We were at Handyman Robinsons Place Manila last Friday for Handyman?s Family Day 2012.
Handyman prepared activities for the kids and the whole family including art class for kids, home improvement demos, raffles, etc.
The main activity for the families was the Booth Challenge. Handyman setup 9 demo booth stations for this challenge.
Upon registration, each family was given a Family Day Passport with a map of the booths. Our goal was to visit all booths and earn a stamp from each booth by completing the task/challenge prepared by the individual booths. A clue is given after completion of each of the booths? challenges. The clues were then used to guess the mystery item. The final challenge was to retrieve a sticker from the mystery item.
Here are some photos we took as we went around the booths.
First booth, Pr1mero. Pr1mero is a sealant company. The ?photo below shows a newspaper applied with their water-based transparent sealant product. See how it holds the water.
Command Brand, provides hanging solutions ? hooks, strips, etc. for office and home use
?Eco Sense products helps reduce water consumption
The Skil Power Tools. We had our hands on the Cordless Drill/Driver. The Skil power tools are really cheap, the photo below (on the left) shows a 4-pc combo pack which includes a cordless drill, saw, flashlight for just Php 7,000 .
Baygon booth
Black and Decker. The Black and Decker?s cordless drill/driver is priced at Php 5,000, a bit pricey but it?s Black and Decker. ?
Firefly Lighting booth.?
Do It Best booth.
Last booth is from Breville Philippines. Breville provides Kitchen, Food, Beverage and Cooking products. This may be the best challenge. We were served a dice of pizza and was asked to name at least 4 ingredients. ?
Mission Completion!
Art class for kids.
Happy Lemon. Some refreshments after the challenge
The beautiful people of Handyman Robinsons Manila.
Families who completed the challenge all came home with a loot bag. The first five families who completed the challenge won special prizes. Handyman also selected 5 raffle winners which received Php 20,000 worth of Cebu Pacific Gift Certificates.
We had an amazing day at the Handyman?s Family Day. The activity did not only provide entertainment for the families but also allowed the families to learn about the various Handyman home improvement products.
Our place is near the mall and I always go to Handyman whenever I need something for my home or even for my car.?Handyman is a big store and they have everything I need most of the time.?The staff are also accommodating and knowledgeable about their products. Again,?Congratulations to Handyman! Looking forward to visiting your store again. Cheers!
Check out Handyman Philippines? website, Facebook page?and Twitter?for more.
For Handyman Philippines? branches, click here.
About Handyman
Robinsons Handyman, Inc. was first established as a company in July 1994 and began operating with the opening of its first branch, Robinsons Handyman Home Improvement Center, in Robinsons Galleria. Handyman introduced to the public the convenience of hardware shopping in malls. Over the years, it has grown to be one of the most aggressive hardware and home improvement centers in the country. In 2002, Handyman became a member of the Do It Best Corporation, one of the biggest hardware cooperatives in the United States. With this, Handyman is able to bring to the Philippine market thousands of affordable, high quality imported products meant to provide the various needs of homeowners, project owners, builders and designers for repair, home improvement, renovation and construction. There are over thousands of items for gardening, pet care, automotive and motorcyle, home safety and security, electrical and wiring devices, building materials, lumber, flooring and tiles, paint and chemicals, hardware, houseware and home improvement merchandise that Handyman carries.
Today, Handyman has a wide network of stores located in all Robinsons malls, all WalterMart shopping centers, and other key commercial landmarks in all over the country. Handyman is part of Robinsons Retail Group.
An IT Developer, MP3 DJ, photo fanatic and a dad. My take on urban living, photography, tech, music, fatherhood and just about anything that holds fascination to me
http://daddyjoey.com/?
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Study product creation with the expert ; get Product eClass. This product is a popular training course brought to you by somebody who has attained one million dollars from his online ventures alone. Jason Fladlien has many hundreds of digital products on his list. He founded the Rapid Crush Software Club with his partner, the equally brilliant Wilson Mattos. Together they?ve already developed a reputation of being able to offer simple but groundbreaking digital product approaches.
Wanna learn how they?ve gained success? You are in luck! Jason has developed a training program that?s exactly about the process of creating his digital products? as well as how he profits from these products!
So, What Is This Thing Known As Product eClass 2.0?
