SensiGen LLC, a privately held biotechnology company focused on developing proprietary gene-based molecular diagnostic tests announced today a new program to make the Company’s AttoSense™ HPV assay available to head and neck cancer researchers worldwide after recent studies showed that the success or failure of various treatment options (chemotherapy, radiation, extensive surgery) are largely determined by the viral load of Human Papillomavirus (HPV) in tissue samples from patients.

These studies, carried out by the Head and Neck Oncology Team at the University of Michigan and published in the Journal of Clinical Oncology, demonstrate that head and neck cancer patients with higher concentrations of HPV, a virus long known to be associated with head and neck cancer, cervical cancer, and others, are much more likely to respond to organ-sparing chemotherapy than patients without high concentrations of the virus. This finding could offer significant hope for thousands of head and neck cancer patients facing uncertain and unpleasant treatments.

“The data clearly show the importance of quantitative HPV testing in patients diagnosed with head and neck cancer,” said Dr. Thomas Carey, leader of the University of Michigan based team that reported the breakthrough results this summer. “With the AttoSense™ HPV test and other biomarkers, we may soon be able to pinpoint the right therapy for each patient and maximize the chance of success on the first try, thus reducing the number of people who must endure multiple costly and uncomfortable treatments.”

SensiGen’s AttoSense™ diagnostic assays are capable of accurately identifying minute quantities – in some cases as little as a single copy – of the biomarkers that signal the onset of major diseases or the pathogens that cause them. AttoSense™ HPV is the only assay in the world that can quantify and determine the presence or absence of each of the 15 known cancer causing forms of HPV, as well as calculate the relative “load” of the virus, all in a single, automated step.

“The AttoSense™ HPV test is the only assay that can reliably determine viral load for each HPV type at the 65 copies per cell threshold established by Carey et al.,” said Dr. Jay Stoerker, Vice President of Research and Development at SensiGen. “We currently support many such research studies worldwide in the area of cervical cancer, where HPV DNA testing is well established, but after the Michigan team’s breakthrough findings, we decided to launch a new program specifically for head and neck cancer research to bring the promise of the AttoSense™ technology to benefit the thousands of patients suffering from this disease.”

SensiGen’s new program will support head and neck cancer studies worldwide by providing education and training on the AttoSense™ technology and its application in HPV to research professionals and clinical investigators worldwide SensiGen is also discussing partnerships with independent reference laboratories to offer the AttoSense™ HPV test more broadly around the world.

“Since the results of Dr. Carey’s studies were published, interest in the AttoSense™ HPV test has been running high,” explained Shawn M. Marcell, President and CEO of SensiGen. “This is another example of an advanced molecular diagnostic test linking directly to targeted therapy, with enormous benefits not only in terms of better health care and reduced patient suffering, but reduced costs as well. We decided it was important to set up a formal program to meet the demands of the market and demonstrate this value.”

AttoSense™ HPV test kits are available for research use only (RUO). Parties interested in supporting or participating in the SensiGen head and neck cancer research program should contact the Company at 734-213-7600 or infosensigen.

About Head and Neck Cancer

Head and Neck cancers, which include oral cancer, cancers of the larynx and pharynx and others, account for about 3 to 5 percent of all cancers. In the US, about 40,000 new cases of head and neck cancer are diagnosed each year. The use of tobacco products, particularly “chew” or “snuff” products are highly associated with increased risk of head and neck cancer, along with other factors including alcohol use and HPV infection. Treatment options include chemotherapy, radiation therapy, and radical surgery. Many of the organs and tissues in the head and neck, such as the larynx and the pharynx, are in locations that are difficult to access for targeting radiation, applying chemotherapy, or conducting surgery, and hence, treatments for these conditions tend to damage adjacent tissues and cause increased patient suffering. Many patients are given a series of treatments before achieving desired results.

