Three Drugs to Be Tested to Stave Off Alzheimer’s

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The Dementia Caregiver's Little Book of Hope [Kindle Edition

New York Times

By GINA KOLATA

Scientists have selected three different types of Alzheimer’s drugs to be tested in the first large-scale international attempt to prevent the disease in people who are otherwise doomed to get it.

It is one of three studies with the same goal that will start early next year. This one involves 160 people from the United States, Britain and Australia with a variety of gene mutations that cause Alzheimer’s with absolute certainty. Most of the test subjects will have no symptoms yet of the degenerative disease that ravages the brain, destroying memory and thought. But they would be expected to start showing signs of problems with memory and thinking within five years unless the drugs work. The hope is that by intervening early, the disease might be headed off.

Another study starting next year involves an extended family in Colombia that shares the same mutation. Anyone who inherits that mutated gene get Alzheimer’s disease. A third study will involve people in the United States age 70 and older who seem perfectly healthy and who do not have any known Alzheimer’s mutations but in whom, brain scans show, the disease is starting to manifest itself.

In recent years, as studies involving people who already have Alzheimer’s have failed, researchers increasingly have called for studies in those who do not yet have the disease, arguing that the time to intervene is before the brain is irreversibly damaged. So the new study with people who are destined to get Alzheimer’s unless a drug can stop it is a way to test that idea.

 “It’s an exciting opportunity,” said Dr. Ronald Petersen, director of the Alzheimer’s Disease Research Center at the Mayo Clinic, who is not involved with the study.

Maria C. Carrillo, vice president of medical and scientific relations at the Alzheimer’s Association, said the results would come quickly. Within a few years, as researchers simultaneously compare the three approaches to stopping the disease, they should know which drug, if any, is going to work. The association contributed $4.2 million to the study, more than twice as much as it has ever spent on a grant, Dr. Carrillo said.

The announcement comes at a time of transition for Alzheimer’s research. In recent years, investigators have discovered methods of spotting and tracking the progression of the disease before any clinical symptoms appear, using brain scans and spinal taps and sensitive tests of memory. They have led to what many think is the start of a new era in which drugs can be assessed without waiting for effects on profound symptoms.

That is a goal of the study whose drugs were announced on Wednesday. Known as DIAN TU, for Dominantly Inherited Alzheimer’s Network Trials Unit, it was designed to get the most information possible in as short a time as possible. Three-quarters of the subjects will get one of three drugs aimed at beta amyloid, a protein that forms the hard, barnaclelike plaques on the brain that are the hallmark of Alzheimer’s.

The drugs were chosen from among 15 that drug companies offered, said the study’s principal investigator, Dr. Randall Bateman of the Washington University School of Medicine in St. Louis. A committee assessed them, looking for drugs with the best evidence of effectiveness and the least likelihood of dangerous side effects. One concern is something called ARIA, for amyloid related imaging abnormality. People with the abnormality may have no signs that anything is wrong, but brain scans show what looks like a change in neural connections. ARIA is a rare side effect of some experimental Alzheimer’s drugs, and it is not clear what it means, but it is a concern and will be monitored closely, Dr. Bateman said.

For the first two years of the study, researchers will follow the subjects with scans and memory tests, looking for signs that the drugs are working. If one or more seems clearly effective, they will switch all the subjects to it and continue the study, looking for clinical benefits.

The drugs to be tested are gantenerumab, made by Roche, which binds to clumps of amyloid and allows it to be removed from the brain, and two drugs by Lilly. One, known as LY2886721, blocks an enzyme, beta-secretase, used to make amyloid. The other, solanezumab, attaches itself to amyloid that is floating free in the brain before it clumps into plaques, facilitating its removal.

Solanezumab was recently tested in people with mild to moderate Alzheimer’s and appeared to have no effect on the disease. But Lilly also handed over all of its data to a group of academic researchers, giving them complete control of the presentation of their analysis and publication, and the group noticed something interesting. The investigators pooled data from the company’s two large clinical trials of the drugs. In their extensive analysis, presented Monday at the American Neurological Association meeting in Boston, they reported that it improved Alzheimer’s dementia, particularly in mild cases.

