UNICEF To Provide Support To Nearly One Million Children Affected By Earthquake In Chile

UNICEF will provide assistance to the estimated one million children and their families affected by the earthquake in Chile which struck on 27 February. It is unclear how much more damage the second quake today has caused, but the first quake followed by a tsunami caused widespread damage and over 500 deaths. Six regions, home to some 80 per cent of the population of Chile were affected by the quake. The government had declared these regions as “catastrophe zones”.

The worst affected areas are some of the poorest in the country. Roads have been cut off, and entire villages in the coastal zones were wiped out by the Tsunami. Government buildings, schools, health facilities and at least 500,000 homes have been destroyed or badly damaged.

“As in any disaster, children are the ones suffering most. They are particularly vulnerable to cold, hunger and outbreaks of disease. Their lives have been brutally disrupted and many of them will have difficulty coping with such an upheaval. We must help them now,” said Gary Stahl, UNICEF Representative in Chile.

UNICEF is asking for $3.5 million to meet the immediate and medium-term needs of children and women throughout the affected areas. Assistance will include psychosocial support, emergency education and water and sanitation. UNICEF is working closely with the new government of Chile which was sworn in today.


Tobacco Smoke Has Harmful Impact On Asthma, Rhinitis And Immunity

Tobacco smoke is involved in uncontrolled asthma, a diminished response to anti-asthma drugs, rhinitis, nasal obstruction, and deregulation of the immune system according to an international expert at the annual meeting of the American College of Allergy, Asthma and Immunology (ACAAI) in Miami Beach, Fla.

Tobacco smoking has been mainly associated with chronic obstructive pulmonary disease (COPD), and is attributed to being one of the main reasons that COPD disease is the fourth leading cause of death in the United States.

“Recent studies have shown that smoking can be linked with other respiratory diseases such as asthma exacerbations and rhinitis,” said Carlos Baena-Cagnani, M.D., faculty of medicine, at Catholic University of Cordoba in Argentina. “Both active and passive smoking has been shown to be involved in uncontrolled asthma and associated with asthma exacerbations in children and adolescents.”

According to Dr. Baena-Cagnani, active smoking also causes changes in inflammation in asthma patients, diminishes their response to anti-asthma drugs, and has been found to induce nasal obstruction and decreased mucociliary clearance.

“The message is that smoking is a risk factor for the inception of asthma in allergic rhinitis patients, and it should be discouraged in patients with rhinitis,” he said. “There is increasing and compelling evidence that respiratory diseases, such as asthma and COPD, are also related to a deregulation of the immune system, especially the innate (natural) immunity.”

According to the latest World Health Organization statistics, currently 300 million people have asthma, and 210 million people have COPD, while millions have allergic rhinitis and other often under-diagnosed chronic respiratory diseases, Dr. Baena-Cagnani said.

“The impact of tobacco smoking is huge, with over one billion people exposed to unhealthy air in which tobacco smoking plays a major role,” he said.

Current statistics show that approximately 20 percent of U.S. adults are smokers, and more than half of them have the desire to quit according to a “Smoking Cessation Toolbox for Allergists” recently published in Annals of Allergy, Asthma & Immunology, ACAAI’s scientific journal. Surveys indicate that a physician’s advice to quit is an important motivator to quit smoking. “Screening, providing brief counseling, and prescribing first-line smoking cessation medications will help the United States get closer to achieving the national goal laid out in Healthy People 2010 of smoking rates of 12 percent or less” the investigators report.

“Allergists are aware of the significant impact that tobacco addiction has on our patients, and we are committed to initiating and reinforcing smoking cessation as part of our treatment plan,” said Richard G. Gower, M.D., an allergist/immunologist at Marycliff Allergy Specialists in Spokane, Wash., and president of ACAAI.

“We play an important role in advocating for children exposed to harmful second-hand smoke. Removing smoking as an impact factor, especially for asthma patients, improves their response to therapy and results in healthier patients.”

An allergist, an expert in the diagnosis and treatment of allergies and asthma, can perform allergy testing to identify the specific substances that trigger allergic reactions and determine the most appropriate and effective treatment.

