Cost of Brand-Name Prescription Medicines Soaring

The price of brand-name prescription medicines is rising far faster than the inflation rate, while the price of generic drugs has plummeted, creating the largest gap so far between the two, according to a report published Wednesday by the pharmacy benefits manager Express Scripts.

The report tracked an index of commonly used drugs and found that the price of brand-name medicines increased more than 13 percent from September 2011 to this September, which it said was more than six times the overall price inflation of consumer goods. Generic drug prices dipped by nearly 22 percent.

The drop in the price of generics “represents low-hanging fruit for the country to save money on health care,” said Dr. Steve Miller, the chief medical officer of Express Scripts, which manages the drug benefits for employers and insurers and also runs a mail-order pharmacy.

The report was based on a random sample of six million Express Scripts members with prescription drug coverage.

The Pharmaceutical Research and Manufacturers of America, the trade group representing brand-name manufacturers, criticized the report, saying it was skewed by a handful of high-priced specialty drugs that are used by a small number of patients and overlooked the crucial role of major drug makers.

“Without the development of new medicines by innovator companies, there would be neither the new treatments essential to progress against diseases nor generic copies,” Josephine Martin, executive vice president of the group, said in a statement.

The report cited the growth of specialty drugs, which treat diseases like cancer and multiple sclerosis, as a major reason for the increase in spending on branded drugs. Spending on specialty medicines increased nearly 23 percent during the first three quarters of 2012, compared with the same period in 2011. All but one of the new medicines approved in the third quarter of this year were specialty drugs, the report found, and many of them were approved to treat advanced cancers only when other drugs had failed.

Stephen W. Schondelmeyer, a professor of pharmaceutical economics at the University of Minnesota, said the potential benefits of many new drugs did not always match the lofty price tags. “Increasingly it’s going to be difficult for drug-benefit programs to make decisions about coverage and payment and which drugs to include,” said Mr. Schondelmeyer, who conducts a similar price report for AARP. He also helps manage the drug benefit program for the University of Minnesota.

“We’re going to be faced with the issue that any drug at any price will not be sustainable.”

Spending on traditional medicines — which treat common ailments like high cholesterol and blood pressure — actually declined by 0.6 percent during the period, the report found. That decline was mainly because of the patent expiration of several blockbuster drugs, like Lipitor and Plavix, which opened the market for generic competitors. But even as the entry of generic alternatives pushed down spending, drug companies continued to raise prices on their branded products, in part to squeeze as much revenue as possible out of an ever-shrinking portfolio, Dr. Miller said.

Drug makers are also being pushed by companies like Express Scripts and health insurers, which are increasingly looking for ways to cut costs, said C. Anthony Butler, a pharmaceuticals analyst at Barclays. “I think they’re pricing where they can but what they keep telling me is they’re under significant pressure” to keep prices low, he said.

Express Scripts earns higher profits from greater use of generic medicines than brand name drugs sold through their mail-order pharmacy, Mr. Butler said. “There’s no question that they would love for everybody to be on a generic,” he said.

Dr. Miller acknowledged that was true but said that ultimately, everyone wins. “When we save people money, that’s when we make money,” he said. “We don’t shy away from that.”

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French court clears Continental in Concorde crash

French appeals court on Thursday absolved Continental Airlines of blame for a 2000 Concorde crash that killed 113 people and cleared a mechanic at the U.S. airline of the charge of involuntary manslaughter.

The verdict comes over a decade after the accident helped to spell the end of the supersonic airliner. A previous court ruled that a small metal strip that fell onto the runway from a Continental aircraft just before the Concorde took off from Paris, caused the crash.

Continental was originally fined 200,000 euros and ordered to pay the Concorde's operator, Air France, a million euros in damages. Continental appealed the verdict which it described as unfair and absurd.

Welder John Taylor was cleared of a 15-month suspended prison sentence for having gone against industry norms and used titanium to forge the piece that dropped off the plane.

Continental, now part of United Continental Holdings , had been ordered under the original ruling to pay 70 percent of any damages payable to families of victims. Airbus parent EADS would have to pay the other 30 percent.

