Sergey Brin, the 38-year-old co-founder of Google Inc., is making strides in his quest to find a cure for Parkinson’s, a progressive disease his DNA and family history suggest may afflict him as early as 10 years from now.
The advances are encouraging Pfizer Inc. and GlaxoSmithKline Plc to pursue a new class of medicines that may become the first to slow the progress of Parkinson’s disease in a unique collaboration that Brin is funding.
Brin, who began donating to Parkinson’s research in 2005, accelerated that giving after he learned in 2008 he has a flawed gene that presents him with a 50 percent chance of getting the disease by age 70. So far Brin has donated $132 million, mostly through the Michael J. Fox Foundation for Parkinson’s Research, to help create a DNA database of 7,000 patients and to support work on the first targeted treatments that aim at the genetic causes of the movement disorder.
“If I felt it was guaranteed to cure Parkinson’s disease a check for a billion dollars would be the easiest one I have written,” he said in an interview. “Pretty much everybody in the world has or will have some serious condition. How much is it worth to you to have that condition be potentially curable?”
Among the recipients of Brin’s largess is the company his wife, Anne Wojcicki, started to create a database of genetic information and which found that Brin had the Parkinson’s gene.
Depression and Dementia
While existing Parkinson’s medicines help with symptoms, they don’t slow the progression of the disease, in which brain cells involved in coordinating movement die off, leading to tremors, stiffness, slowness, difficulty speaking, depression and dementia.
Parkinson’s afflicts about 1 million people in the U.S., and 1 in 100 people over age 60. It was first described in an 1817 essay by the British surgeon James Parkinson about six patients with a “shaking palsy.” A 2009 study estimated the disease costs Americans $10.8 billion a year, including $6.22 billion in medical costs such as drug treatments and nursing home care, and $4.56 billion more in lost wages and other indirect costs.
“As of today there’s nothing specific that Sergey can do about it, but that doesn’t mean he can’t try to drive change, which we’re doing,” said Wojcicki, co-founder and chief executive of closely held personal genomics company 23andMe Inc., in an interview.
Brin’s mother, Eugenia, a former computer scientist at NASA, first began to suffer symptoms in 1997 at age 49. A genetic test developed by 23andMe showed Brin and his mother have the Parkinson’s gene. Brin’s funding efforts through the Fox Foundation are studying specific blocking mechanisms that may offer the first real treatment to slow the disease.
“I was very surprised” to get the result in 2008, Brin said. “I wasn’t alarmed. I felt empowered. I felt I could invest in the research,” said Brin, who has a net worth of about $19 billion.
Brin and Wojcicki “have been hugely helpful,” said Michael J. Fox, the actor who started his eponymous foundation in 2000, nine years after developing Parkinson’s disease.
“People of their profile, who are smart and savvy, when they get involved in such a big way it encourages scientists to take it seriously and it encourages industry to take it seriously,” Fox said in a telephone interview.
‘EBay for Research’
Wojcicki said the company she founded in 2006 is aiming to create an “EBay for research” that would speed discoveries in difficult diseases by connecting doctors and researchers to unprecedented amounts of gene data.
“If Sergey is in the database, I just don’t want 23andMe to have access to the data, I want every smart LRRK2 researcher to have access,” she said in an interview referring to the Parkinson’s-linked gene mutation Brin carries known as LRRK2.
Better sharing of data from millions of patients would speed research into treatments for everything from brain diseases to heart disease to cancer, Brin said.
“It could be transformational,” he said.
People with Parkinson’s are short on dopamine, a natural substance in the brain essential to normal nerve activity. Researchers have identified 6 rare Parkinson’s genes, including the LRRK2 mutation first discovered in 2004.
Since then, Brin and Wojcicki have funneled $124.9 million to the Fox Foundation, making them the organization’s biggest funder. Starting in 2009, Brin has also funded researchers at 23andMe to create a DNA database, the largest gene study of Parkinson’s patients in the world, according to the Mountain View, California-based company. He has agreed to underwrite genotyping for the first 10,000 people who join. Brin has also contributed $7 million to the Parkinson’s Institute and Clinical Center.
Brin started donating in earnest to the Fox Foundation after the group’s co-founder Deborah W. Brooks, a former vice president at Goldman Sachs Group Inc., heard in 2004 that his mother had the disease. She called Intel Corp. co-Founder Andrew Grove, a Parkinson’s sufferer and foundation donor. Grove set up a dinner with Brin and Brooks at the Stanford Park Hotel in Menlo Park, California, near Stanford University, she said.