American College of Allergy, Asthma and Immunology (ACAAI)

Christmas Merriment Can Trigger Asthma – National Asthma Council Australia

The National Asthma Council Australia is warning the two million plus Aussies with asthma to approach Christmas with caution this year as the season’s many hidden asthma triggers could be enough to start you wheezing.

In fact, according to the Council, Christmas this year could be particularly problematic with the hay fever season lingering due to recent rains and a prolonged grass growing season and widespread thunderstorm activity, which can stir up pollen in the air, increasing its potency.

Even the humble Christmas tree – real and fake – can harbour hidden asthma triggers.

“Most people are unaware that Cypress and pine trees produce high amounts of pollen and pollen can trigger hay fever symptoms and asthma, especially when the trees are displayed indoors,” Kristine Whorlow, National Asthma Council Australia Chief Executive Officer said.

“Artificial trees may seem like a safe alternative, but these trees are often used year after year and they can accumulate dust and even mould in storage and both of these are common asthma triggers.”

To minimise the Christmas wheeze, the National Asthma Council Australia recommends vacuuming artificial trees and decorations as you get them out of the box, unpacking them outside if possible and wiping down artificial trees before putting them up inside.

Other potential triggers that are likely to be encountered during the festive season include dusty decorations, highly scented candles and extremes of emotions including stress and laughter.

“If you have asthma it’s important to be aware of your asthma triggers and avoid them if possible. You should also continue to follow the personal written asthma action plan that you have developed with your doctor,” Kristine Whorlow advised.

“At this time of the year, make sure you have your medication with you and take it as advised by your doctor, even if you are out partying or away on holidays.”

Christmas Asthma Triggers Include:

Christmas Trees

Natural Christmas trees may harbour pollen and artificial trees can be a major dust trap and may also accumulate mould – all three can trigger asthma in susceptible people.


Have the vacuum on hand when you unpack last year’s box of decorations. Ideally, unpack them outside and clean before use. If you are attached to your soft decorations, such as Christmas-themed soft toys or felt stockings, you can put them in the freezer overnight before use to kill dust mites.

Outdoor Parties

The office break up in the park or Christmas Day under the Aussie sun could spell trouble for some people as there is still a lot of pollen floating around, particularly on windy days, which can trigger asthma and hay fever.

Scented Candles

Scented candles have become one of the most popular Christmas gifts and atmospheric decorations. Unfortunately, for some people with asthma, the perfume in scented candles may trigger symptoms. It’s a good idea to check if anyone you’re giving such a gift to has their asthma symptoms triggered by odour, however pleasant.


Christmas is a time of many emotions. ‘Tis the season to be jolly, but it can also be the season for added pressures and stress as the year races to a close and that Christmas deadline looms. Stress and anxiety can be a trigger for asthma as can other intense emotions such as yelling, crying and laughing.


National Asthma Council Australia

Endogenous Stem Cells Activators, Inc. Announces The Availability Of KRONOS IV In The Treatment Of Alzheimer’s Disease

Endogenous Stem Cells Activators, Inc. is a new Nevada Corporation whose main asset is KRONOS IV.

KRONOS IV is a drug that activates the dormant stem cells in the brain of AD patients, and coaxes them through a process of neurogenesis, as evidenced by the presence of growth factors (GFs) into becoming active neurons.

These cells can repair or rebuild the hippocampus, an area of the brain where memory is located, that is severely damaged by the AD.

KRONOS IV is based upon a drug(s) presently available on the market that had been approved by the FDA for a different claim.

As such KRONOS IV would be available to the AD patients upon prescription by a physician, based upon the off-label regulations that allow physicians to prescribe drugs for medical conditions, other than the one approved by the FDA.

We have reasons to believe that KRONOS IV will be available before the end of the year, at a tentative price of $1200 a month, or a total of $7200 for six months treatment.

KRONOS IV in its initial phases had been used by 10-12 physicians in the US and France who reported impressive results in the areas of memory, attention, orientation, also in controlling incontinences, and most importantly in improving the Quality of Life (QoL) of the AD’s family members living under a continuous high stress.