The crash sped up the demise of the droop-nosed Concorde - the fastest commercial airliner in history and a symbol of Franco-British co-operation - as safety concerns coupled with an economic downturn after 9/11 drove away its wealthy customers.

The Air France Concorde, carrying mostly German tourists bound for a Caribbean cruise, was taking off from Paris on July 25, 2000 when an engine caught fire. Trailing a plume of flames, it crashed into a hotel near Charles de Gaulle airport. All 109 passengers and four people on the ground died.

After modifications, the plane returned to service but its operators, Air France and British Airways, retired it in 2003, citing high operating costs and a drop in demand.
 

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Groupon CEO Mason open to stepping down

Groupon CEO Andrew Mason walks outside the Nasdaq after the company debuts in November 2011. (Brendan McDermid/Reuters / November 28, 2012)

Reuters

11:31 a.m. CST, November 28, 2012

Groupon Inc. CEO Andrew Mason, under fire for a plunging share price and tapering growth, said on Wednesday he would agree to step down if needed, as the struggling company's board prepared to debate on Thursday whether he remains the right leader.

Groupon has shed four-fifths of its value since its public trading debut as an investor darling during last year's consumer dotcom IPO boom. Wall Street has grown uneasy about the viability of its business as fever for daily deals has cooled among consumers and merchants, hurting its growth rate.

Mason, responding to reports that the board of directors will discuss his performance during a regular Thursday meeting, said it would be "weird" if they did not.

"It would be more noteworthy if the board wasn't discussing whether I'm the right guy for the job," Mason said in an interview from a Business Insider conference.

"If I ever thought I wasn't the right person for the job, I'd be the first person to fire myself."

Europe has been a particular problem for Groupon, partly because the sovereign debt crisis has sapped demand for higher-priced deals. Groupon was also offering steeper discounts, turning off some European merchants.

Adding to its difficulties, the U.S. Securities and Exchange Commission is looking into Groupon's accounting and disclosures, areas that raised questions among some during its IPO.

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German lawmakers condemn Google campaign against copyright law

BERLIN (Reuters) – Senior German politicians have denounced as propaganda a campaign by Google to mobilize public opinion against proposed legislation to let publishers charge search engines for displaying newspaper articles.

Internet lobbyists say they are worried the German law will set a precedent for other countries such as France and Italy that have shown an interest in having Google pay publishers for the right to show their news snippets in its search results.

Lawmakers in Berlin will debate the bill in the Bundestag (lower house) on Thursday. Google says the law would make it harder for users to retrieve information via the Internet.

Google launched its campaign against the bill on Tuesday with advertisements in German newspapers and a web information site called “Defend your web”.

“Such a law would hit every Internet user in Germany,” Stefan Tweraser, country manager for Google Germany, said in a statement. “An ancillary copyright means less information for consumers and higher costs for companies.”

The campaign has caused outrage among some members of German Chancellor Angela Merkel’s center-right coalition.

“The campaign initiated by Google is cheap propaganda,” said conservative lawmakers Guenter Krings and Ansgar Heveling.

“Under the guise of a supposed project for the freedom of the Internet, an attempt is being made to coopt its users for its own lobbying,” the two said in a statement.

Supporters of the law argue that newspaper publishers should be able to benefit from advertising revenues earned by search engines using their content.

Under the plans, publishers would get a bigger say over how their articles are used on the Internet and could charge search engines for showing articles or extracts.

German Justice Minister Sabine Leutheusser-Schnarrenberger, a member of the Free Democrats (FDP) who share power in Merkel’s government, said she was astonished that Google was trying to monopolize opinion-making. She is responsible for the law.

“PANIC MONGERING”

Germany’s newspaper industry, suffering from economic slowdown and keen to get its hands on any revenues it can, backs the plans and railed against Google’s campaign.

“The panic mongering from Google has no justification,” Germany’s BDZV newspaper association said in a statement.

“The argument from search engine companies that Internet searching and retrieval will be made more difficult is not serious. Private use, reading, following links and quoting will be possible, just as before.”

Internet lobbyists in Brussels fear the European Commission is sympathetic to publisher demands for a piece of Google’s profits online. Recent statements, they say, are proof.

