Brain barrier breached in push to deliver Alzheimer's drug

Back to TopCommentsE-mailPrintBookmark and Share

Scientists with Roche Holding AG, the parent company of Indianapolis-based Roche Diagnostics Corp., may have found a way to overcome a blood barrier that keeps drugs from directly entering the brain, potentially opening new pathways to attack Alzheimer’s disease.

The technique, tested in animals, makes use of a receptor that carries iron molecules across the barrier of blood, fluid and membranes that keeps bacteria and other substances, such as medicines, out of the brain, said Ryan Watts, a researcher at Roche’s Genentech unit in San Francisco. The scientists configured a protein called an antibody to hitch a ride on the receptor, he said.

Alzheimer’s impairs mental function in 18 million people globally, the World Health Organization says. Numerous drugmakers, including Indianapolis-based Eli Lilly and Co., are struggling to find a treatment.

Namenda, from New York-based Forest Laboratories Inc., and Aricept, made by Pfizer Inc. of New York and Tokyo-based Eisai Co., address symptoms without slowing or curing the disease. Efforts to alter its course with drugs have failed partly because of the barrier.

“It’s brilliant,” said Robert Vassar, a professor of cell and molecular biology at Northwestern University Medical School in Chicago. “They hijacked a mechanism that is a normal part of the blood-brain barrier.”

Roche, based in Basel, Switzerland, is Europe’s largest drugmaker by sales. The approach described Wednesday in the journal Science Translational Medicine may also work for Huntington’s and Parkinson’s, the researchers said.

It is “an elegant strategy” that provides “proof of principle” that this obstacle can be overcome, Steven Paul, a researcher at Weill Cornell Medical College in New York, said in a commentary published alongside the research.

The hallmark of Alzheimer’s is the formation of clumps of a protein called beta amyloid and tangles of another called tau. Scientists don’t know why they accumulate or become twisted, and there is debate as to whether they cause the illness or are an end-product of some different process.

Watts, the study leader, is developing a drug that blocks the action of an enzyme called BACE1 that’s involved in amyloid production. When his team tried to get their anti-BACE1 into the brains of mice and monkeys, they found that only a tiny fraction made it there.

“To do what we wanted to do in the brain, we had to dose like crazy, frequently and at high levels,” Watts said in an interview at Genentech’s campus. Such high dosages would be expensive and infeasible, Paul said.

“We needed a solution,” Watts said.

Watts turned to Mark Dennis, from Genentech’s department of antibody engineering, who took advantage of the fact that all cells, including brain cells, need iron. He engineered an antibody with two arms. One arm was the anti-BACE1 drug; the other docked with a receptor called transferrin that carries iron to brain cells, providing a ferry across the barrier.

The system allowed the researchers to deliver anti-BACE1 to the brains of mice, blunting the impact of the BACE1 enzyme and cutting in half the amount of amyloid in the brains of mice 48 hours after injection, according to the journal report.

More work is needed before the two-armed antibody can be tested in people, Watts said. A human version of the transferrin receptor antibody needs to be created and more safety testing must be done on large animals, he said.

“I think the prospects are quite strong” that the research could lead to a human therapy, said Vassar, who first identified and cloned the BACE1 enzyme in 1999.

Last August, Lilly released data showing that semagacestat, a drug directed against an enzyme involved in the production of amyloid, harmed patients instead of helping them. While that failure dampened enthusiasm for medicines that target amyloid, many researchers still see the plaques as being involved in development of the disease.

Pfizer, the world’s largest drugmaker, and Johnson & Johnson, of New Brunswick, N.J., for instance, are testing a drug aimed at amyloid called bapineuzumab, and Lilly is testing another, called solanezumab. Both are in late-stage trials that should be completed within two years, Weill Cornell’s Paul said in his commentary.


Post a comment to this story

We reserve the right to remove any post that we feel is obscene, profane, vulgar, racist, sexually explicit, abusive, or hateful.
You are legally responsible for what you post and your anonymity is not guaranteed.
Posts that insult, defame, threaten, harass or abuse other readers or people mentioned in IBJ editorial content are also subject to removal. Please respect the privacy of individuals and refrain from posting personal information.
No solicitations, spamming or advertisements are allowed. Readers may post links to other informational websites that are relevant to the topic at hand, but please do not link to objectionable material.
We may remove messages that are unrelated to the topic, encourage illegal activity, use all capital letters or are unreadable.

Messages that are flagged by readers as objectionable will be reviewed and may or may not be removed. Please do not flag a post simply because you disagree with it.

Sponsored by

facebook - twitter on Facebook & Twitter

Follow on TwitterFollow IBJ on Facebook:
Follow on TwitterFollow IBJ's Tweets on these topics:
Subscribe to IBJ
  1. Of what value is selling alcoholic beverages to State Fair patrons when there are many families with children attending. Is this the message we want to give children attending and participating in the Fair, another venue with alooholic consumption onsite. Is this to promote beer and wine production in the state which are great for the breweries and wineries, but where does this end up 10-15 years from now, lots more drinkers for the alcoholic contents. If these drinks are so important, why not remove the alcohol content and the flavor and drink itself similar to soft drinks would be the novelty, not the alcoholic content and its affects on the drinker. There is no social or material benefit from drinking alcoholic beverages, mostly people want to get slightly or highly drunk.

  2. I did;nt know anyone in Indiana could count- WHY did they NOT SAY just HOW this would be enforced? Because it WON;T! NOW- with that said- BIG BROTHER is ALIVE in this Article-why take any comment if it won't appease YOU PEOPLE- that's NOT American- with EVERYTHING you indicated is NOT said-I can see WHY it say's o Comments- YOU are COMMIES- BIG BROTHER and most likely- voted for Obama!

  3. In Europe there are schools for hairdressing but you don't get a license afterwards but you are required to assist in turkey and Italy its 7 years in japan it's 10 years England 2 so these people who assist know how to do hair their not just anybody and if your an owner and you hire someone with no experience then ur an idiot I've known stylist from different countries with no license but they are professional clean and safe they have no license but they have experience a license doesn't mean anything look at all the bad hairdressers in the world that have fried peoples hair okay but they have a license doesn't make them a professional at their job I think they should get rid of it because stateboard robs stylist and owners and they fine you for the dumbest f***ing things oh ur license isn't displayed 100$ oh ur wearing open toe shoes fine, oh there's ONE HAIR IN UR BRUSH that's a fine it's like really? So I think they need to go or ease up on their regulations because their too strict

  4. Exciting times in Carmel.

  5. Twenty years ago when we moved to Indy I was a stay at home mom and knew not very many people.WIBC was my family and friends for the most part. It was informative, civil, and humerous with Dave the KING. Terri, Jeff, Stever, Big Joe, Matt, Pat and Crumie. I loved them all, and they seemed to love each other. I didn't mind Greg Garrison, but I was not a Rush fan. NOW I can't stand Chicks and all their giggly opinions. Tony Katz is to abrasive that early in the morning(or really any time). I will tune in on Saturday morning for the usual fun and priceless information from Pat and Crumie, mornings it will be 90.1