First KRONOS results had been reported at the Second International Symposium on Stress, Monte Carlo, Monaco November 21st, 1979 honored by the participation of four Nobel Prize winners, Dr. Jonas Salk and top scientists from 10+ countries.

Subsequently a positive commentary about KRONOS presentation at the Symposium had been published in JAMA (Journal of American Medical Association), April 25th, 1980.

KRONOS IV is our response to the call for help, now, from the families of the 5.3 million patients with AD, who know well that in the next 4-5 years, few if any survivors would be around, plus another 5.3 MM new AD patients that would be entering the Alzheimer’s inferno, soon.

Dr. Alfred T. Sapse, the developer of KRONOS IV, is a veteran since 1962 in the field of AD and aging, first in his native country Romania, and in the US where he succeeded in introducing the Romanian anti-aging drug Gerovital H3, now used by tens of thousands. He has received two US patents on Alzheimer’s, and as President of Stem Cell Pharma, Inc., a Nevada corporation formed in 2005, he has developed a new technique of implanting stem cells from the amniotic membrane of the placenta, a technique used abroad in the treatment of medical conditions, including Alzheimer’s and aging.

Endogenous Stem Cells Activators, Inc.

Positive preliminary results from 2nd pivotal CDP870 Phase III Trial in rheumatoid arthritis

UCB Pharma today announces positive preliminary results from the second Phase III clinical trial with CDP-870 in rheumatoid arthritis (“Study 011″). CDP-870 was designed and developed by Celltech, which recently became part of UCB. Study 011 assessed the safety and efficacy of CDP-870 as monotherapy on signs and symptoms of disease over a six month period in patients who had active moderate to severe disease despite previous treatment with methotrexate and other disease modifying anti-rheumatic drugs (“DMARDs”).

This study met its primary endpoint, as assessed by the number of patients achieving a 20% reduction in the American College of Rheumatology score (“ACR20 response”) at 24 weeks. A significant ACR20 response was seen at week 1 in the study, the first time point, and was maintained for the duration of the study. Adverse events in Study 011 were consistent with those seen in previous studies with CDP-870.

Roch Doliveux, Chief Executive Officer of UCB Pharma, commented: “CDP-870 has now clearly demonstrated its safety and efficacy, since we obtained positive results in both monotherapy and combination therapy Phase III clinical trials in rheumatoid arthritis. Our focus going forward is on developing a more patient-friendly formulation and delivery system, as well as further enhancing the competitive profile of this very promising drug.”

Concurrently, UCB Pharma continues to progress rapidly the double-blinded Phase III trials with CDP-870 in Crohn’s disease for which enrolment will be completed by the end of the year.
CDP-870 is the first anti-TNF-alpha pegylated antibody fragment (FAb) for the treatment of rheumatoid arthritis and Crohn’s disease; this confers the molecule with unique properties in terms of affinity, selectivity and duration of action.

Full results will be released after conclusion of the entire RA Phase III programme.

UCB Pharma is part of the UCB Group of companies, a global pharmaceutical and specialty chemical company with headquarters in Brussels, Belgium. UCB Pharma is a leading biopharmaceutical company, specialising in the fields of central nervous system disorders, allergy and respiratory disease, immune and inflammatory disorders and oncology. UCB Pharma’s key products are Keppra® (antiepileptic), Xyzal® and Zyrtec® (antiallergics), Nootropil® (cerebral function regulator), and Tussionex® (antitussive). UCB Pharma employs over 8,000 people operating in over 100 countries, and in 2003 achieved sales of ?1.5 billion.


UCB – Press contacts
Laurence Battaille Tel.: +32 (2) 559 95 88
Head of Corporate Communication
Jon Coles Tel.: +44 (0)20 7404 5959
Wendel Carson Tel. :+44 (0)20 7404 5959

Asthma Inhalers To Change To Help The Environment, UK

One of the most commonly used forms of treatment for people with asthma is being replaced by an inhaler which is more environment friendly.

