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Researchers Hopeful About New Alzheimer’s Therapy

"Global Epidemic" Feared if Effective Treatment Isn't Developed Soon





June 12, 2007

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Researchers at NewYork-Presbyterian Hospital/Weill Cornell Medical Center believe they have made an important advance in the battle against Alzheimer's disease.

The researchers say they have identified naturally occurring antibodies in human blood that may help to defend against Alzheimer's as well as other neurodegenerative diseases.

The search for an effective Alzheimer's treatment becomes more urgent with each passing year.

More than 26 million people worldwide are estimated to be living with Alzheimer’s disease in 2006, according to a study led by researchers at the Johns Hopkins Bloomberg School of Public Health.

That number is expected to quadruple by 2050 as the baby boom generation ages. By 2050, 43 percent of those with Alzheimer’s disease will need high-level care, equivalent to that of a nursing home.

The newly found antibodies selectively target aggregates of beta amyloid proteins called "oligomers" that are toxic to brain cells, while ignoring the benign single-molecule forms of the same proteins.

The existence of such antibodies was predicted by animal studies, but they were never previously demonstrated to be present in substantial quantities in blood from normal humans.

Lead researcher Dr. Norman Relkin, a behavioral neurologist and neuroscientist at NewYork-Presbyterian Hospital/Weill Cornell Medical Center, said his team has been testing an antibody-based immunotherapy called Intravenous Immunoglobulin (IVIG) as a potential new treatment for Alzheimer's.

IVIG is made from the blood of healthy donors and was previously reported to contain small quantities of antibodies against beta amyloid.

“The effects of IVIG in lowering beta amyloid levels in Alzheimer’s patients in our Phase I clinical trial were much more profound than we expected,” Relkin said. “We couldn't readily explain this based on the low levels of anti-amyloid antibodies known to be present in IVIG. We suspected there might be another, unseen player.”

Relkin presented the findings this week at a conference in Washington, DC. He is director of the Memory Disorders Program at NewYork-Presbyterian/Weill Cornell and associate professor of clinical neurology at Weill Cornell Medical College.

NewYork-Presbyterian/Weill Cornell is currently leading a six-month Phase II study of IVIG in 24 patients with mild and moderate Alzheimer's disease, which is planned to be complete later this year. While this study may provide a signal of the effect of IVIG therapy to clinical outcomes, further investigation in larger controlled and longer-term trials will be needed to definitively demonstrate whether IVIG is useful in treating Alzheimer's.

Still, this discovery substantially boosts understanding of Alzheimer's and other neurodegenerative illnesses, the experts say.

Global Epidemic

The findings were presented at the Second Alzheimer’s Association International Conference on Prevention of Dementia held in Washington, D.C. and are published in the Association’s journal, Alzheimer’s & Dementia.

Researchers at the conference warned that global health care systems would be overrun with Alzheimer's sufferers if an effective treatment is not developed.

“We face a looming global epidemic of Alzheimer’s disease as the world’s population ages,” said the study’s lead author, Ron Brookmeyer, PhD, professor in Biostatistics and chair of the Master of Public Health Program at the Bloomberg School of Public Health.

“By 2050, 1 in 85 persons worldwide will have Alzheimer’s disease. However, if we can make even modest advances in preventing Alzheimer’s disease or delay its progression, we could have a huge global public health impact.”

According to Brookmeyer and his co-authors, interventions that could delay the onset of Alzheimer’s disease by as little as one year would reduce prevalence of the disease by 12 million fewer cases in 2050.

A similar delay in both the onset and progression of Alzheimer’s disease would result in a smaller overall reduction of 9.2 million cases by 2050, because slower disease progression would mean more people surviving with early-stage disease symptoms. However, nearly all of that decline would be attributable to decreases in those needing costly late-stage disease treatment in 2050.

The largest increase in the prevalence of Alzheimer’s will occur in Asia, where 48 percent of the world’s Alzheimer’s cases currently reside. The number of Alzheimer’s cases is expected to grow in Asia from 12.65 million in 2006 to 62.85 million in 2050; at that time, 59 percent of the world’s Alzheimer’s cases will live in Asia. To forecast the worldwide prevalence of Alzheimer’s disease, the researchers created a multi-state mathematical computer model using United Nations population projections and other data on the incidence and mortality of Alzheimer’s.

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