Product eClass 2.0 is an updated version of this particular training package, which had its initial launching a couple of years back. As part of his recently updated product, we get many brand new concepts from Jason. These are the things he has learned directly from his activities as a successful entrepreneur throughout the years. To get data and resources for this article, please be sure you look at Product eclass.
More On Product eClass
Within the Product eClass 2.0 training program, we get to study the best way to develop digital products. We?re also taught how to do these quickly, in 2 hours. The six-week group training course will be coached by Jason himself. Thus, we can ask whatever we want and he will answer them! Furthermore, he can lead us over a product creation endeavor so that by the end of the program, we shall have created about three of our own products. When we register, we are then distributed transcripts and videos of the instructions. Yet, quite possibly the most vital component of Product eClass 2.0 are the live sessions along with Jason Fladlien .
Worthwhile stuff we learn through Product eClass are:
* Tips on how to price your product low yet obtain a substantial earning * The steps to making titles that sell to bring in the right niche market * Making info products in a step-by-step format * The best way for you to drive traffic towards your blog * The best way to boost revenue from just 6 to seven figures * Just what your digital product should be selling * Steps to being an affiliate marketer * How to stretch prices * Doing the 1-1-1 Product Creation Formula
Jason?s 1-1-1 Product Creation Formula As Mentioned in Product eClass
To illustrate a very basic but highly effective product creation rule coming from Jason Fladlien, we will examine the 1-1-1 Formula. As outlined by Jason himself, speed is all-important for the results of this kind of endeavor. Accordingly, anyone should be able to generate one product in a single sitting, and it ought to contain a single challenge and produce one answer to the problem: 1 sitting, 1 issue, 1 answer. As simple as this.
How Much is Product eClass 2.0?
If you are thinking just how much you will need to spend to own this best selling product that could make you earn long lasting income from your internet pursuits, four hundred ninety-five dollars is the fee. With just this fee, Jason gives you six limited-supply bonuses besides Product eClass . These bonuses come from a selection of Jason Fladlien?s own products:
* The Master List * Traffic eClass * Two-Day Amazon Book * Three Unique Products With Resell Rights * The Sales Conversion Templates * Master eBook Templates
Aside from that, Jason is offering thirty- and sixty-days cashback guarantees. The thirty-day full money back guarantee is a straightforward offer for unhappy customers, while the sixty-day offer is a double-moneyback guarantee for people who took the tutorials but didn?t receive the advertised earnings in two months. In case you want some more web facts on internet marketing in general, see this link.
I sat astride my banana seat bike in a parking lot and stared down a thirty foot strip of pavement. It was six inches wide and lined with rubber balls. I was nine years old and participating in a bicycle rodeo. The objective was to ride the entire length without hitting a single ball. The slightest bump would send them rolling.
Nearly a hundred kids had entered, and so far no one had done this event perfectly. Each contestant got three tries. The best hit only five balls, most hit dozens. I didn?t see the difficulty. It looked easy, and as it turned out, for me, it was. I did it on my first attempt. No one else was able to do it ? even with three tries. I was able to do it for the simple reason that I believed I could.
Decades later, riding my mountain bike, I attempted to ride a 20 foot length of six-inch board that was elevated 12 inches off the ground. I was lucky if I could complete the length one try in twenty. That measly 12 inches of doubt shattered my belief system. As Henry Ford said, ?If you think you can or you think you can?t, you?re right.?
We?ve seen sports stars whose belief system took them to the top of their game: Michael Jordan swooshing the net for a lifetime average of 30 points per game; Tiger Woods routinely sinking impossibly long putts of 50 feet or more; and Babe Ruth pointing to the outfield fence where he would hit a home run. What is their secret? Other than the thousands of hours of practice, which many lesser players also have, each of these men visualized what they wanted to achieve then allowed themselves to do it. Their belief put them ?in the zone.? When our belief is strong enough, we will succeed. Or as Buddha put it, ?We are what we think. All that we are arises with our thoughts. With our thoughts, we make the world.?
Is there something you believe you can do, but you?ve never tried? Many years ago I was president of my neighborhood association. Each month I had to give a brief speech that amounted to little more than giving announcements. Nevertheless, it made me extremely nervous and I clung to the lectern in a white-knuckle grip as I read my notes out loud.