“Consumers are not the only ones facing difficulties,” Michel Barnier, the EU’s internal market commissioner, said in a speech on November 7. “Think of newspaper publishers who see the content they produce being used by others to attract consumers on the net and generate advertising revenues.”

French newspapers and magazines want Google to pay them for linking to their articles on Google. The French government has named a mediator to negotiate with the press and Google to try to get a deal by the end of the year.

If no deal emerges, President Francois Hollande’s government will ask parliament to draft a law modifying copyright laws to protect the press from appropriation of its content online, according to a letter signed by two ministers on November 28.

(Additional reporting by Harro ten Wolde in Frankfurt, Claire Davenbport in Brussels and Leila Abboud in Paris; Writing by Madeline Chambers, Editing by Gareth Jones and)

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Thousands celebrate Hobbit premiere in New Zealand

WELLINGTON (Reuters) – Tens of thousands of people packed New Zealand’s capital city, clambering on roofs and hanging onto lamp posts on Wednesday to get a glimpse of the stars at the red carpet world premiere of the film “The Hobbit: an Unexpected Journey”.

Wellington, where director Peter Jackson and much of the post production is based, renamed itself “the Middle of Middle Earth“, and fans with prominent Hobbit ears, medieval style costumes, and wizard hats had camped out the night before to claim prized spaces along the 500 meter (550 yards) red carpet.

Jackson, a one time newspaper printer and the maker of the Oscar winning “Lord of the Rings” trilogy more than a decade ago, was cheered along the walk, stopping to talk to fans, sign autographs and pose for photos.

The Hobbit trilogy is set 60 years before the Rings movies, but Jackson said it has benefited from being made after the conclusion of the J.R.R. Tolkien fantasy saga.

“I’m glad that we established the style and the look of Middle Earth by adapting Lord of the Rings before we did the Hobbit,” Jackson told Reuters from the red carpet.

Jackson, a hometown hero in Wellington, said the production had been on a “difficult journey”, alluding to Warner Brothers’ financial problems, and a later labor dispute with unions.

“Fate meant for us to be here,” he told an ecstatic crowd, which hailed him as a film genius, but also a down to earth local boy.

“I came here to see the stars but also Peter (Jackson)…I loved the Lord of the Rings and that made me want to be here, without him none of it would be here,” said teenage student Samantha Cooper.

OLD FRIENDS

The cast was no less enthusiastic about the Hobbit, especially those who had starred in the Lord of the Rings trilogy.

British actor Andy Serkis, who plays the creature Gollum with a distinctive throaty whisper, said picking up the character after a near-ten year break was like putting on a familiar skin.

“I was reminded on a daily basis with Gollum (that) he’s truly never left me,” he said.

Most of the film’s stars attended the premiere, including British actor Martin Freeman, who plays the Hobbit Bilbo Baggins, Andy Serkis, Hugo Weaving, Cate Blanchett, and Elijah Wood. Ian McKellen, who plays the wizard Gandalf, was absent.

Freeman, known for his roles in the comedy The Office and Sherlock Holmes, said he looked for a different, lighter, slightly pompous Baggins from the older, wiser character played by Ian Holm in the Rings movies.

“Between us – Peter (Jackson) and me — we hashed out another version of Bilbo. There’ll be others, but our version is this one and I hope people like it,” he said.

The production was at the center of several controversies, including a dispute with unions in 2010 over labor contracts that nearly sent the filming overseas and resulted in the government stepping in to change employment laws.

The only sour note at the premiere came when animal rights activists held up posters saying “Middle Earth unexpected cruelty” and “3 horses died for this film”, after claims last week that more than 20 animals died during the making of the film.

Event organizers tried to block out the protesters’ posters with large Hobbit film billboards. Jackson has said some animals died on a farm where they were housed, but none had been hurt during filming.

The movies have been filmed in 3D and at 48 frames per second (fps), compared with the standard 24 fps, which Jackson has likened to the quality leap to compact discs from vinyl records.

The second film “The Hobbit: The Desolation of Smaug” will be released in December next year, with the third “The Hobbit: There and Back Again” due in mid-July 2014.

(Editing by Elaine Lies)

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F.D.A. May Tap Experts on Energy Drinks

The Food and Drug Administration said in a letter released on Tuesday that it was likely to seek advice from outside experts to help determine whether energy drinks posed particular risks to teenagers or people with underlying health problems.