The AttoSense™ HPV test is a highly sensitive (98%+) and specific (99%+) multiplex assay that identifies the presence and quantity of all known oncogenic types of HPV in one step. The extreme accuracy versus conventional methods, attractive customer economics, and seamless fit with current laboratory practice offered by the AttoSense™ HPV Test are unmatched by any current or known methods. This assay is currently available for research use, and clinical trials are expected to begin in late 2008.

About SensiGen LLC

SensiGen is a biotechnology company focused on gene-based molecular diagnostics. The Company develops advanced high value diagnostic tests to enable early detection of diseases, aimed at improving standards of care and reducing overall health care costs. Current products in development include tests for early detection of human papillomavirus (HPV), the primary cause of cervical cancer, chronic kidney disease (CKD), Crohn’s disease, Lupus, and others. SensiGen’s proprietary molecular diagnostic assays offer dramatic improvements over current methods. sensigen

SensiGen™, AttoSense™ and EpiSense™ are trademarks of SensiGen LLC.

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Several newspapers recently published editorials and an opinion piece related to the Medicare prescription drug benefit. Summaries appear below.Arizona Daily Star: The “gist” of a report recently released by Government Accountability Office “is that it is very difficult for senior citizens to get accurate information about the various drug plans available because … many of the insurance company employees charged with explaining it don’t understand it themselves,” a Daily Star editorial states. Medicare prescription drug plans must improve the performance of call centers, but “Congress … should regard that as a mere stopgap measure until the prescription drug benefit can be molded into something that is more user friendly to a larger segment of the population,” the editorial concludes (Arizona Daily Star, 7/12).

Atlanta Journal-Constitution: Supporters of the Medicare prescription drug benefit said that beneficiaries “would choose the private coverage that met their needs at the lowest price, thus driving down costs through competition,” but, in “real life, senior citizens were forced to pick from between 40 to 50 competing plans in a system so complex that market forces and price signals became beside the point,” a Journal-Constitution editorial states. In addition, supporters said that “individual consumers would do a better job than government in lowering drug prices” under the Medicare prescription drug benefit, but, “again, reality disagreed” (Atlanta Journal-Constitution, 7/13).

Des Moines Register: The GAO report indicates that Medicare prescription drug plan sponsors “are confused about the Medicare drug benefit,” and “lawmakers should demand that the tax dollars going to insurance companies buy accurate answers when a senior calls with questions,” a Register editorial states. In addition, lawmakers should “revisit its mess and institute a government-administered drug plan that pools seniors together and leverages down the costs of drugs” (Des Moines Register, 7/13).

Rep. Candice Miller (R-Mich.), Detroit News: Medicare beneficiaries enrolled in the prescription drug benefit “are getting help in obtaining the life-enhancing and prolonging drugs they need despite attempts by Democratic critics — for purely partisan political reasons — to confuse and scare seniors away from signing up,” Miller writes in a News opinion piece. “In addition, the entire Medicare program may save money due to its efficiency in keeping seniors healthy, which means more savings for taxpayers as well,” Miller writes (Miller, Detroit News, 7/12).

Miami Herald: “The premise of Part D was that competition among private drug plans would drive down the cost of prescriptions,” but Medicare beneficiaries “must be able to accurately compare plan costs” for competition to work, the Herald editorial states. “If drug plans are so complex that they defy accurate description, how can seniors choose the best plan for their needs and, thus, drive down costs?” the editorial asks, adding, “They can’t” (Miami Herald, 7/13).

Raleigh News & Observer: The GAO report indicates that the performance of Medicare prescription drug plan call centers is “just not good enough,” and President Bush “ought to bring the hammer down on the insurers and drug companies he has treated so kindly,” a News & Observer editorial states. Bush “needs to disregard the defensive reaction to this investigation from the agency that supervises the program and demand action from agencies with organizational expertise to strengthen out the problems,” the editorial states (Raleigh News & Observer, 7/12).

