported by all parties;

6. All humanitarian organizations should be allowed to work and have unfettered access to medical supplies and their distribution.

The suffering now being experienced by children and their families in Haiti, suffering brought about by the January earthquake, floods, and the current cholera epidemic, demand continued local and international commitment as well as political will.

“As always, and without exception, children are the most adversely impacted by crises such as this cholera epidemic and the January earthquake,” said Lake. “The responsibility we all share is to ensure that children and families are protected from these emergencies as well as from the recent political tensions.”

He stressed that the current environment of uncertainty and insecurity in Haiti places children and families at even greater physical risk and also inhibits the efforts of humanitarian agencies such as UNICEF.

Source:

UNICEF

Bush During Meeting With British Prime Minister Brown Calls On G8 To Fulfill Aid Commitments To Africa

President Bush on Monday during a press conference in London with British Prime Minister Gordon Brown said that leaders from the Group of Eight industrialized nations should match aid commitments to Africa made by the U.S., the Kyodo/AOL News reports. Bush said that G8 leaders met last year and “discussed HIV and malaria in Africa, and they all came forth and said they would match the United States — except most nations haven’t matched the United States except for Great Britain.” He added that his “message to the G8″ during its summit in Japan next month is, “Looking forward to working with you, thanks for coming to the meeting, just remember that there are people needlessly dying on the continent of Africa today, and we expect you to be more than pledgemakers; we expect you to be check writers for humanitarian reasons.”

Brown at the press conference said that during the Japan summit, he will propose a plan, with the support of Bush, to recruit and train health workers for impoverished nations to prevent maternal deaths. Bush and Brown also said that they plan to call on G8 leaders to increase school enrollment in Africa (Kyodo/AOL News, 6/16).

Reprinted with kind permission from kaisernetwork. You can view the entire Kaiser Daily Health Policy Report, search the archives, or sign up for email delivery at kaisernetwork/dailyreports/healthpolicy. The Kaiser Daily Health Policy Report is published for kaisernetwork, a free service of The Henry J. Kaiser Family Foundation.

© 2008 Advisory Board Company and Kaiser Family Foundation. All rights reserved.

New Surgical Technique Repairs Arthritic Ankle Damage

News from the 2005 Annual Scientific Conference of the American College of Foot and Ankle Surgeons –

There’s good news for anyone with
painful arthritic ankles — a new surgical procedure imported from Europe is
showing encouraging results for relieving chronic arthritis pain without
taking away the overall movement and function of the joint.

The new ankle procedure was first reported in France and involves an
external-fixation procedure that applies tension to expand the joint and leave
room for new cartilage to form, thereby eliminating painful bone-on-bone
pressure, according to ACFAS President-elect James L. Thomas, DPM, FACFAS, a
foot and ankle surgeon practicing at the University of Alabama Birmingham.
“This is an exciting new approach for treating chronic ankle arthritis,” said
Thomas.

In an oral presentation at the American College of Foot and Ankle Surgeons
Annual Scientific Conference, Brad Lamm, DPM, AACFAS, a foot and ankle surgeon
affiliated with Sinai Hospital in Baltimore, reported that ankle-joint
distraction with external fixation for treatment of ankle arthritis is
starting to gain acceptance among foot and ankle surgeons in the US, although
its use has been limited.

“Most patients with ankle arthritis want to preserve a functioning joint
and are looking for alternatives to ankle-fusion procedures and joint
replacements to relieve their pain,” said Lamm. “While fusion surgery has
been a mainstay for many years and works very well for pain relief, fusing the
ankle joint makes it immobile and permanently stiff. Ankle joint distraction
with external fixation preserves the joint, eliminates pain and increases
function,” he explained.

Though new for treating ankle arthritis, minimally invasive, external-
fixation techniques are widely used by foot and ankle surgeons to repair
fractures. Bones are immobilized with pins, screws or wires, which are
secured outside the skin with clamps and rods that form an external frame.

For treating ankle arthritis, wires inserted through the skin are attached
to the frame, and the resulting tension pulls apart the ankle joint, creating
space for new cartilage to replace what was destroyed by arthritis. Prior to
applying the fixators, the foot and ankle surgeon may perform ankle
arthroscopy to clean out arthritic tissue and bone spurs.

Most external-fixation surgeries are performed in less than three hours
and the risk of infection is minimal. The patient can walk with the frame in
place the day after surgery and the fixators remain in place for about four
months until new cartilage is in place.

Thomas noted that even though the initial experiences with external
fixation for chronic ankle arthritis have been encouraging, more long-term
studies are needed before the procedure becomes a mainstream treatment for
these patients.

For further information about foot and ankle conditions and treatments and
to locate a foot and ankle surgeon in your area, contact ACFAS at
FootPhysicians.

The American College of Foot and Ankle Surgeons is the professional
organization for foot and ankle surgeons, doctors of podiatric medicine (DPM)
who are graduates of four-year podiatric medical colleges and have completed
surgical residencies. The organization is dedicated to developing surgical
standards for the care of the foot and ankle, sponsoring research, and
providing continuing education for its members.