During that time, I participated as a counselor to a group of teenagers attending a Hugh O?Brian Youth Foundation leadership seminar. The Saturday night dinner keynote speaker was entertaining and informative; she was also relaxed and clearly having fun. I remember thinking to myself, ?I can do that. I want to do that!? In those two succinct sentences I made a belief statement and a desire statement, both of which are necessary for success.
I genuinely believed that I could speak professionally because I had told many a good story across a dinner table, but at the same time I remembered how I felt speaking to the neighborhood association with a stomach full of butterflies. To combat those feelings I joined a Toastmasters club and learned what I didn?t know about public speaking.
It took me a year before I could break free of the lectern and my notes. Two years after that I started speaking professionally. I gave presentations on advertising which is the industry I?ve worked in most of my life, but more than anything I wanted to speak on innovation and creativity.
During my first year or two of speaking, I met a nationally known professional speaker. He asked me what topic I spoke on and I replied, ?Creativity.? He scoffed at that and said, ?There?s hundreds of guys speaking on that ? you need to find your own niche.? On that advice I developed some additional topics, but soon found that the presentation which led to the most recommendations was the one on creativity. What was the difference? It is a subject that I am passionate about. Creative thinking has improved my life time and time again, and it is my belief that it will help others. When I speak on it, I am in the zone.
Is there a business you believe you would be successful in? You would not be dreaming about it ? seeing yourself doing it ? if you didn?t believe you could! Michael Jordan didn?t become a basketball star without developing the skills he needed first. He took as many as 2000 practice shots a day to imprint those skills into his mental and physical circuitry. Perhaps all you need is practice.
If there is something you want to do, but haven?t tried, then break it down. What parts of the business do you believe you can do? What parts do you believe you can?t do? Do the parts you can do outweigh the ones you can?t? If yes, then you?re off to a good start, and the odds are in your favor. But if the opposite is true, don?t let that stop you. Belief must be supported by desire. If your desire is strong enough, you will gain the skills and subsequently the self-belief you need to succeed.
Once you?ve identified the parts you can?t do, ask yourself, ?Can I learn to do them?? If not, hire someone else who can. Perhaps you don?t even know which parts you don?t know. That?s OK; hire a consultant, or talk with someone who has already succeeded at this or a similar business. Delegating what you can?t do, frees up your belief system and enables you to focus on what you can.
When you believe you can do something ? you don?t really think about it ? you just do it. It?s the thinking about it that sometimes holds you back. According to David Eagleman, in his book Incognito: The Secret Lives of the Brain, if you?re getting trounced in tennis, ask your opponent how they are able to serve so well. He says that will cause them to start thinking about how it is done to the point that they won?t be able to do it anymore. Are you over-thinking your desire?
In my research of creative thinkers and innovators, the one trait I found that was nearly universal among them was the belief that they will succeed. They believe they will be able to create whatever it is they have set out to create. They believe they will be able to solve the problem they are facing. Thomas Edison may have expressed it best, ?I have not failed 700 times. I have not failed once. I have succeeded in proving that those 700 ways will not work. When I have eliminated the ways that will not work, I will find the way that will work.?
What are you waiting for ? if you believe you?ll succeed ? you will. Go for it!
Robert Evans Wilson, Jr. is an author, humorist and innovation consultant. He works with companies that want to be more competitive and with people who want to think like innovators. Robert is also the author of the humorous children?s book: The Annoying Ghost Kid. For more information on Robert, please visit http://www.jumpstartyourmeeting.com.
It?s time again for Non-Consumer Mish-Mash, where I write a little bit about this and a little bit about that.
Counter Culture
After 16 years in a fixer-upper home, my husband is sick and f*@&ing tired of working on household projects. The easy and cheap projects are behind us, and what?s left is dull, expensive and not even slightly fun. So imagine my surprise when my husband excitedly told me this morning about a countertop that he saw in a bar last night. (He plays on an adult soccer team, and they went out for beers after practice.) It was stained concrete, and somehow, it sparked his deeply buried motivation for home improvement projects.
Our current kitchen countertops are inoffensive Formica with an oak edging that I?ve hated since the day we installed it. But the nasty, nasty counters from the previous owners needed to go, so we slapped down the cheapest option Home Depot had to offer. (Our house was uninhabitable when we bought it in 1996, and I am not exaggerating. We had to work on it for a full year before we could even move in!)
So now my husband and I have a date planned to check out the bar and countertop. Color me excited.
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Is Your Right to Resell in Peril?