“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. Continue reading →

Gov. Jim Doyle will be the first recipient of a prestigious award given by the nation’s largest group of ecologists at the 93rd Annual Meeting of the Ecological Society of America on August 3. The award recognizes a regional or local policymaker who has an outstanding record of informing their political decision-making with ecological science.

“We are pleased to honor a public figure that has a sharp appreciation for local and global ecological issues and works to use sound ecological science to inform decisions at the state level and beyond,” said ESA President Norm Christensen.

In his five years as governor, Doyle has demonstrated his commitment to ecological and environmental policy issues through his initiatives within Wisconsin and in collaboration with other states. As part of a task force centered on invasive species, he has more than tripled funding for local grants to fight aquatic invasive species within the state. In January, Doyle dedicated $6 million to purchase ballast water filtration systems to strengthen the harbors in Milwaukee, Green Bay and Lake Superior. Doyle serves as chairman of the Council of Great Lakes Governors, which works to update and improve the region’s water management regime.

Doyle has also created task forces on energy efficiency and renewable energy, including the Clean Energy Wisconsin Initiative, launched in March 2008. This comprehensive plan secured Wisconsin as national leader in environmental policy by promoting investments in renewable energy, creating “green” jobs and improving energy efficiency.

###

For more information about the award and the 2008 ESA Annual Meeting, visit esa/.

Source: Christine Buckley

Ecological Society of America Continue reading →

The U.S. Food and Drug Administration is warning consumers not to use 3.5 oz. packages of Swad brand sindoor, an orange or red powder used in some traditional South Asian Pacific ceremonies that is applied to the face or scalp, imported by Raja Foods LLC of Skokie, Illinois because the product contains high levels of lead. Although the product was not intended to be sold for food use, its labeling is confusing and implies that it may be used as food. The Illinois Department of Public Health has confirmed two cases of lead poisoning in consumers who used the product as an ingredient in home cooked meals. Other uses of the product, including as a cosmetic, can also be dangerous due to the high lead levels.

Lead can be toxic to all humans but due to the risks it poses to a developing nervous system, women of childbearing age, pregnant women and their unborn children, and young children should be especially cautious and limit their exposure to lead. Symptoms of lead toxicity include: stomach aches, colic, nausea, vomiting, abnormal irritability, and insomnia. However, people with lead in their blood often do not exhibit symptoms. Permanent damage to the central nervous system from lead exposure can result in learning difficulties in school children as well as cause other long-term health problems such as kidney disease. Anyone who has consumed this product should consult his or her health care provider immediately.

At least 280 packages of Sindoor were distributed to grocery stores that specialize in foods from India in Colorado, Georgia, Illinois, Indiana, Iowa, Kansas, Michigan, Minnesota, Missouri, Nebraska, New York, Ohio, Oregon, Tennessee, Texas, Washington, and Wisconsin.

The front label of the bag states “Swad Best Taste In Town Sindoor”, “For Recipe Ideas Visit Our Website: Www.Rajafoods”, and “Product Of India.” The back label states “Imported and Distributed by: Raja Foods, 8110, N. St. Louis Avenue, Skokie, ILL 60076″, with a UPC of 0 51179 42236 0 and may have a sticker stating “NONEDIBLE”.

Packages of Sindoor can be returned to the place of purchase for a full refund. Consumers with questions may contact the company at 1-800-800-7923 x 2860.

Consumers should report adverse events related to this product to MedWatch, the FDA’s voluntary reporting program: fda/medwatch/report.htm, 800-332-1088, fax: 800-332-0178, mail: MedWatch, Food and Drug Administration, 5600 Fishers Lane, Rockville, MD 20852-9787.

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A study carried out in a province of northern Iran where people drink lots of hot tea every day found there was a strong link between drinking very
hot tea and a higher risk of cancer of the oesophagus, the tube of muscle that carries food from the throat to the stomach.

The study was the work of Dr Reza Malekzadeh, professor and director of the Digestive Disease Research Center of Shariati Hospital at the Tehran
University of Medical Sciences, and colleagues, and was published online on 26 March in the British Medical Journal, BMJ.