The letter appears to signal a change in the agency’s approach to the drinks, which contain high levels of caffeine.

Previously, F.D.A. officials have said that they were investigating possible risks posed by popular products like 5-Hour Energy, Monster Energy and Red Bull. But an agency spokeswoman, Shelly Burgess, said the new letter was the first time that the F.D.A. had said it might turn to outside experts.

The F.D.A. letter, which was released Tuesday by Senator Richard J. Durbin of Illinois and Senator Richard Blumenthal of Connecticut, follows disclosures that the agency received reports of 18 deaths and over 150 injuries that mentioned the possible involvement of energy drinks.

The filing of such reports with the F.D.A. does not prove that a product was responsible for a death or an injury. Energy drink makers have said their products are safe and were not responsible for the health problems.

The officials said a review of the drinks might be “greatly enhanced by also engaging specialized expertise” from an outside group, like the Institute of Medicine, which is part of the National Academy of Sciences.

Industry analysts said the letter indicated that the F.D.A. did not plan any immediate actions on energy drinks, an interpretation that set off a rally on Tuesday in the stock of Monster Beverage, the producer of Monster Energy. Company shares closed at $51.97, up over 13 percent. Any regulatory outcome is likely to be “benign,” Judy Hong, an analyst at Goldman Sachs, said in a note to investors, according to Bloomberg News.

In Canada, however, the use of an outside panel led to limits on caffeine levels in energy drinks.

In their letter, F.D.A. officials indicated that an outside review would focus on the possible risks posed by high levels of caffeine, a stimulant, to certain groups. They reiterated that daily consumption of significant levels of caffeine, which is found in products like coffee and tea, is safe.

“Areas of particular focus would include such matters as the vulnerability of certain populations to stimulants and the incidence and consequence of excessive consumption” of energy drinks, especially by young people, F.D.A. officials wrote.

In Canada, an expert panel made several recommendations, including arguing that such beverages be labeled “stimulant drug-containing drinks.”

Health Canada, that country’s counterpart to the F.D.A., did not adopt many of the group’s recommendations, but it has put in place new rules limiting caffeine levels in cans of energy drinks to 180 milligrams.

Some larger-size cans of energy drinks sold in the United States, like the 24-ounce can of Monster Energy and the 20-ounce can of Red Bull, have caffeine levels above that limit.

An eight-ounce cup of coffee, depending on how it is made, can contain from 100 to 150 milligrams of caffeine.

In the new letter, F.D.A. officials also said that studies that had examined other ingredients, like taurine, that are often used in energy drinks had determined those substances were safe. The agency also said that a survey suggested that energy drinks constitute a small portion of the caffeine consumed in this country, even by teenagers.

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Grim forecast for U.S., global recovery

WASHINGTON — In a grim new forecast, a leading international economic group sharply cut its outlook for U.S. and global growth next year and warned that the debt crisis in Europe and fiscal policy risks in America could plunge the world back into recession.

As it stands now, the industrialized world is looking at a muted and uneven recovery over the next two years, according to the Organization for Economic Cooperation and Development.

The Paris-based OECD projected gross domestic product across its 34 member nations — which include the U.S., Japan and the 17-nation Eurozone — to grow a sluggish 1.4% next year. That is down from 2.2% that the group had forecasted six months earlier.

Growth prospects in the U.S. also were slashed for next year. Experts at the OECD now see inflation-adjusted GDP, the broadest measure of economic activity, rising 2% next year in the U.S., roughly equivalent to this year and down from its earlier forecast of an increase of 2.6%.

The new projections are all the more sobering in that they are based on assumptions that Europe's debt crisis won't get much worse and that the U.S. won't go over the so-called fiscal cliff — a combination of more than $500 billion in automatic tax hikes and federal spending cuts slated to begin at the start of next year.

Quiz: How much do you know about the 'fiscal cliff'?

"If key adverse risks cannot be averted, and especially if the Eurozone crisis were to intensify significantly, the likely outcome would be considerably weaker, potentially plunging the global economy into deep recession and deflation, with large additional rises in unemployment," the OECD said.