There is an upcoming Supreme Court case that?s catching the eye of many Non-Consumer Advocate readers. The newsworthy case involves a university student who discovered that English language textbooks sell for substantially less in his native Thailand than they do here in the U.S. So this entrepreneurial student set up his own eBay business.
Here are the details from the Wall Street Journal:
?The case stems from Supap Kirtsaeng?s college experience. A native of Thailand, Kirtsaeng came to America in 1997 to study at Cornell University. When he discovered that his textbooks, produced by Wiley, were substantially cheaper to buy in Thailand than they were in Ithaca, N.Y., he rallied his Thai relatives to buy the books and ship them to him in the United States.
He then sold them on eBay, making upward of $1.2 million, according to court documents.
Wiley, which admitted that it charged less for books sold abroad than it did in the United States, sued him for copyright infringement. Kirtsaeng countered with the first-sale doctrine.
In August 2011, the U.S. Court of Appeals for the Second Circuit upheld a lower court?s ruling that anything that was manufactured overseas is not subject to the first-sale principle. Only American-made products or ?copies manufactured domestically? were.
?That?s a non-free-market capitalistic idea for something that?s pretty fundamental to our modern economy,? Ammori commented.
The Supreme Court is scheduled to hear oral arguments on the case on Oct. 29.?
I?m not worried about how this will affect occasional resellers such as myself. There is no way that law enforcement would be able to track vintage resellers, let alone take an interest in little ol? us. However, I will pay attention to the Supreme Court verdict.
Super interesting.
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Flea Market Renoir Had Been Stolen
Do you dream of finding a priceless painting at a flea market, flea market or garage sale? Well, a recent flea market Renoir sale was halted recently, when it was discovered that the painting had been reported as stolen in 1951.
I feel bad for the seller, who must have already spent the expected $75,000 in her head. Not her fault she was holding onto stolen goods.
Such a bummer, but that?s not going to stop me from keeping an eye out for priceless paintings when I go thrifting. You never know . . . .
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Could You Live Without Money?
An article from Shareable.com titled A Life of Abundance Without Money?recently caught my eye. The article focused on Daniel Suelo, age 51 who has chosen a life dedicated to living without earning or spending any money. Eating perfectly good food from dumpsters, Suelo is bringing attention to the waste within our own society, blogging?from the library computers and giving interviews. (I took a quick look though his blog, and please know I am not endorsing his ideas!)
?I?m not even sure what poor really means, because I don?t feel like I?ve been lacking since I gave up money. I feel in a lot of ways more wealthy and not so limited.?
It?s an interesting article, and worthy of attention. Of course, it?s not a lifestyle that many of us would sign up for, but there?s still food for thought.
Katy Wolk-Stanley
?Use it up, wear it out, make it do or do without?
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BANGKOK (AP) ? Asian stock markets were mixed Friday after U.S. jobless claims plummeted unexpectedly, with analysts saying more data was needed to confirm an actual improvement in the world's No. 1 economy.
Weekly applications for unemployment aid fell to their lowest since February 2008, the U.S. government said Thursday. The positive figures follow a report last week that said the unemployment rate fell in September to 7.8 percent ? below 8 percent for the first time since January 2009.
Still, the job news isn't all that strong. Unemployment is much higher than before the financial crisis. In February 2008, the rate stood at 4.9 percent. Additionally, some unemployed workers have simply given up looking for work, which can make the jobless numbers seem better than they really are.
"I think you need to wait for a few months to see more figures to confirm the jobs recovery in the U.S.," said Francis Lun, managing director of Lyncean Holdings in Hong Kong.
Hong Kong's Hang Seng advanced 0.5 percent to 21,100.76 and Australia's S&P/ASX 200 added 0.1 percent to 4,487.20. South Korea's Kospi was flat at 1,932.18.
Japan's Nikkei 225 index was fractionally lower at 8,544.72. Telephone company Softbank plunged 15 percent in Tokyo on news that it is in talks to take a substantial stake in U.S. carrier Sprint Nextel Corp. Fast Retailing fell 9.9 percent after the Uniqlo casual clothing firm reported a first-half operating profit that missed market expectations, Kyodo News reported.
Other economic developments Thursday hurt investment sentiment.
The U.S. Commerce Department reported that foreign demand declined for American-made cars and farm goods. German economic researchers predicted the country's growth would slow, and unemployment in Greece, one of the countries surviving on bailouts, hit a record high of just more than 25 percent.