The researchers suggest people wait a few minutes before drinking tea made with boiling water, since they concluded that drinking very hot tea (that is
at or above 70 degrees C or 158 degrees Fahrenheit) can raise a person’s risk of developing cancer of the oesophagus.

However, in an accompanying editorial, David Whiteman of the Queensland Institute of Medical Research in Australia said there was no cause for
alarm and advised people always to let hot food and drinks cool a little before swallowing them.

Oesophagal cancers, of which OSCC (oesophageal squamous cell carcinoma) is the most common, kill half a million people worldwide every year.
Tobacco and alcohol use is the most common cause in Europe and America and is more likely to affect men than women, however, a tendency to
consume hot drinks is also thought to play a role.

For the study, researchers went to Golestan Province in northern Iran because it has one of the highest rates of OSCC in the world, but women are just
as likely to get it as men, and the numbers of people who smoke and drink alcohol are quite low. On the other hand, lots of people drink hot
tea.

Malekzadeh and colleagues recruited 300 patients diagnosed with OSCC and matched them with 571 healthy people from the same area (the controls).
Nearly all the participants in both groups were regular tea drinkers, consuming on average over a litre a day.

They asked them questions about how hot they drank their tea and how long they waited after pouring it before starting to drink it.

The researchers then measured the actual temperature that nearly 50,000 people from the same area drank their tea at and compared it to the
participants’ description. The temperature ranged from under 60 to over 70 degrees C, and the researchers found that what the participants described
as the temperature agreed moderately with actual measurements.

The results showed that:

Compared with drinking warm or lukewarm tea (65 deg C or less), drinking hot tea (65 to 69 deg C) was linked to a doubling of the risk of
OSCC.
Drinking very hot tea (70 deg C or more) however, was linked to an eight-fold increased risk of OSCC.
Drinking tea within two minutes of pouring it was linked with a five-fold higher risk of OSCC compared to drinking it after four
minutes.
There was no link between how much tea people drank and risk of OSCC.

The authors concluded that:

“Drinking hot tea, a habit common in Golestan province, was strongly associated with a higher risk of oesophageal cancer.”

UK studies show that healthy people tend to report drinking tea at around 56 to 60 deg C.

The researchers said it was probably worth telling the people of Golestan and other high risk populations with similar drinking habits about the health
risk of having very hot drinks.

These findings are consistent with the idea that thermal injury may cause epithelial cancers, said Whiteman, though he pointed out that the underlying
mechanism is not clear and should be studied further.

However, Whiteman said people should not alarm themselves about these findings and hopes public enthusiasm for drinking tea is not diminished: just
let food and drinks cool from “scalding” to “tolerable” before swallowing them, he said.

“Tea drinking habits and oesophageal cancer in a high risk area in northern Iran: population based case-control study.”
Farhad Islami, Akram Pourshams, Dariush Nasrollahzadeh, Farin Kamangar, Saman Fahimi, Ramin Shakeri, Behnoush Abedi-Ardekani, Shahin Merat,
Homayoon Vahedi, Shahryar Semnani, Christian C Abnet, Paul Brennan, Henrik M??ller, Farrokh Saidi, Sanford M Dawsey, Reza Malekzadeh, Paolo
Boffetta.
BMJ 2009, 338:b929
Published online 26 March 2009
doi: 10.1136/bmj.b929

Sources: BMJ.

: Catharine Paddock, PhD

Continue reading →

Researchers may have uncovered why lung cancer afflicts some smokers and not others, according to data presented at the American Association for Cancer Research 100th Annual Meeting 2009.

“A history of smoking has always been thought of as a predictor of lung cancer, but it is actually not very accurate,” said Jian-Min Yuan, Ph.D., M.D., associate professor of public health at the University of Minnesota. “Smoking absolutely increases your risk, but why it does so in some people but not others is a big question.”