The report, released Tuesday, is on the pessimistic side.

Although economists widely agree on the recession risks in the event that the U.S. isn't able to solve the fiscal impasse, a number of experts now say that the U.S. and global economies could see considerably stronger growth next year if Washington can reach agreement on tax and spending policies that avoid a big fiscal contraction in 2013.

"The economy in the U.S. is really poised to grow," said Bernard Baumohl, chief global economist at the Economic Outlook Group, noting that GDP growth in the U.S. could surge to a solid 3.5% or higher next year if the budget issues are resolved.

The latest forecast from the Federal Reserve, compiled in mid-September, sees U.S. GDP increasing 2.5% to 3% next year.

Baumohl's reasons for greater optimism include a recovering housing market, improving job growth and healthier personal finances, all of which should help drive stronger consumer spending.

Total consumer debt, which has fallen for four years, dropped by $74 billion to $11.31 trillion in the third quarter from the previous quarter, and it is now down $1.37 trillion from the peak in September 2008, according to a report Tuesday from the New York Fed.

Reflecting these trends, the Conference Board said Tuesday that its latest survey showed consumer confidence at its highest level since early 2008, results similar to a survey by the University of Michigan.

American business sentiments, however, have been more cautious of late, and many companies have held back on making investments in recent months. But banks are generally in good shape, and big companies are sitting on mountains of cash and are expected to ramp up investments once the fiscal and tax pictures become clearer.

The OECD report nodded to these factors, but noted that the global recovery slowed markedly over the last year amid faltering confidence and weakening world trade, in part because of problems in the Eurozone, which contributed to an unexpectedly strong slowdown in developing countries such as China.

The 17-nation Eurozone will probably remain in recession well into next year, the OECD said.

Meanwhile, Japan, the world's third-largest economy, has fallen back into a downturn after a growth spurt last year aided by massive reconstruction spending following the earthquake and tsunami in March 2011. The Japanese economy is expected to move at a lumbering pace over the next two years.

The outlook for China, Brazil and India — three of the biggest developing economies, none of which is a member of the OECD — looks comparatively brighter:  Growth will probably accelerate next year and in 2014, with China, the world's second-largest economy, again leading the pack.

The OECD forecast sees China's GDP expanding 8.5% next year and nearly 9% in 2014 after slowing this year to about 7.5%.

Although far from immune from the troubles in the U.S. and Europe, which still account for much of the global demand for goods, China and other major emerging economies have more wherewithal to boost growth than their more-indebted developed counterparts by ramping up government spending and lowering interest rates.

The report notes that spending cuts throughout OECD member countries have taken a toll on economic growth, particularly in the Eurozone, where GDP growth for next year was slashed to -0.1% from a positive rate of 0.9%.

Many developed countries are now struggling with financial and economic challenges related to an aging population, large public debts and high unemployment.

Assuming Europe's debt crisis stabilizes, the Eurozone is forecast to recover in 2014. For OECD countries overall, GDP growth is projected to pick up in 2014 to 2.3%.

The U.S. economy is expected to outperform most other OECD nations in 2014, with its GDP stepping up to a more sturdy growth of 2.8%. That compares with the Fed's forecast of 3% to 3.8% growth in 2014.

Either way, U.S. economic growth isn't likely to come close to keeping up with the rapid advance of developing countries, notably China.

Last year, the U.S. accounted for 23% of the global economy, with the Eurozone and China tied for second, each with a 17% share each.

But by 2030, the OECD estimates, China's share of the global economy will rise to 28%, while the U.S. will slip to No. 2 with 18% of world GDP, and the Eurozone's share will fall to 12%.

don.lee@latimes.com

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Vaughn gets 4 life terms for killing wife, 3 children

Christopher Vaughn was sentenced to four life terms this morning for fatally shooting his wife and three children after pulling off an expressway in 2007.

Vaughn looked over his shoulder at his family as he was led away after being sentenced by Judge Daniel Rozak for the murders of his wife Kimberly and their three children, Abigayle, 12, Cassandra, 11 and Blake, 8.

Kimberly's family hugged and shook hands with investigators in the courtroom.