American College of Foot and Ankle Surgeons
FootPhysicians

Discovery Of Small RNAs That Regulate Gene Expression And Protect The Genome

The list of short RNAs grows longer

RNA is best known as a working copy of the DNA sequence of genes. In this role, it’s a carrier of the genes’ instructions to the cell, which manufactures proteins according to information in the RNA molecule.

But molecular biologists have increasingly realized that many RNA snippets — so-called small RNAs — also directly influence which genes make proteins, and in some cases, how much protein. They’ve also found that some small RNAs play a unique role in protecting the integrity of genetic material.

Scientists at Cold Spring Harbor Laboratory (CSHL) have played a central role in these discoveries since the beginning of the decade. In recent weeks they have published additional findings adding to our knowledge of small RNAs, identifying a brand new class and clarifying how a known class acts to regulate gene activity.

“It turns out that there are more types of small RNA molecules than anyone initially suspected,” said Gregory J. Hannon, Ph.D., CSHL professor and pioneer in small RNA research. “And we are finding that each type that we discover acts in more ways than had previously been appreciated.”

Advanced Sequencing

RNA molecules consist of sequences of chemical units, or “bases,” that are copies of the DNA sequence. Each specific sequence can “recognize” related sequences in other RNA or DNA molecules. To regulate cellular activities, small RNA snippets, each containing 20 to 30 bases, join with special protein helpers to eliminate or modify target molecules. But of the billions of bases in a cell’s DNA, what determines which RNA snippets are chosen for this role”

Dr. Hannon and his collaborators are harnessing highly efficient new machines that determine the sequence of bases in millions of small RNA molecules simultaneously. They then scan the known genome to find matching sequences, as well as the sequences nearby. This original context is crucial to understanding why some snippets are chosen as regulators.

A New Class of RNA

Previously, researchers had recognized two classes of regulatory small RNA molecules in fruit flies, each with different protein partners. One class, called microRNAs, appears throughout the organism and acts to regulate the activity of many genes by joining with a special protein called Argonaute 1. A second class of RNA molecules, called piRNAs, occurs only in cells of the sex organs, and joins with different proteins, called Piwi proteins. Together, they act as a kind of immune system to suppress genetic interlopers called transposable elements, which were discovered at CSHL by Nobel laureate Barbara McClintock more than a half century ago, and which in certain cases can cause genomic havoc that underlies disease.

Dr. Hannon and his colleagues looked for RNA molecules that partner with a different protein, Argonaute 2, that belongs to the same family as Argonaute 1 and the Piwi proteins. Using advanced sequencing technology, they found that these small-RNA partners were distinct from either of the previously known classes of small RNAs. The new small-RNA class both modifies gene activity and suppresses transposable elements, thus serving as a defense mechanism.

These findings, the scientists write in a newly published paper in Nature, “expands the known repertoire” of small RNAs in fruit flies, and further blurs distinctions between the previously identified classes of small RNAs.

Pseudogenes: Not Just Junk

In related research, Hannon and his colleagues have published a paper announcing their discovery of a new source of regulatory RNA in mice. Many RNA sequences, such as microRNAs, are flagged as regulatory molecules because they physically fold on themselves. Special proteins recognize the resulting double-stranded RNA, and chemically slice it to release regulatory RNA snippets.

The CSHL team found that double-stranded structures also form from “pseudogenes.” Pseudogenes, in the past assumed to be useless “junk DNA,” are damaged copies of normal genes left over from previous genetic events. The researchers found that RNA copies of normal genes sometimes pair up with copies from the related pseudogenes, resulting in double-stranded RNAs that — far from being junk — are able to activate the cell’s regulatory apparatus.

The new findings add another layer of complexity to our understanding of the byzantine processes by which small RNA molecules influence genetic activity. “Viewed in combination,” Dr. Hannon and colleagues write, “our studies suggest an evolutionarily widespread adoption of double-stranded RNAs as regulatory molecules.”

“An endogenous small interfering RNA pathway in Drosophila” appeared in the advance online edition of Nature on May 7. The complete citation is: Benjamin Czech, Colin D. Malone1, Rui Zhou, Alexander Stark, Catherine Schlingeheyde, Monica Dus, Norbert Perrimon, Manolis Kellis, James A. Wohlschlegel, Ravi Sachidanandam, Gregory J. Hannon, and Julius Brennecke. The paper is available online at dx.doi/10.1038/nature07007.

“Pseudogene-derived small interfering RNAs regulate gene expression in mouse oocytes” appeared in the April 10, 2008 online edition of Nature. The complete citation is: Oliver H. Tam, Alexei A. Aravin, Paula Stein, Angelique Girard, Elizabeth P. Murchison, Sihem Cheloufi, Emily Hodges, Martin Anger, Ravi Sachidanandam, Richard M. Schultz, and Gregory J. Hannon. The paper is available online at dx.doi/10.1038/nature06904.

Cold Spring Harbor Laboratory is a private, nonprofit research and education institution dedicated to exploring molecular biology and genetics in order to advance the understanding and ability to diagnose and treat cancers, neurological diseases, and other causes of human suffering.

For more information, visit cshl/.

Source: Jim Bono

Cold Spring Harbor Laboratory