Yuan and colleagues hypothesized that the presence of the metabolite NNAL in a patient’s urine might predict risk of lung cancer. This metabolite has been shown to induce lung cancer in laboratory animals, but the effect in humans had not yet been studied.

Researchers collected data from 18,244 men enrolled in the Shanghai Cohort Study and 63,257 men and women from the Singapore Chinese Health Study. In addition to in-person interviews to assess levels of cigarette smoking, dietary and other lifestyle factors, researchers collected blood and urine samples from more than 50,000 patients.

To evaluate the impact of NNAL, researchers identified 246 current smokers who later developed lung cancer and 245 smokers who did not develop lung cancer during the 10-year period following initial interview and collection of urine samples.

Levels of NNAL in the urine were divided into three groups. Compared to those with the lowest levels, patients with a mid-range level of NNAL had a 43 percent increased risk of lung cancer, while those at the highest level had a more than two-fold increased risk of lung cancer after taking into account the effect of number of cigarettes per day, number of years of smoking, and urinary levels of cotinine on lung cancer risk.

Levels of nicotine in the urine were also calculated. Those with the highest levels of nicotine and NNAL had an 8.5-fold increase in the risk of lung cancer compared with smokers who had the lowest levels after accounting for smoking history.

“Smoking leads to lung cancer, but there are about 60 possible carcinogens in tobacco smoke, and the more accurately we can identify the culprit, the better we will become at predicting risk,” said Yuan.

Source:
Jeremy Moore

American Association for Cancer Research Continue reading →

Senate Finance Committee Chair Chuck Grassley (R-Iowa) and ranking member Max Baucus (D-Mont.) have introduced a bill (S 3987) that would provide federal and academic researchers with more access to data on hospital, physician and prescription drug services used by Medicare beneficiaries, CQ HealthBeat reports. The legislation would allow researchers to study the data to determine the safety and effectiveness of various services, Grassley in a statement said. Under the bill, FDA, CDC, NIH, the Agency for Healthcare Research and Quality and academic researchers would receive access to the data, provided that they publish the results and methodologies of their studies. The Congressional Budget Office, Congressional Research Service, Government Accountability Office and the Medicare Payment Advisory Commission also would receive access to the data to help them meet their responsibilities to Congress. Grassley and Baucus said that the bill would ban the release of data on specific health care providers, the sale of the data and the use of the data for commercial purposes. In addition, they said that the legislation would require researchers to meet standards to receive access to the data (Carey, CQ HealthBeat, 9/18). Researchers also would have to submit plans on their use and protection of the data and would have to receive approval from a review board on the protection of human study participants (CongressDaily, 9/19). Grassley said, “Researchers could help us better understand why services that we know can help people maintain good health are not being used and to develop policies to promote their use.” Baucus said that the bill would allow federal agencies to partner to study services provided to a large segment of the population, which could help improve the U.S. health care system (CQ HealthBeat, 9/18).

“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. Continue reading →

A shorter more intensive course of radiation therapy that lasts three weeks as opposed to the standard five appears to be just as effective for treating
early stage breast cancer said researchers at a conference in Boston on Monday.

The results of a randomized long term study comparing the two therapies were presented by lead author Dr Timothy Whelan who is a radiation oncologist at the
Juravinski Cancer Centre at McMaster University in Hamilton, Ontario, Canada. Whelan presented the findings at the plenary session of the 50th Annual
Meeting of the American Society for Therapeutic Radiology and Oncology.

Many women with early stage breast cancer have breast conservation treatment comprising surgery to remove the cancerous growth (a “lumpectomy”) followed by 5
weeks of standard radiation therapy on the whole breast to kill off any remaining cancer cells. The treatment typically consists of 15 minutes of daily
therapy from Monday to Friday for five weeks.

Whelan and colleagues tested a shorter treatment comprising a more intensive course that also irradiates the whole breast but it only lasts three weeks.

They found the shorter course was just as effective and they also suggested it offered patients more convenience at lower cost, which meant a better quality
of life.