Earlier, Kimberly twin sister Jennifer Ledbetter told the judge that "our hearts ache with the knowledge that they were priceless to everyone but the one man who should have loved them more than their own life."

Vaughn seemed to wipe his eyes several times as Ledbetter read her statement.

Also addressing the court was Kimberly's mother, Susan Phillips. In a matter-of-fact tone, she called Vaughn "a selfish coward" who had "destroy(ed) the very best thing that he had, a loving wife and three amazing children" and caused incredible pain for the surviving family.

Vaughn murdered his wife and kids, prosecutors say, because he saw them as obstacles to his dream of a new life in Canada. He posted wistful Internet messages about building a cabin and settling in the Yukon cut off from the world.

According to prosecutors, Vaughn woke his family on the day of the killings promising a surprise trip to a water park. But shortly after 5 a.m., he pulled off the road and shot them. Each child was shot once in the chest and head while buckled in the back seat of the family SUV.

Abigayle was found holding a stuffed animal. Blake's wounds indicated he had raised his arm to shield himself.

At the trial, defense attorneys told jurors that Vaughn's wife was to blame, saying she was suicidal over marital strife. They suggested she shot her husband in the wrist and leg, then killed the children and herself.

But prosecutors asked jurors whether it seemed reasonable that a woman who disliked guns could have shot her husband twice, only grazing him each time, but fatally shot each of her children with a marksman's precision.

They contended that Christopher Vaughn shot himself to make it look like his wife carried out the attack, and told jurors that Vaughn showed little emotion after the shootings and was more interested in his damaged clothing than the fate of his family.

Vaughn had been scheduled to be sentenced Monday. But Rozak halted the sentencing so he could review transcripts and television broadcast reports before ruling on a motion for a new trial from the defense, which argued that publicity from another high-level murder trial had prejudiced the jurors.

Vaughn's September trial overlapped with the trial of Drew Peterson, the former Bolingbrook police sergeant convicted of killing his third wife.  Vaughn's attorney, George Lenard, argued that part of the reason his client didn't get a fair trial was because the press conferences held by Peterson's lawyers outside the courthouse damaged his own credibility as a defense attorney.

Rozak denied the motion this morning, saying he had admonished jurors to avoid all news coverage during the trial.

Also, Rozak said any comparisons he heard between the two defense teams characterized Lenard as "the second coming of Clarence Darrow while the others were like a rerun of Mo Howard in 'Disorder in the Court.' "

Lenard, who cited 51 grounds for a new trial, began his more than two-hour oral argument Monday by taking some shots at former Peterson co-counsel Joel Brodsky.

Lenard criticized a news conference held by Peterson's new defense team that he said seemed to mock the disappearance of Peterson's fourth wife, Stacy. Prosecutors believe Peterson killed Stacy, but he has not been charged. He was tried this summer for the 2004 drowning of his third wife, Kathleen Savio.

"That gave criminal defense attorneys — all of us — a black eye," Lenard told the judge, saying jurors may have been so disgusted by this "show" that they were unfairly prejudiced against Vaughn's defense team.

"I think they need to apologize about what they said out there," Lenard later told reporters outside the courthouse.

Prosecutors called the argument "unbelievable," and Peterson attorney Joe Lopez tweeted it was "hilarious to blame us for his loss."

"It's unbelievable that the Drew Peterson case would find itself in the Christopher Vaughn case," Assistant State's Attorney Mike Fitzgerald said.

"If they thought the Drew Peterson trial was going to be an influence, why didn't they do something about it at the time?"

Lenard said he never expected media coverage of the two trials to overlap. He also cited as grounds for a new trial closing arguments that he said were a "personal attack" against him and the speed with which jurors returned a verdict.

Fitzgerald said jurors might have returned a verdict in less than an hour because they found the evidence of Vaughn's guilt "overwhelming."

Lenard said that in his 28 years of practicing law, he's never before seen jurors return a verdict so quickly without asking to review evidence.

"I don't know exactly what it is that they were thinking, but 45 minutes and not asking for any exhibits, not wanting to hear any testimony, that's extremely rare. I've never had that situation before and that's odd."

sschmadeke@tribune.com

Twitter: @ChicagoBreaking

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Disney Channel to debut ‘Sofia the First’ Jan. 11

NEW YORK (AP) — Disney says its animated children‘s series “Sofia the First” will premiere Jan. 11 on the Disney Channel and Disney Junior networks.