CFCs have been used in asthma inhalers for a long time and are safe to use for people with asthma. However they are gradually being phased out because of their damaging effect on the earth’s ozone layer.

The change will affect people with asthma who are currently using an aerosol preventer inhaler which contains CFCs (usually brown, beige or dark red). People with asthma with an aerosol reliever inhaler (usually blue) will not need to make any changes as these are already CFC-free.

The medicines in the CFC-free preventer inhaler work in the same way as the medicine in inhalers with CFCs. They are safe and just as effective as they continue to control the swelling and inflammation in the airways, stopping them from being so sensitive and reducing the risk of an asthma attack. Only the propellants used have changed.

Kate Jarvis, Health Promotion Manager for Asthma UK said: ‘If you use a CFC-containing preventer inhaler, you should continue to use it as prescribed until you have had a consultation with your doctor or asthma nurse and together you’ve agreed an alternative. Once you have decided which inhaler device is best for you, your doctor or asthma nurse should show you how to use and take care of your new inhaler. They should also provide you with an updated written personal asthma action plan to help you manage your asthma.

If you change to a CFC-free preventer inhaler it is important to ensure that you are happy with your new inhaler and how it is working for you. If you are not happy with your new inhaler for any reason, it is important that you go back to your doctor or asthma nurse to find the device and medicine that suits you best.’

Asthma UK has produced a factfile that lists all the affected preventer inhalers and their CFC-free alternatives. It also provides more general advice about the switch to CFC-free inhalers. These can be downloaded from our website at asthma/cfcfree


1. In accordance with the 1987 Montreal Protocol on Substances that Deplete the Ozone Layer, all products that contain chlorofluorocarbons (CFCs) are, where possible, being replaced with CFC-free alternatives.

2. Asthma UK is the charity dedicated to improving the health and well-being of the 5.2 million people in the UK whose lives are affected by asthma. For up-to-date news on asthma, information and publications, visit the Asthma UK website asthma

3. Asthma UK is the major funder of asthma research in the UK. Each year we spend approximately ??3 million on research which includes project grants, four fellows, and two professors.

4. For independent and confidential advice on asthma, call the Asthma UK Adviceline, which is staffed by asthma nurse specialists. It is open weekdays from 9am to 5pm on 08457 01 02 03. Or email an asthma nurse at asthma/adviceline


WFP Says Ethiopia Flooding Far From Over: 118,000 Affected

With heavy rains continuing to pound much of Ethiopia, the United Nations World Food Programme (WFP) said today that 118,000 people – with hundreds killed or missing – have been hit by devastating floods in the past month and warned that the numbers of displaced, homeless and severely affected could rise further.

Although floods are relatively common during the June to September rainy season in Ethiopia, this year the country has experienced some of the heaviest and most intense on record, with water levels rising to critical levels at three dams in the west, south and north, where local residents have been advised to leave.

WFP, together with other humanitarian partners, has provided 37.5 metric tons of grain, 1.1 ton of vegetable oil, 4 metric tons of pulses and 50 cartons of biscuits and supplementary food for distribution to those affected. The food assistance, together with non-food items, has already been dispatched to four locations where survivors are temporarily sheltered.

“Throughout the country, the government and humanitarian groups, including WFP, are racing against the clock to deliver supplies and assistance to the people who are suffering,” said Abnezer Ngowi, WFP Acting Country Director in Ethiopia. “This is a race which must be won because so many lives are at stake.”

“We have distributed food and assigned staff to nearly all the affected areas throughout the country and are supporting the government and our partners in coordination and relief efforts. The scale of this crisis is huge – the magnitude and impact remains to be seen,” said Ngowi.

The Omo River has already burst its banks and flooded large swathes of land in the south west, some 800 kilometres south of the capital, Addis Ababa.

Thousands of people are marooned and encircled by flood waters in isolated areas along the Omo River valley, following flooding which has killed more than 300 people and washed away almost 3,000 livestock. Earlier flash floods in Dire Dawa killed 254 people, and with many still missing, the national death toll may rise.