At the dinner, Brin grilled Brooks on the state of Parkinson’s disease research. The meeting led to a partnership.
The Fox Foundation has helped 23andMe get patients for its database. Parkinson’s is “uniquely suited” to Web-based research, since patients often have difficulty getting to the doctor yet are able to report symptoms online and send in a saliva sample, said Nick Eriksson, a 23andMe biostatistician.
The data effort has started to yield results. Researchers at 23andMe last year said they had spotted a gene that may protect against the harmful effects of LRRK2, explaining why some people with the mutation never get the disease.
Scientists at Stanford University reported in March 2011 they had transformed skin cells donated from Eugenia Brin into brain cells with Parkinson’s symptoms. These cells, and similar cell lines from other patients, will let researchers duplicate the disease in the lab to test for potential drugs, said William Langston, who treats Brin’s mother and runs the Parkinson’s Institute and Clinical Center based in Sunnyvale, California.
John Hardy, a brain genetics researcher at University College London whose department has received Fox Foundation funding, calls the LRRK2 gene “almost a dream target” for companies searching for Parkinson’s drugs. The gene creates a protein that can be blocked with chemicals similar to certain cancer drugs already on the market, giving researchers a head start on finding a targeted drug.
The obstacles toward creating drugs that slow Parkinson’s are daunting. Researchers know little about how LRRK2 weakens brain cells, and by the time the disease is diagnosed the majority of dopamine-producing neurons may already be dead.
Researchers are only beginning to develop tests to spot the disease earlier, when it might still be possible to preserve the brain cells.
Ted Dawson, a neuroscientist at Johns Hopkins University in Baltimore, is maintaining his optimism.
While human trials are still several years off, “it is just going to be a matter of time to move these forward,” said Dawson, who showed in 2010 that compounds used against LRRK2 could block brain cell death in mice.
The mutation creates a defective protein that kills brain cells within 24 to 48 hours in the test tube, according to research from Dawson. Blocking the protein might stop or slow progress of the disease.
Places to Start
The new findings are giving drug and biotechnology companies starting points for personalized drugs that will first be tested in subsets of patients with the bad genes, said Owen Ross, a brain genetics researcher at the Mayo Clinic in Jacksonville, Florida.
“The momentum has been incredible,” he said.
While LRRK2 is directly responsible for 1 or 2 percent of Parkinson’s cases, the research “could have implications for the vast majority of Parkinson’s patients,” Ross said.
Researchers at Eli Lilly & Co. began working on drugs to block LRRK2, “literally the day after the first papers got published,” said Kalpana Merchant, chief scientific officer for translational science for the Indianapolis-based drugmaker.
“Now we have a gene tied to the disease where we know how to target it with drug-like molecules,” she said.
When Brin realized he had DNA that suggested he, like his mother, could eventually suffer from the disease he and Wojcicki determined they wanted to do something big.
When the Fox Foundation’s Brooks was contacted, she visited Brin at Google’s headquarters with a suggestion: Why not create a Manhattan Project to devise drugs against LRRK2?
Brin signed on with a $20 million donation, $15 million designated for LRRK2, and has been the main sponsor on the Fox Foundation’s LRRK2 effort since. Last year, Brin and Wojcicki pledged to match any further new donations of as much as $50 million, with half the money directly targeted for research into LRRK2.
The Fox Foundation directly funds Pfizer and GlaxoSmithKline to do LRRK2 drug research. A larger group of industry advisers, including scientists from Pfizer, Glaxo, Lilly and Elan Corp., holds regular calls to discuss roadblocks toward making LRRK2 drugs that researchers could help solve.
The collaboration helps share the risk of drug discovery and gives Pfizer access to a worldwide network of experts on LRRK2, said Michael Ehlers, chief scientific officer for Pfizer’s neuroscience research, in a telephone interview.
Maybe for Sergey
“It is a natural kind of alliance” that will become more common, he said. Pfizer could have a LRRK2 medicine in human trials in two to three years, he said.
Money from the foundation in 2009 allowed Glaxo to hire contract chemists to craft drugs against LRRK2, said Alastair Reith, the research manager who leads the project. Without the funding, Glaxo’s work might have languished, as drug companies “are paring back quite drastically” in brain diseases, he said.
Parkinson’s, which afflicts fewer people than Alzheimer’s, “isn’t high in the pecking order,” he said by telephone.
Eugenia Brin, now retired and living in Los Altos Hills, California, is philosophical about the chances for a cure.
“I do hope they find a drug,” she said in a telephone interview. “It may be too late for me -- but maybe in time for Sergey.”