Hope growing through new Alzheimer's research

Scientists have spent billions of dollars and countless hours in the past three decades to find effective treatments for Alzheimer’s disease, with somewhat disheartening results — only 1 percent of therapies tested have been approved, and none to date can slow the progress of the dementia-inducing disease.  

Recent findings, however, suggest the first treatments that slow the early stages could hit the market by 2020. Scientists at biotech Genentech Inc. in San Francisco believe an Eli Lilly and Co. drug called Solanezumab can “eat” the plaque that interferes with healthy connections or synapses between neurons that are brain key to memory. And because such plaque can form in patients some 10 years before symptoms are observed, the scenario suggests a window of time for intervention. Stage 3 clinical trials costing Eli Lilly some $1 billion are ongoing through October, with final data available sometime next year.

“How can we have gone 25 years without bringing a medication that’s successful to the marketplace? That answer is that we’re learning every step of the way,” explains Eli Lilly’s Senior Medical Director Eric Siemers. “It really is a very promising time for the field, and that’s one thing patients need to keep in mind — if they enroll in half the time, we’ll get answers much, much sooner.”

Genentech recently completed phase two clinical studies (cost: $350 million) of the drug modeled on antibodies already found in blood. The protein successfully reduced levels of the protein amyloid beta in the brains of early-stage Alzheimer’s patients with mild forms of the disease; the amyloid is thought by some to cause Alzheimer’s by forming plaque and tangles in the brain that clog synapses. Testing of patients afterward found a 35 percent reduction on average in the decline of cognitive reasoning, but some subjects in similar studies experienced swelling of the brain, and more research is needed.

“There was an overwhelming sense of relief that we saw some signals suggesting we’re having success,” said Genentech CMO Carole Ho. “That’s incredibly promising for early stages of the disease.”

In 2020 Genentech expects to wrap up a $100 million landmark study of 300 patients among a large extended family in Colombia genetically predisposed to Alzheimer’s because of a gene mutation. None have shown outward symptoms of the disease, and the hope is an anti-amyloid drug will halt the formation of plaques and tangles — and thus the disease itself.

Alzheimer’s already affects 5.4 million Americans and 40 million people worldwide; today, one in nine people ages 65 and older is inflicted. It’s the sixth leading cause of death in the U.S. (more than breast and prostate cancer combined), and is expected to cost the nation $236 billion this year. It will become more prevalent as baby boomers age. Scientists believe it occurs when a developmental process gone awry causes immune cells to “eat” healthy connections or synapses in the brain, instead of eating only weak or obsolete synapses as part of a normal pruning process that strengthens healthy synapses.

Virtually every pharmaceutical company worldwide is competing to come up with better therapies or a possible cure, with at least 20 clinical trials underway as of April. Fighting plaques is the foundation of most, though many believe a protein in the brain called tau is responsible for forming plaques and tangles.

In a recent study led by Beth Stevens of Boston Children’s Hospital, Stevens’ team found the combination of an amyloid with the protein C1q destroyed brain synapses in mice; the team will next track whether an antibody that blocks C1q can slow cognitive decline in human beings. Neuroscientist Edward Ruthazer called results to date “difficult to argue with,” adding he’s interested in a possible link between high levels of C1q in cerebrospinal fluid with full-blown Alzheimer’s later in life.

Biotech firm Biogen, which is based in Cambridge, Massachusetts, conducted similar clinical trials using its anti-amyloid Aducanumab and had similar success in removing existing plaque from the brains of early-stage Alzheimer’s patients. Results showed an average 80 percent improvement in the decline of cognitive reasoning, but side effects included swelling of the brain and headaches.

Among those predicting an effective drug on the market by 2020 are Dr. Dennis Gillings, chairman emeritus of the London-based World Dementia Council and founder of global biotech firm Quintiles. He says recent scientific progress addressing plaques in the brain has surpassed his expectations. "The original goal [of the council] was disease modification by 2025," he said. "I feel a lot more optimistic now: I wouldn't be surprised if we get there by 2020 or 2021."



BlogLindsey Kuhl