Since search and rescue efforts began in south Omo on 15 August, 1,300 people have been rescued, but lashing rain and devastated infrastructure have hampered relief efforts. National army personnel have been deployed to assist and boats and helicopters are on the scene, airlifting survivors and dropping food and clean water to those people they can reach.

Of mounting concern is also the situation in Amhara region, northern Ethiopia, where 20,000 people have apparently been affected by flood waters from Lake Tana. Some 10,000 of these are camped in temporary shelters.

The government has assembled a rapid assessment team, including a field monitor from the WFP office in Dessie, to establish the extent of the floods. The government has also allocated food, plastic sheeting and tents for immediate dispatch to the displaced.

In Dire Dawa, eastern Ethiopia, where 254 people died and many more are still missing, a joint UN, inter-agency and government flash appeal for US$5.82 million has been issued, covering a range of food and non-food items as well as provision for rehabilitating the infrastructure.

“Funds are urgently needed to allow aid organisations like WFP to undertake additional and much needed food, nutrition, health, sanitation, water, logistics and road interventions,” said Abnezer Ngowi. “We must concentrate on the massive humanitarian task ahead.”

American soldiers from a US military base in neighbouring Djibouti arrived in Dire Dawa at the weekend to assist the emergency services in the post-flood operations. The government has also appealed to the international community to provide urgent search and rescue assistance in the form of helicopters and motor boats.

With more rains predicted over the coming weeks, WFP has warned that the crisis is still far from over. The Ethiopian government and military have stepped up the evacuation of scores of people from flood-prone, low-lying areas to higher ground.

The government is also standing by to release some of the excess water already in the Koka Dam on the Awash River in the east, and in the Tise Aby Dam on the Blue Nile River, in northern Ethiopia. Flood waters are also spilling over from the Gilgel Gibe Dam on the Omo River.

WFP is the world’s largest humanitarian agency: each year, we give food to an average of 90 million poor people to meet their nutritional needs, including 58 million hungry children, in at least 80 of the world’s poorest countries.

For further information please go to:
World Food Program WFP – We Feed People

Hawai’i Department Of Health Cites Companies For Air Pollution Violations

The Hawai’i State Department of Health (DOH) Clean Air Branch has issued Notices of Violations and Orders against Goodfellow Brothers, Inc., Tesoro Hawai’i Corporation, Earthworks Pacific, Inc., and Meadow Gold Dairies, Inc., for air pollution violations.

The DOH Clean Air Branch issues air permits and conducts complaint investigations to minimize air pollution impacts on the public. Through the permit and complaint investigation process, the DOH ensures continuing compliance with applicable state and federal emission standards. In general, penalties are assessed on violators and any economic benefit they may have gained from their noncompliance.

The following companies were cited:

1. Goodfellow Brothers, Inc., for late submittal of its semi-annual report form for January through June 2007 as required by their permit. The violation was discovered on January 30, 2008 during a records review of the 780 TPH stone processing plant located at 480 C Welakahao Road, Kihei, Maui; a penalty of $2,400 has been paid for the violation.

2. Tesoro Hawai’i Corporation, for failing to perform a sulfur dioxide test, specifically a relative accuracy test audit for their sulfur recovery unit tail gas incinerator sulfur dioxide continuous emissions monitoring system in the third quarter of 2007. The violation was discovered during a records review on February 8, 2008 of the oil refinery located at 91-325 Komohana Street, Kapolei, Oahu; a penalty of $2,300 has been paid for the violation.

3. Earthworks Pacific, Inc., for not taking reasonable precautions to prevent visible fugitive dust from becoming airborne at the Kaua’i Marriott Resort and Beach Club construction site located at 3610 Rice Street, Lihue, Kaua’i. The fugitive dust violations occurred on February 29 and March 31, 2008 and a penalty of $6,500 has been imposed. The DOH and Earthworks Pacific, Inc. will be entering into a consent order in the near future.