One big unknown is Spain and whether the government of the recession-mired country will ask for a financial bailout.
Last month, the European Central Bank agreed to buy unlimited amounts of debt by struggling European countries to help lower their borrowing costs. But the governments first need to apply for bailout.
Spain has not applied. Instead, the government has introduced a series of austerity measures in a bid to bring down its deficit and convince investors it can manage its finances without outside help.
"For the day ahead, attention will likely shift to the US earnings reports, with JP Morgan and Wells Fargo in focus while uncertainty about the Spanish bailout will remain as a significant downside risk in the eurozone, leaving sentiment cautious," analysts at Credit Agricole CIB in Hong Kong said in a market commentary.
Macau gambling shares did well following what analysts said was reportedly good revenues following the China's Golden Week holiday. Sands China Ltd. jumped 4.4 percent and Wynn Macau Ltd. rose 1.5 percent.
On Wall Street, the Dow Jones industrial average fell 0.1 percent to 13,326.39. The Standard & Poor's 500 rose marginally to 1,432.84. The Nasdaq composite index fell 0.1 percent to 3,049.41.
Benchmark oil for November delivery was up 8 cents to $92.15 per barrel in electronic trading on the New York Mercantile Exchange.
In currency trading, the euro dropped to $1.2929 from $1.2934 late Thursday in New York. The dollar was unchanged at 78.31 yen.
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Follow Pamela Sampson on Twitter at http://twitter.com/pamelasampson.
Many big banks still aren't being upfront about their checking account fees and are even charging more for some basic functions, a new study says.
?The study, by Pew Charitable Trusts, says that 12 major banks have shown little progress toward transparency in the past 18 months.
?Some fees were not listed at all on bank websites, while others were only available if customers used the websites' search box, says the study, a follow-up to an April 2011 report.
CNBC.com: Why home refinancing boom is different this time
?Even the most common fees, the report charges, are sometimes obscured in long disclosure statements.
??The median length of bank checking account disclosure statements has decreased,? the report says, ?but is still cumbersome at 69 pages.?
The battle over banking fees has been building since last fall, when federal regulators capped the amount banks may charge merchants for debit card transactions. In the first quarter of this year, Wells Fargo saw a 32 percent drop in revenue from debit card purchases from the same period in 2011. At the same time, the cost of keeping deposits has gone up, due chiefly to higher premiums paid to the FDIC for deposit insurance.
Banks have looked to checking fees, especially those for using other banks? ATMs, and for using overdraft protection to make up the loss, pointing out that customers have to pay for checking services somehow.
CNBC.com: Planning for retirement? Don?t forget health care costs
But watchdogs like Pew have voiced suspicions that the banks are overcompensating, looking to make profits by unfairly driving up penalties. The report stops short of calling the banks predatory, but it casts doubt on banks? protestations that the fees are only reasonable.
Wednesday's report notes, for instance, that some banks let larger overdrafts hit customers? accounts first, ensuring multiple overdrafts. Banks ?can maximize the number of overdrafts by reordering deposits and withdrawals in such a way as to reduce the account balance as quickly as possible,? the Pew researchers wrote.
While focusing on the most common charges, Pew also chides the banks for tagging customers for such exotica as, ?empty envelope,? ?bad address,? ?online images and photocopy requests? and "domestic wire transfer email notification.?
CNBC.com: Need a bigger home? Swap with Mom and Dad
The report cautioned that credit unions, traditionally a refuge from high bank fees, are not necessarily any better than the major banks. Seven of the 12 credit unions studied ?reserve the right to order a customer?s transactions from high to low,? the report says.?
The report also complains that information about some crucial fees didn?t appear on some credit unions? websites. The fact that the credit unions don?t charge such fees was no excuse: The lack of a charge should be clear, the report says, for the purposes of comparison shopping.
CNBC.com: Foreclosures plunge, but new states now suffer
Pew did find some meager reasons to cheer. The most common fees, penalties for overdrafts, are largely unchanged from 18 months ago. And some banks have shown more willingness to disclose information, albeit mostly when they had good news ? twice as many banks now advertise that they won?t overdraw your account for a minimum amount ? saving customers a $35 charge for that $5 cup of coffee, say.