The new shorter treatment is called “accelerated hypofractionated whole breast irradiation” and is one third cheaper than the standard five week course, and
is also less costly than other new methods such as those that only irradiate part of the breast.

Whelan said while the new method had attracted a lot of interest, mainly because it was cheaper and more convenient, there was insufficient evidence of its
long term effectiveness which is why they carried out the study.

“We were surprised that the risk of local recurrence and side effects for women treated with accelerated whole breast irradiation was so low even at 12
years,” said Whelan.

“Our study shows that this treatment should be offered to select women treated with early-stage breast cancer,” he added.

For the study, Whelan and colleagues recruited 1,234 women seeking treatment for early stage breast cancer from April 1993 to September 1996. Each woman was
randomly assigned to either receive accelerated whole breast irradiation or the standard whole breast irradiation treatment.

The women were then followed for 12 years after treatment. The results showed that at 10 years after treatment, the cancer had returned locally in 6.2 per
cent of the accelerated treatment group compared to 6.7 per cent of the the standard therapy group. Cosmetic outcomes were excellent in both groups, said
the researchers.

Whelan concluded that:

“This shorter treatment may not be for everyone, however, I would encourage women whose breast cancer is caught early to talk to their oncologist to see if
they are a good candidate for this shorter therapy.”

The press report did not mention where they were intending to publish the study.

After skin cancer, breast cancer is the most common cancer among women in the United States, and it is the second leading cause of death in women after lung
cancer, according to the American Cancer Society (ACS). The chance of a woman developing invasive breast cancer sometime during her life is about 1 in 8 and
the chance of dying from it is about 1 in 35.

The ACS estimates that about 182,460 women in the US will be diagnosed with invasive breast cancer in 2008 and nearly 40,500 will die of the disease. There
are currently 2.5 million breast cancer survivors living in the US.

Rates of breast cancer deaths are going down, probably as a result of earlier detection and improved treatment, said the ACS.

Long-Term Results of a Randomized Trial of Accelerated Hypofractionated Whole
Breast Irradiation Following Breast Conserving Surgery in Women with Node-negative Breast Cancer.”
Whelan, T, et al.
Presented at the plenary session at 2:00 p.m. on Monday, September 22, 2008.
At the 50th Annual Meeting of the American Society for Therapeutic Radiology and Oncology in Boston, USA.

Source: American Society for Therapeutic Radiology and Oncology, American Cancer Society.

: Catharine Paddock, PhD

Continue reading →

Pharmacies can charge health insurers an 18% premium on the cost of medications and receive a dispensing fee of about $2.27 cents per prescription under the Medicare prescription drug benefit, according to a report released on Thursday by the HHS Office of Inspector General, the AP/Houston Chronicle reports. According to the report, pharmacists receive $2 less in dispensing fees for prescriptions filled under the Medicare prescription drug benefit than they receive for prescriptions filled under Medicaid.

The Association of Community Pharmacists said that the report confirms that reimbursements for prescriptions filled under the Medicare prescription drug benefit are inadequate and have forced many community pharmacies to close. The 18% premium that pharmacies can charge does not cover all of their costs, such as employee wages, taxes and utilities, ACP said.

ACP Government Affairs Director Mike James said that most community pharmacies would have to charge a 20% to 21% premium to remain in business. More than 1,100 community pharmacies closed last year, and many cited inadequate reimbursements for prescriptions filled under the Medicare prescription drug benefit, James said.

The report — requested by 33 senators after community pharmacies complained about reimbursements for prescriptions filled under the Medicare prescription drug benefit — did not include a recommendation on whether the payments are adequate. The senators who requested the report likely will seek additional information (AP/Houston Chronicle, 1/10).

The report is available online.

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© 2005 Advisory Board Company and Kaiser Family Foundation. All rights reserved. Continue reading →

The same protein that “translates” sound into nerve signals to the brain and enables individuals to hear is also required
for pain perception, researchers from Northwestern University Feinberg School of Medicine have found.