“This is the best news we’ve had in a decade,” said Dr. Paul Aisen, an Alzheimer’s researcher at the University of California, San Diego. Dr. Aisen helped analyze the Lilly data and is also a member of the DIAN TU committee that helped select the drugs for the clinical trial.

DIAN is hoping that the same sort of exquisitely sensitive cognitive tests will provide the first sign that one of the drugs is working.

If any of the drugs come to market, they will be expensive, which raises issues of how patients will ever be able to pay for them.

Researchers said they would face that issue when they come to it.

“Right now we have to get treatments that work,” said Dr. Rachelle S. Doody, director of the Alzheimer’s Disease and Memory Disorders Center at the Baylor College of Medicine. “Then we can put pressure on to bring down the cost.”

Antibody Reaches Major Milestone in Collaboration with Roche

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Here is a great dementia resource for caregivers and healthcare professinals,


Your residents will love the Amazon Kindle Fire




Here is information on being the best caregiver you can be


Here is a way for nurses administrators, social workers and other health care  professionals to get an easyceu or two


Follow alzheimersideas on twitter

The Dementia Caregiver's Little Book of Hope [Kindle Edition

Reuters

Gantenerumab Clinical Trial Expanded to Pivotal Phase 2/3 Study

MorphoSys AG (FSE: MOR; Prime Standard Segment, TecDAX) announced today that its partner Roche (SIX: RO, ROG; OTCQX: RHHBY) has expanded the ongoing SCarlet RoAD Phase 2 clinical trial of gantenerumab for prodromal (early) Alzheimer's disease to a potentially pivotal study. The trial size will be increased from 360 to 770 participants, and a favorable outcome to the trial could be used by Roche to support a marketing application for gantenerumab. The expansion of the study triggered a clinical milestone payment to MorphoSys, the details of which were not disclosed. MorphoSys stands to receive further developmental milestones as well as royalties on product sales.

"This is a major step forward for a HuCAL antibody program that has genuine blockbuster potential", commented Dr. Marlies Sproll, Chief Scientific Officer of MorphoSys AG. "Gantenerumab is the first investigational antibody development program for Alzheimer's disease to be clinically tested in a setting for which there is great hope, namely the treatment of early-stage, pre-dementia subjects. A potential path to market for this program has become much clearer with this transition to a pivotal trial".

"We believe the greater opportunity to make a difference in patients' lives is in early diagnosis and intervention," said Luca Santarelli, Head of Neuroscience at Roche. "Our attempt is to utilize a biomarker-driven approach, leveraging both our pharmaceutical and diagnostics divisions to develop a companion diagnostic for gantenerumab to select patients at the prodromal stage, before significant damage to the brain has occurred."

Gantenerumab is an optimized, fully human antibody that was developed on behalf of Roche by MorphoSys scientists using the Company's proprietary HuCAL technology. Gantenerumab is unique amongst antibodies in development in that it binds to both the N-terminus and mid-section of the 42 amino acid amyloid-β peptide. It has been shown to break down amyloid plaque both in vitro and in vivo. In Phase 1 clinical trials conducted by Roche¹⁾, the antibody was found to bring about rapid, dose-dependent clearance of plaque from the brains of mild to moderate Alzheimer's disease patients. The ongoing clinical trial is designed to evaluate its effect on cognition and functioning as well as its safety and pharmacokinetics in patients with prodromal, or early-stage, Alzheimer's disease. In this phase of the disease, which can be characterized by measuring certain biomarkers, patients have only mild cognitive impairment and have not yet been diagnosed with Alzheimer's disease. According to recent research, amyloid plaque may accumulate even at this early stage in the brains of sufferers, and may lead to full-blown disease.

MorphoSys's clinical pipeline now comprises one program in phase 3 development, seven in phase 2 and twelve in phase 1. Of these, four are proprietary, as yet un-partnered programs, namely MOR103, which is in a phase 1b/2a trial for rheumatoid arthritis and a phase 1b trial in multiple sclerosis, MOR208, which is in a phase 1 trial for chronic lymphocytic leukemia and MOR202, which is in a phase 1/2a trial for multiple myeloma.