Most overdrafts are closer to $36, however, an amount that immediately kicks in a median charge of $35 ? or 5,000 percent annual interest on what the bank fronts the customer. Calling that "excessive," Pew makes a recommendation that is remarkable mostly in that it needs to be stated at all: Fees, Pew says, should be "proportional to the financial institution?s costs in providing the overdraft loan or to the size of the overdraft itself.?
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TAIPEI, Taiwan (AP) ? Taiwan is asking Apple Inc. to blur a map image of its new $1.4 billion early warning radar station that can detect aircraft and missiles coming from as far as western China.
Defense Ministry spokesman David Lo said Tuesday that Apple should follow its rival Google in using only low-resolution satellite pictures to show sensitive facilities. He acknowledged the military should also try to camouflage them.
The 10-story high radar installation built with U.S. technology is expected to go online later this year. It's near the Hsinchu Air Base in northern Taiwan.
The satellite picture that can be viewed with iPhones is believed to have been taken a year ago.
Local media say the radar installation can monitor targets, determine their speeds and fire missiles to intercept them.
Digital media is premised on innovation. It is the lifeblood of agencies and can be a calling card for brands. But it is, also, often enough, an exercise in public relations. Many publications, Digiday included, are eager to be the ?first? to something or other. The result is many ?innovations? are really closer to PR stunts that are measured not on business results or even R&D but on ?earned media.? There are even times, shockingly, that these things are done by agencies in the hopes of winning awards.
The downside of that is what?s been termed ?bright, shiny object? syndrome, where an article on Mashable or Fast Company sends brand managers scrambling to ?get me one of those.? There?s a reason so many brands rushed into Second Life, after all. Aaron Shapiro, CEO of Huge, said during Advertising Week that many clients are so distracted by the New New Thing that they neglect the basics that can actually change their businesses.
With this in mind, Digiday is starting a series that will examine the relative merits of a new talked-about effort to determine which it is: genuine innovation or PR exercise. We?ll list the case for each and invite you to weigh in on the comments, on Twitter, on Facebook or through good old-fashioned email. Please also send along nominations for future installments of ?Innovation or PR??
This week we look at the Lexus print campaign with Sports Illustrated that lets users bring a print ad to life with their iPads.
Lexus and agency TeamOne have developed technology called CinePrint that has allowed what it bills a ?print-digital ad mash-up? in the new issue of Sports Illustrated. Here?s what happens: Readers of Sports Illustrated take the print ad and place it over their iPad screen when it?s showing the iPad edition of Sports Illustrated or a specific page of the Lexus website. The ad then ?comes to life? with sight, sound and motion by playing images that shine through the page. It makes it appear as though the Lexus in the print ad is spinning its wheels and actually driving.
The Innovation Case: Static media has to become more interactive. There?s no doubt a wow factor in the idea that a boring old magazine ad can come to life. This is, in some ways, a form of augmented reality, which was quite popular with creative agencies for a while.
The PR Case: Who in their right mind is going to read a magazine, then bring it over to their iPads to do this? There?s a reason AR never really caught on with consumers as much as advertisers. It?s too much work for too little payoff. The campaign?s slick overview video is perfect for blogs and publications. Mashable wrote about the effort this week and wondered if it is ?the future of print advertising.?
Duke Medicine news -- Anti-cancer drug fights immune reaction in some infants with Pompe diseasePublic release date: 11-Oct-2012 [ | E-mail | Share ]
Contact: Sarah Avery sarah.avery@duke.edu 919-660-1306 Duke University Medical Center
DURHAM, N.C. Adding a third anti-cancer agent to a current drug cocktail appears to have contributed to dramatic improvement in three infants with the most severe form of Pompe disease -- a rare, often-fatal genetic disorder characterized by low or no production of an enzyme crucial to survival.
Duke researchers previously pioneered the development of the first effective treatment for Pompe disease via enzyme replacement therapy (ERT). ERT relies on a manufactured enzyme/protein to act as a substitute for the enzyme known to be lacking in patients with a particular disease. In Pompe disease, ERT has been found to reduce heart and muscle damage caused by the absence of the enzyme.
In the new study, appearing online in the Oct. 11, 2012, edition of the journal Genetics in Medicine, the Duke team added a new step to the therapeutic regimen to address complications suffered by a subset of infants with Pompe disease who are treated with ERT.