Because the protein, TRPA1, is found in the majority – about 75 percent — of the body’s pain-perceiving neurons, but not in
major organs, drugs that could block TRPA1 would be novel pain killers with few or no side effects, although targeting the
inner ear may have to be avoided, said Jaime Garcia-A?overos, who led the research.

Garcia-A?overos, assistant professor of anesthesiology, neurology and physiology at Feinberg and the Northwestern University
Institute for Neuroscience and a fellow of the Hugh Knowles Center for Hearing Research, described the dual role of the
protein, TRPA1, in the cover article of the April 20 issue of the Journal of Neuroscience. The other authors, all members of
his research group at Northwestern University, were Keiichi Nagata, Anne Duggan and Gagan Kumar.

Garcia-A?overos and his colleagues showed conclusive evidence that TRPA1, in addition to being expressed in nociceptors, or
pain neurons, is present in the stereocilia of hair cells, the sensory part of the cells of the inner ear used for hearing as
well as detecting gravity and maintaining balance.

Garcia-A?overos and Duggan, currently a research assistant professor in anesthesiology at Feinberg and a researcher at the
Northwestern University Institute for Neuroscience, initiated the study of TRPA1 in the late 90s, while searching for the
channel that mediates hearing.

After they discovered that TRPA1 is expressed in the organ of Corti, the hearing organ of the inner ear, they were joined by
colleagues at Harvard Medical School and Northwestern, and thus founded the groundbreaking group of scientists who in 2004
proposed that TRPA1 was a candidate for mechanosensory channel of hair cells.

In the current study, the Northwestern researchers also demonstrated that TRPA1 channels display a unique combination of
properties displayed by the hair cell transducer and by no other known channel. These similarities strongly suggest that
TRPA1 is the pore that opens in response to sound, initiating the electrical signal cascade that ultimately reaches the brain
as we perceive sounds.

But the researchers have also found properties of the TRPA1 channel that account for its suspected parallel role in pain
sensation, such as why in some cases pain from an injury will not go away as long as the injury remains.

Essentially, TRPA1 opens in response to painful stimulation, and ions enter the cell, making it less negatively charged, or
depolarized. At this point most ion channels close, a phenomenon known as inactivation, because their signaling task has been
achieved.

But TRPA1 senses the depolarization and responds to it by staying open; it will close only when the harmful stimulus goes
away. However, if the depolarization is small, the TRPA1 channels close.

This means that TRPA1 could allow sensory neurons to ignore sustained innocuous stimuli (such as gentle pressure) but to
respond to noxious stimuli (such as a pinch that causes tissue damage) and remain active as long as the noxious stimuli
persist.

It also means that TRPA1 is sensitized by the opening of other nociceptor channels in the same sensory nerves; for example,
those that respond to painful heat. This property of TRPA1 may thus account for painful phenomena in damaged tissues such as
lack of desensitization or even some forms of enhanced sensitization, such as hyperalgesia (extreme sensitivity to pain) or
allodynia (pain resulting from non-noxious stimuli to normal skin).

“Now we can look for TRPA1 channel blockers, which potentially will constitute novel analgesics that block pain at its
initiation,” Garcia-A?overos said.

“Such TRPA1 channel blockers should probably be used topically – preferably avoiding contact with the inner ear – but could
also be applied systemically. In that case the patient might have to put up with temporary deafness, a side effect that is
probably better than extreme pain. What is critical at this point is to identify drugs or treatments that very specifically
inhibit TRPA1,” he said.

TRPA1 is known to be activated by pain-producing chemicals such as the pungent components of edibles such as wasabi,
horseradish, mustard, cinnamon and Listerine®, which explains why they sting the mouth.

The full article is available online at: jneurosci
[25(16):4052-4061].

Contact: Elizabeth Crown
e-crownnorthwestern.edu
312-503-8928
Northwestern University
northwestern.edu Continue reading →