May 17, 2013

Promising New Paradigm for Testing Alzheimer's Drugs May Also Work for Other Age-Related Diseases

Yesterday we reported on the curcumin-based compound J147, which looks like the most promising drug candidate in the pipeline to treat Alzheimer's disease. It was developed by scientists at the Salk Institute for Biological Studies using a novel approach that may signal a new way of researching AD and other neurodegenerative disease-fighting drugs.

No question: a new approach IS needed. So far, Big Pharma has had little success with AD drugs, or with my own concern -- Parkinson's drugs.

Previous studies demonstrated that several compounds including J147 can prevent or delay onset of AD-like symptoms in young mice. But that methodology doesn't exactly address the issue for people, who typically experience symptoms before being diagnosed.

Salk Institute researchers therefore used older, AD-engineered mice, whose symptoms were already advanced. Treating these mice with J147 improved their memories in several tests. Examinations of their brains showed decreases in proteins associated with cell death, and increases in proteins that form the connections responsible for learning and memory. Yesterday's post provides more info about J147.

Salk Approach vs. Big Pharma's   
Salk lab chief David Schubert credits their novel drug discovery approach for J147's success treating Alzheimer's in mice. He explains:
Our approach to screening drugs is very different from that currently used by the pharmaceutical companies. AD is a complex disease associated with old age, and our goal is to make drugs like J147 that reduce the multiple toxicities associated with the disease, not just one. We believe J147 is the best AD drug candidate in the pipeline and will be effective if we can get it into the clinic.  
In contrast to the Salk Lab's multifaceted approach, Big Pharma's research on Alzheimer's (and other) drugs focuses instead on one molecular disease-related target. Success has been limited. For example, Big Pharma's focus on amyloid beta proteins as an Alzheimer's target has repeatedly failed to provide useful drugs. While amyloid beta plays some role in the disease, Schubert says, it's far from the whole story.

Big Pharma researchers typically experiment on young mice, genetically engineered to acquire Alzheimer's later in life -- not a great model for the way AD plays out in the real world. Unlike Big Pharma's lab mice, people develop symptoms and THEN get treatment. That's why Schubert's team waited for the lab mice to get old and to exhibit memory problems before putting J147 in their food.

The causes of AD are not well understood. Some studies suggest that less than 5 percent of all AD cases are caused by gene mutations that regulate the metabolism of the amyloid beta peptide. Nonetheless, most of the drugs for treating AD are designed to reduce amyloid beta accumulation.

The Salk Institute scientists are using living neurons grown in laboratory dishes to test whether new synthetic compounds like J147 -- based on natural products derived from plants -- might protect brain cells against various pathologies associated with brain aging.

In light of J147's apparent rodent successes, the Salk Institute team demonstrates the potential of a new drug discovery paradigm for AD and other neurodegenerative diseases. In this paradigm, a candidate drug doesn't simply target a single molecule; instead, it takes into account an array of age-related markers for neurodegeneration.

Meanwhile, Big Pharma's paradigm continues to rack up its lousy track record. Just last week, the research results were reported on Baxter International's Alzheimer's drug candidate Gammagard. It fared no better than a placebo.

Big Pharma hasn't had much success with its approach, but it has the money to keep repeating its flawed research model. And it continues to refuse funding trials on new and promising drug candidates based on natural substances.

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