Some infants with Pompe disease who have certain combinations of genetic mutations develop a severe immune response to ERT. Very high levels of antibodies become directed against the enzyme and greatly reduce its therapeutic effect, leading to rapid clinical decline and death.
In a January 2012 publication in Genetics in Medicine, the researchers reported success in preventing the immune rejection in Pompe infants who were just beginning ERT. They treated them with a drug cocktail that included low doses of the cancer chemotherapy drugs rituximab and methotrexate, plus the immune booster gammaglobulin to prevent the immune response to the ERT.
The three cases described in the new paper had already received the ERT for a prolonged period of time and, despite initial improvements, declined rapidly as their bodies developed high levels of antibodies that blocked the effect of the enzyme replacement. In these youngsters, plasma cells, which are the ultimate source of antibody production, were left untouched by the immune-suppressing drug cocktails.
"These plasma cells form rapidly after exposure to ERT, and some of them are what we call long-lived plasma cells that survive for years, continuing to spew out antibodies," explained senior author Priya Kishnani, M.D., professor of Pediatrics and Medical Genetics at Duke.
After testing their ideas in mouse models of Pompe disease, the Duke researchers added a proteasome inhibitor called bortezomib to the regimen. Bortezomib, which is FDA-approved to treat multiple myeloma and mantle cell lymphoma, targets the plasma cells and inhibits the production of antibodies, reversing the established immune response.
In all three cases the antibodies decreased rapidly. Just as rapidly, each of the babies' conditions dramatically improved and the babies have continued to do well.
"I'm absolutely delighted, because to me this has become life-saving for these fragile babies," Kishnani said. "This is what I truly think is translational research, where you learn about a problem in patients, address it in an animal model and take it back into the patients to make a difference."
"We were encouraged with the positive results from preclinical studies using bortezomib. We quickly developed a clinical protocol using bortezomib for infantile Pompe patients that had failed conventional treatment. It was truly a satisfying experience," said first author Suhrad Banugaria, MBBS, postdoctoral associate in Pediatrics Medical Genetics at Duke.
Next, the group is working to develop treatments that more specifically target antigens eliciting immune responses to ERT. Kishnani and colleagues hope that such a targeted approach might minimize the impact on the immune system generally.
Kishnani said the insights her team has gained treating Pompe disease could be applied to other diseases in which an immune response has also been shown to reduce the impact of enzyme replacement therapy.
"We're already getting calls for other conditions such as mucopolysaccharidosis and Fabry disease, where physicians are facing the same issues: patients who have developed a significant antibody response and are not doing as well, or have started to show a clinical decline," Kishnani said.
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In addition to Kishnani and Banugaria, authors include Sean N. Prater, Duke Department of Pediatrics; Judeth K. McGann, Jonathan D. Feldman, and Jesse A. Tannenbaum of Kaiser Permanente, Santa Clara, Cal.; Carrie Bailey and David Viskochil of the University of Utah; Renuka Gera and Robert L. Conway of Michigan State University; Joyce A. Kobori of Kaiser Permanente, San Jose, Cal.; and Amy S. Rosenberg of the U.S. Food and Drug Administration, Bethesda, Md.
Kishnani reports receiving research support, honoraria and consulting fees from Genzyme, which markets an ERT for Pompe disease. Duke University and the inventors of the method of treatment and precursors of the cell lines used to generate the enzyme (rhGAA) used commercially have received royalties pursuant to the university's policy on inventions, patents, and technology transfer. This potential conflict has been resolved through monetization. Full dislosures of conflicts are listed in the manuscript.
Click on link for a conceptual diagram of the immune response: http://www.dukehealth.org/pompe-disease-graphic
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Duke Medicine news -- Anti-cancer drug fights immune reaction in some infants with Pompe diseasePublic release date: 11-Oct-2012 [ | E-mail | Share ]
Contact: Sarah Avery sarah.avery@duke.edu 919-660-1306 Duke University Medical Center
DURHAM, N.C. Adding a third anti-cancer agent to a current drug cocktail appears to have contributed to dramatic improvement in three infants with the most severe form of Pompe disease -- a rare, often-fatal genetic disorder characterized by low or no production of an enzyme crucial to survival.
Duke researchers previously pioneered the development of the first effective treatment for Pompe disease via enzyme replacement therapy (ERT). ERT relies on a manufactured enzyme/protein to act as a substitute for the enzyme known to be lacking in patients with a particular disease. In Pompe disease, ERT has been found to reduce heart and muscle damage caused by the absence of the enzyme.