4. Meadow Gold Dairies, Inc., for late submittal of its semi-annual report form for July through December 2007 as required by their permit. The violation was discovered on March 28, 2008 during a records review of the plant’s two 150 hp Cleaver-Brooks boilers located at 910 Sheridan Street, Honolulu, Oahu; a penalty of $2,400 has been paid for the violation.

Hawai’i State Department of Health

Aeolus Pharmaceuticals’ AEOL 10150 Protects Lungs From Fractionated Radiation; Reduces Angiogenesis And Inflammation

Aeolus Pharmaceuticals, Inc. (OTCBB: AOLS) reported data published in the peer-reviewed journal, Free Radical Research, show the Company’s lead compound, AEOL 10150, provided statistically significant protection of the lungs of Fisher 344 rats exposed to fractionated radiation in a study led by Zeljko Vujaskovic, M.D. Ph.D. of Duke University. The study also demonstrated that the compound reduced markers for tissue hypoxia, angiogenesis, inflammation and oxidative stress in rats studied in this experiment.

The primary objective of this study was to determine whether administration of AEOL 10150 reduces the severity of long-term lung injury induced by fractionated radiation. Fisher 344 rats were randomized into five groups: radiation therapy plus AEOL 10150 (2.5 mg/kg BID), AEOL 10150 (2.5mg/kg BID) alone, radiation therapy plus AEOL 10150 (5 mg/kg BID), AEOL 10150 (5 mg/kg BID) alone and radiation therapy alone. Animals received five 8 gray (“Gy”) fractions of radiation therapy to the right hemithorax each day for five days. AEOL 10150 was administered 15 minutes before radiation exposure and 8 hours later each of the five days of radiation therapy treatment, followed by subcutaneous injections for 30 days, twice daily. Lung histology at 26 weeks revealed a significant decrease in lung structural damage and collagen deposition in the radiation therapy plus AEOL 10150 (5 mg/kg BID) group, in comparison to radiation therapy alone.

Immunohistochemistry studies revealed a significant reduction in tissue hypoxia (HIF-1a, CAIX), angiogenic response (VEGF, CD-31), inflammation (ED-1), oxidative stress (8-OHdG, 3-nitrotyrosine) and fibrosis pathway (TGFb1, Smad3, p-Smad2/3), in animals receiving radiation therapy plus AEOL 10150 (5 mg/kg BID). Administration of AEOL 10150 at 5 mg/kg BID during and after RT results in a significant protective effect from long-term radiation therapy-induced lung injury.

“In addition to its support for the potential use of AEOL 10150 in cancer radiation therapy, this data supports the possible use of AEOL 10150 against radiation-induced tissue damage from radiological or nuclear terrorism and nicely complements ongoing studies showing AEOL 10150 as a potentially protective agent against chemical terrorist agents such as mustard gas,” stated John L. McManus, President and Chief Executive Officer of Aeolus Pharmaceuticals, Inc. “These studies collectively suggest that AEOL 10150 may be a potent counteract agent against multiple terrorist threats.”

Radiation therapy is used alone or in combination with surgery and chemotherapy in the care and management of nearly all adult and most pediatric patients with lung malignancies. Success in controlling lung cancer by radiation therapy hinges on being able to inactivate the cancer cells while preserving normal tissue function. The National Cancer Institute (“NCI”) estimates that there will be approximately 215,000 new cases of lung cancer in the United States and approximately 162,000 deaths. According to the NCI, “results of standard treatment are poor except for the most localized cancers.” The American Society for Therapeutic Radiology and Oncology reports that in 2004, nearly one million Americans made 23.4 million visits for radiotherapy treatments for cancer. The total market potential for an effective enhancement to current radiation therapy is estimated to be in excess of $1 billion.