Created for kids ages 2 to 7, “Sofia the First” is about a young girl who becomes a princess and learns that honesty, loyalty and compassion are what makes a person royal.

Sofia is voiced by “Modern Family” actress Ariel Winter, and her mother is played by “Grey’s Anatomy” star Sara Ramirez.

Last week’s premiere of the “Sofia the First” animated movie drew a total audience of more than 5 million viewers. It was the year’s top-rated cable TV telecast among kids ages 2 to 5.

In the series’ debut episode, Sofia strives to become the first princess to earn a spot on her school’s flying derby team.

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Imaging Shows Progressive Damage by Parkinson’s

For the first time, researchers at the Massachusetts Institute of Technology report, brain imaging has been able to show in living patients the progressive damage Parkinson’s disease causes to two small structures deep in the brain.

The new technique confirms some ideas about the overall progress of the disease in the brain. But the effects of Parkinson’s vary in patients, the researchers said, and in the future, the refinement in imaging may help doctors monitor how the disease is affecting different people and adjust treatment accordingly.

The outward symptoms and progress of Parkinson’s disease — tremors, stiffness, weakness — have been well known since James Parkinson first described them in 1817. But its progress in the brain has been harder to document.

Some of the structures affected by the disease have been buried too deep to see clearly even with advances in brain imaging. An important recent hypothesis about how the disease progresses was based on the examinations of brains of patients who had died.

Now, a group of scientists at M.I.T. and Massachusetts General Hospital report that they have worked out a way to combine four different sorts of M.R.I. to get clear pictures of damage to two brain structures in people living with Parkinson’s. In doing so, they have added support to one part of the recent hypothesis, which is that the disease first strikes an area involved in movement and later progresses to a higher part of the brain more involved in memory and attention.

Suzanne Corkin, a professor emerita of behavioral neuroscience at M.I.T. and the senior author on the paper published online Monday in The Archives of Neurology, said that this progression was part of the hypothesis put forward in 2003 by Heiko Braak, a German neuroscientist, based on autopsies.

But, she said, because of the limits of brain imaging, “nobody could test this in living patients.”

David A. Ziegler, who was at M.I.T. when the research was done, and is now a postdoctoral researcher at the University of California, San Francisco, said that the study, of 29 patients with Parkinson’s and 27 healthy patients of roughly the same age, showed that the peanut-sized substantia nigra lost volume first, and another structure called the basal forebrain, involved in memory and attention, was struck later.

Glenda Halliday, a neuroscientist at Neuroscience Research Australia and the University of New South Wales, who was not involved in the study, said the paper confirmed “the progression of degeneration in two important affected brain regions in people with Parkinson’s.”

Dr. Corkin, Dr. Ziegler and their colleagues developed a way to use four different varieties of M.R.I. — each using different settings on the same machine — to come up with four different images that could be used to form one image that showed structures deep in the brain like the substantia nigra, long known to be important in Parkinson’s.

The disease kills brain cells, shrinking the parts of the brain that it affects, and the comparative study showed that the reduction in size of the substantia nigra showed up in early stage Parkinson’s patients, compared with a healthy group.

The reduction in size in the basal forebrain, compared with the healthy group, did not show up in the patients in the early stage, but was clear in patients in the later stage.

“This is a project we’ve been working on in our lab for years,” she said. A next step, already in progress, is to correlate damage to specific brain structures with symptoms.

Parkinson’s, she said, is a disease that shows the same broad outlines of development in most patients, but with considerable variation. Dementia may arrive early or may not appear. The M.R.I. technique described in the paper, she said, might help tease out what is going on in the brain in subgroups of Parkinson’s patients that show different symptoms and could influence treatment.

One important difference between the two brain structures is that damage to the substantia nigra decreases production of the neurotransmitter dopamine, while a smaller basal forebrain would reduce the production of a different chemical, acetylcholine.

The research is just one step, Dr. Ziegler said. One of the “big outstanding questions,” he said, is whether all patients will eventually get dementia.

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