In the new study, appearing online in the Oct. 11, 2012, edition of the journal Genetics in Medicine, the Duke team added a new step to the therapeutic regimen to address complications suffered by a subset of infants with Pompe disease who are treated with ERT.
Some infants with Pompe disease who have certain combinations of genetic mutations develop a severe immune response to ERT. Very high levels of antibodies become directed against the enzyme and greatly reduce its therapeutic effect, leading to rapid clinical decline and death.
In a January 2012 publication in Genetics in Medicine, the researchers reported success in preventing the immune rejection in Pompe infants who were just beginning ERT. They treated them with a drug cocktail that included low doses of the cancer chemotherapy drugs rituximab and methotrexate, plus the immune booster gammaglobulin to prevent the immune response to the ERT.
The three cases described in the new paper had already received the ERT for a prolonged period of time and, despite initial improvements, declined rapidly as their bodies developed high levels of antibodies that blocked the effect of the enzyme replacement. In these youngsters, plasma cells, which are the ultimate source of antibody production, were left untouched by the immune-suppressing drug cocktails.
"These plasma cells form rapidly after exposure to ERT, and some of them are what we call long-lived plasma cells that survive for years, continuing to spew out antibodies," explained senior author Priya Kishnani, M.D., professor of Pediatrics and Medical Genetics at Duke.
After testing their ideas in mouse models of Pompe disease, the Duke researchers added a proteasome inhibitor called bortezomib to the regimen. Bortezomib, which is FDA-approved to treat multiple myeloma and mantle cell lymphoma, targets the plasma cells and inhibits the production of antibodies, reversing the established immune response.
In all three cases the antibodies decreased rapidly. Just as rapidly, each of the babies' conditions dramatically improved and the babies have continued to do well.
"I'm absolutely delighted, because to me this has become life-saving for these fragile babies," Kishnani said. "This is what I truly think is translational research, where you learn about a problem in patients, address it in an animal model and take it back into the patients to make a difference."
"We were encouraged with the positive results from preclinical studies using bortezomib. We quickly developed a clinical protocol using bortezomib for infantile Pompe patients that had failed conventional treatment. It was truly a satisfying experience," said first author Suhrad Banugaria, MBBS, postdoctoral associate in Pediatrics Medical Genetics at Duke.
Next, the group is working to develop treatments that more specifically target antigens eliciting immune responses to ERT. Kishnani and colleagues hope that such a targeted approach might minimize the impact on the immune system generally.
Kishnani said the insights her team has gained treating Pompe disease could be applied to other diseases in which an immune response has also been shown to reduce the impact of enzyme replacement therapy.
"We're already getting calls for other conditions such as mucopolysaccharidosis and Fabry disease, where physicians are facing the same issues: patients who have developed a significant antibody response and are not doing as well, or have started to show a clinical decline," Kishnani said.
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In addition to Kishnani and Banugaria, authors include Sean N. Prater, Duke Department of Pediatrics; Judeth K. McGann, Jonathan D. Feldman, and Jesse A. Tannenbaum of Kaiser Permanente, Santa Clara, Cal.; Carrie Bailey and David Viskochil of the University of Utah; Renuka Gera and Robert L. Conway of Michigan State University; Joyce A. Kobori of Kaiser Permanente, San Jose, Cal.; and Amy S. Rosenberg of the U.S. Food and Drug Administration, Bethesda, Md.
Kishnani reports receiving research support, honoraria and consulting fees from Genzyme, which markets an ERT for Pompe disease. Duke University and the inventors of the method of treatment and precursors of the cell lines used to generate the enzyme (rhGAA) used commercially have received royalties pursuant to the university's policy on inventions, patents, and technology transfer. This potential conflict has been resolved through monetization. Full dislosures of conflicts are listed in the manuscript.
Click on link for a conceptual diagram of the immune response: http://www.dukehealth.org/pompe-disease-graphic
[ | E-mail | Share ]
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AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.
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I sat astride my banana seat bike in a parking lot and stared down a thirty foot strip of pavement. It was six inches wide and lined with rubber balls. I was nine years old and participating in a bicycle rodeo. The objective was to ride the entire length without hitting a single ball. The slightest bump would send them rolling.
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Public release date: 11-Oct-2012
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