The Potential for Metalloporphyrin Antioxidants in Radiotherapy for Cancer

Radiotherapy treatment in cancer has the positive effect of tumor destruction, but also has the negative effect of normal tissue damage. Optimal dosing in radiotherapy balances maximum tumor destruction with minimal toxicity and damage to normal tissue. The “ionizing radiation” used in cancer radiotherapy generates reactive oxygen species (“ROS”) and other free radicals. These free radicals cause DNA damage and cell death. Catalytic antioxidants, such as Aeolus’ AEOL 10150 and AEOL 10113 have been shown to neutralize free radicals and can reduce radiation-induced normal tissue damage. It is equally important that they also not protect the cancer from radiotherapy, which has been demonstrated in animal studies of both AEOL 10150 and AEOL 10113. A compound that protects healthy normal cells while not interfering with tumor destruction could provide patients and physicians the ability to either reduce side effects from cancer radiotherapy or to increase the radiotherapy dose, thus enhancing the potential for tumor destruction.

About Aeolus Pharmaceuticals

Aeolus is developing a variety of therapeutic agents based on its proprietary small molecule catalytic antioxidants, with AEOL 10150 being the first to enter human clinical evaluation. AEOL 10150 is a patented, small molecule catalytic antioxidant that mimics and thereby amplifies the body’s natural enzymatic systems for eliminating reactive oxygen species, or free radicals. Studies funded by the National Institutes for Health are currently underway evaluating AEOL 10150 as a treatment for exposure to mustard gas. Additionally, the Company has plans to initiate animal studies necessary to seek approval of the compound as a treatment to protect the lungs from exposure to radiation.

The statements in this press release that are not purely statements of historical fact are forward-looking statements. Such statements include, but are not limited to, those relating to Aeolus’ product candidates, as well as its proprietary technologies and research programs. Such forward-looking statements involve known and unknown risks, uncertainties and other factors that may cause Aeolus’ actual results to be materially different from historical results or from any results expressed or implied by such forward-looking statements. Important factors that could cause results to differ include risks associated with uncertainties of progress and timing of clinical trials, scientific research and product development activities, difficulties or delays in development, testing, obtaining regulatory approval, the need to obtain funding for pre-clinical and clinical trials and operations, the scope and validity of intellectual property protection for Aeolus’ product candidates, proprietary technologies and their uses, and competition from other biopharmaceutical companies. Certain of these factors and others are more fully described in Aeolus’ filings with the Securities and Exchange Commission, including, but not limited to, Aeolus’ Annual Report on Form 10-K for the year ended September 30, 2007. Readers are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof.

Aeolus Pharmaceuticals

Brain Development Steered By Newly Discovered RNA

How does the brain work? This question is one of the greatest scientific mysteries, and neurobiologists have only recently begun to piece together the molecular building blocks that enable human beings to be “thinking” animals.

One fundamental property of the mammalian brain is that it continues to develop after birth, and one of the biggest drivers of the formation of new links between neurons is experience. Every time a baby sticks her finger on a pin or laughs in response to an adult’s embellished gestures, a cascade of genetic activity is triggered in her brain that results in new, and perhaps even lifelong, synaptic connections.

New research from the lab of Michael Greenberg, Nathan Marsh Pusey professor and chair of neurobiology at HMS, in collaboration with bioinformatics specialist and neuroscientist Gabriel Kreiman, assistant professor of ophthalmology at Children’s Hospital, Boston, has found that a particular set of RNA molecules widely considered to be no more than a genomic oddity are actually major players in brain development – and are essential for regulating the process by which neurons absorb the outside world into their genetic machinery.

“This discovery may inform disorders of cognition such as autism spectrum disorders,” says Greenberg. “It’s incredibly important to know all about the brain’s genetic regulatory mechanisms in order to think more deeply about how to develop therapies for treating these sorts of conditions.”

This research will be published online April 15 in the journal Nature.

For over 25 years, Greenberg and his lab have been unraveling the mechanisms that enable the outside world to have a profound and lasting effect on neuronal genes. Broadly speaking, when a neuron is stimulated by an external excitation (the pin, the gesture), it releases chemicals called neurotransmitters (the most common one is glutamate). This neurotransmitter binds to a receptor on the neuron surface and then sets in motion a chain of events that affects the genetic activity of the cell. This in turn helps to modify the synaptic connections between neurons, which are the basis of learning and memory.

But what exactly happens inside of a cell after it is activated by neurotransmitter release?