¹⁾ Reference: Ostrowitzki, S. et al (2011) Mechanism of Amyloid Removal in Patients With Alzheimer Disease Treated With Gantenerumab. Archives of Neurology, 68(10); 

Gantenerumab: New Alzheimer's drug shows early promise

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USA Today

The new study, which appears online Oct. 10 in the Archives of Neurology, is among the first to show the effects of an anti-amyloid drug in humans with Alzheimer's disease, but experts caution that while promising, more research is needed before this drug can be deemed safe or effective.
And, in what may turn out to be an equally important caveat, experts also say that it's by no means certain that reducing levels of amyloid plaque would stave off memory loss and the other mental declines associated with the disease because the role of the plaque in Alzheimer's isn't fully understood.
Alzheimer's disease is the most common form of dementia. Symptoms including serious memory loss, confusion and mood changes develop gradually and worsen with time. Recently, many strides have been made in diagnosing Alzheimer's disease earlier, but doctors have been stymied by a lack of effective treatments to stop or slow the course of the disease.
It's long been known that a protein fragment called beta-amyloid builds up in the spaces between nerve cells in the brains of people with Alzheimer's disease. The new drug, gantenerumab, targets these amyloid proteins by priming the body's immune system to recognize them as invaders.
Of 16 people with mild-to-moderate Alzheimer's disease, those who received two to seven infusions of the experimental drug every four weeks showed marked reductions in the amount of plaque in their brains via imaging tests that were conducted several months after their treatments.
By contrast, amyloid load increased among people who were randomized to receive the placebo. The new drug was given at either 60 or 200 milligrams (mg) doses. The higher dose yielded greater reductions in amyloid levels, the study showed. People who were given the 60 mg doses saw a nearly 16 percent reduction in the amount of amyloid, and those given the 200 mg doses saw a 36 percent reduction. The new study was conducted and funded by the drug's manufacturer, F. Hoffmann-LaRoche Ltd., in Basel, Switzerland.
The big question is whether or not reducing amyloid levels has any effect on the symptoms or progression of Alzheimer's disease, said Dr. Patrick Lyden, chief of neurology at Cedars-Sinai Medical Center in Los Angeles. "There is a growing concern that amyloid is a guilty bystander, but not the actual culprit in the brains of people with Alzheimer's disease, and taking away the bystander may not help the patient," he said.
There are approximately one dozen therapies, including vaccines, for Alzheimer's disease that are currently in the pipeline, Lyden noted. "They are all extremely exciting and promising in animals," he said. "This is the first one to show a preliminary result in people, but we have a huge way to go to make sure it is safe and improves symptoms."
Many in the Alzheimer's research community are awaiting these drugs with bated breath, but "none are ready for prime time," he said.
The leading theory of Alzheimer's disease is that an imbalance in the production or clearance of the amyloid plaque in the brain initiates a cascade of events that lead to dementia, explained Dr. Neelum Aggarwal, an associate professor of neurological sciences at Rush Alzheimer's Disease Research Center at Rush University Medical Center in Chicago.
"Accumulation of the plaques cause a variety of cellular responses: inflammation, neuronal death, and thus any potential treatment that can alter these processes would be beneficial," she said. The hope is that gantenerumab or other drugs like it will not only prevent amyloid from accumulating in the brain, but also slow down the cognitive impairment that occurs in people with Alzheimer's disease, she added.
That said, these experimental drugs carry the potential for serious side effects, including causing the immune system to go haywire. "The main issue that remains for this type of drug development is managing the immune response," Aggarwal said. Other side effects include a potentially fatal fluid build-up in certain areas of the brain. "This is problematic in that use of these treatments may carry a very high risk for neurologic complications, thus necessitating heightened monitoring, and diminishing its applicability as a treatment for a larger patient population such as the Alzheimer's disease population," she said.
If any of these drugs make it through the pipeline, it also needs to be determined who will get them, including whether the drugs will be given to prevent Alzheimer's in patients at high-risk of the disease or to treat it once it's started.
The need for a drug to delay the onset or slow progression of Alzheimer's disease can't be underestimated, Aggrawal said. In the United States alone, there are 5.4 million people with Alzheimer's disease, and the numbers are expected to increase to 13 million by 2050, when approximately three of every five people over the age of 85 will have Alzheimer's disease, she said.