To get closer to the cellular action, Tae-Kyung Kim and Jesse Gray of the Greenberg lab, in collaboration with Martin Hemberg from the Kreiman lab at Children’s, used two kinds of high-throughput, next-generation sequencing technologies, RNA-Seq and CHIP-Seq.

Working with mouse brain cells in culture, the researchers used RNA-Seq to identify, with great sensitivity, the RNA sequences that are newly synthesized when a neuron is stimulated in a manner that mimics the effect of a neurotransmitter, and which in turn touches off a domino-like cascade of intracellular signals. The researchers were then able to identify, sequence and – using CHIP-Seq – establish the genomic “address” and the regulatory factors that control the expression of all the genes switched on in these brain cells by the stimulus.

They discovered that there were individual and disparate stretches of DNA that appeared to be amplifying the genes’ activity, escalating the process of messenger RNA and protein production. These bits of DNA, called “enhancer regions,” were more often than not targeting their genes over vast genomic distances, like a computer dictating orders to a global digital network via satellite.

Most important, however, was the discovery that these enhancer regions accomplished this phenomenon by producing their own RNA molecules, and that these enhancer RNAs, or eRNAs, were intensifying the enzymatic processes that are essential for a gene’s ability to create protein.

“Biologists have known about enhancers since 1980, and there has even been a paper or two describing RNA produced at enhancer regions, but it was largely considered an isolated curiosity,” says Greenberg. “What we’ve discovered here is how widespread this phenomenon is. We’ve found that there are thousands of these enhancers, that they’re spread throughout the genome, and that they are essential to the process in which experience results in new synaptic connections. What’s more, we suspect that they’re active in many other mammalian cell types, not just neurons.”

It isn’t clear yet precisely how these eRNAs accomplish their synaptic-building tasks, or even where they travel to within the neuron once they are produced. These are questions for further study. Still, the researchers believe there is a likelihood that these finding may eventually prove relevant to, and cast light on, our understanding of certain neurological and psychiatric disorders in which the regulation of gene activity plays a critical role.

This research was funded by the National Institutes of Health.

David Cameron

Full Citation:
Nature, April 14, 2010, early online publication

Widespread transcription at neuronal activity-regulated enhancers

Tae-Kyung Kim1*{, Martin Hemberg2*, Jesse M. Gray1*, Allen M. Costa1, Daniel M. Bear1, Jing Wu3,
David A. Harmin1,4, Mike Laptewicz1, Kellie Barbara-Haley5, Scott Kuersten6, Eirene Markenscoff-Papadimitriou1{, Dietmar Kuhl7, Haruhiko Bito8, Paul F. Worley3, Gabriel Kreiman2 & Michael E. Greenberg1

1-Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, Massachusetts 02115, USA.
2-Department of Ophthalmology, Children’s Hospital Boston, Center for Brain Science and Swartz Center for Theoretical Neuroscience, Harvard University, 300 Longwood Avenue, Boston, Massachusetts 02115, USA.
3-The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, Maryland 21205, USA.
4-Children’s Hospital Informatics Program at the Harvard-MIT Division of Health Sciences and Technology, 300 Longwood Avenue, Boston, Massachusetts 02115, USA.
5-Molecular Genetics Core facility, Children’s Hospital Boston, 300 Longwood Avenue, Boston, Massachusetts 02115, USA.
6-Epicentre Biotechnologies, 726 Post Road, Madison, Wisconsin 53713, USA.
7-Institute for Molecular and Cellular Cognition (IMCC), Center for Molecular Neurobiology (ZMNH), University Medical Center Hamburg-Eppendorf (UKE), Falkenried 94, 20251 Hamburg, Germany.
8-Department of Neurochemistry, Graduate School of Medicine, University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan. {Present addresses: University of Texas Southwestern Medical Center, Department of Neuroscience, 5323 Harry Hines Blvd, Dallas, Texas 75390-9111, USA (T.-K.K.); Graduate Program in Neuroscience, University of California San Francisco, 513 Parnassus Avenue, San Francisco, California 94123, USA (E.M.-P.).

David Cameron
Harvard Medical School