New chemical classes of preclinical compounds identified for Alzheimer’s disease

Mar 4 2010

In an announcement today, Mount Sinai School of Medicine (MSSM) and Medisyn Technologies, Inc. said they have identified new chemical classes of preclinical compounds that may eventually lead to the first effective management of toxic amyloid aggregation and accumulation in the brain— an abnormal biological process long suspected by many researchers to be a major culprit in the onset and progression of Alzheimer’s disease.

“Historically, researchers have been discouraged by the high failure rate of many promising Alzheimer’s treatments”

Medisyn’s Forward Engineering™ technology and Dr. Giulio Maria Pasinetti at MSSM have identified eight novel drug leads from new chemical classes not previously associated with Alzheimer’s disease treatment. All eight leads have significant in vitro results when tested for β-amyloid lowering and anti-aggregation activity.

β-amyloid is an aberrant protein fragment cleaved from a normal human protein called the amyloid precursor protein (APP). In a healthy brain, these protein fragments are broken down and eliminated. In Alzheimer's disease patients, soluble β-amyloid peptides accumulate in high molecular weight oligomers, compromising healthy brain neurons and ultimately influencing their functions.

Two of these drug leads have been tested in vivo and effectively lower the amount of β-amyloid in the brain. They also lower the presence of aggregated β-amyloid (high molecular weight oligomers) that is generally implicated in cognitive deterioration. Current published research suggests that compounds able to reduce β-amyloid and its oligomerization into toxic species might postpone brain degeneration, if not prevent it.

“This work represents an entirely new approach to developing drugs for Alzheimer’s treatment,” explained Dr. Giulio Maria Pasinetti, Saunders Professor of Neurology, Director of the Mount Sinai School of Medicine Center of Excellence in Novel Approaches to Neurotherapeutics in Alzheimer’s Disease, and Director of the Center of Excellence in Complementary and Alternative Medicine in Alzheimer’s Disease Research. “With Medisyn’s help, we have made significant progress towards the goal of finding novel compounds to lower β-amyloid in the brain and reduce its aggregation into toxic high molecular weight species. Based on what we have observed in animal studies,” Dr. Pasinetti explained, “it appears that we may have achieved a combined functional effect that lowers the amyloid load in the brain and reduces the amount of high molecular weight aggregates. Although the project is early in the process of developing an eventual therapeutic, the findings so far are very exciting and we are eager to study further,” Dr. Giulio Maria Pasinetti said.

The studies were conducted at the MSSM Center of Excellence in Novel Approaches to Neurotherapeutics in Alzheimer’s Disease in New York, directed by Dr. Giulio Maria Pasinetti. The Center of Excellence is nationally renowned, offering comprehensive translational research dedicated to the study and treatment of both normal aging and Alzheimer’s disease.

Today’s announcement follows two-years of collaboration between MSSM and Medisyn to identify drug therapies in new chemical classes that could be candidates for the first disease modifying drugs for Alzheimer’s treatment. There are presently no FDA-approved treatments to prevent onset or progression of this devastating disease. Drugs approved for use currently treat only the symptoms of the disease, and only for a limited time.

“Historically, researchers have been discouraged by the high failure rate of many promising Alzheimer’s treatments,” said David Land, President of Medisyn Technologies. “We are applying our technology to help improve that success/failure ratio by taking much of the guesswork out of the drug discovery process. We have collaborated closely with Dr. Giulio Maria Pasinetti at Mount Sinai to identify the most promising functional signatures to carry forward into a pipeline of new drug candidates. Together, we have identified eight compounds in eight new chemical classes that appear to have the combined functional benefits we sought,” he said. “That’s very encouraging progress in such a challenging therapeutic field.”

Medisyn’s Forward Engineering^TM technology platform compresses drug discovery time from years to months, improves the accuracy of lead identification and vastly reduces the cost of developing a new drug, which today can run into hundreds of millions of dollars. Medisyn works with academic partners like MSSM to discover promising drug candidates for diseases with unmet therapeutic needs. Once those leads have been identified and validated in vivo, Medisyn secures outside funding or a partnership with a pharmaceutical company to develop and commercialize the drug.

The next phase of the MSSM/Medisyn collaboration involves pre-clinical evaluation of the eight compounds to measure efficacy and toxicity.

Alzheimer’s: A Steep Decline in Health & Steady Rise in Prevalence

According to various estimates, Alzheimer’s disease affects between 4-5.2 million Americans with another 5 million suffering from early-stage disease. Almost 10 percent of people over 65 in the U.S. have Alzheimer’s; that prevalence jumps to nearly 50 percent of individuals 85 and over.

Alzheimer’s disease is the most common form of dementia but is not considered a normal part of aging. According to the Alzheimer’s Foundation, we can expect the prevalence of Alzheimer’s to jump dramatically by 2050 to between 11.3-16 million cases. There are no FDA-approved treatments to stop or reverse progression of the disease. The cost of caring for the current Alzheimer’s population is estimated to be $100 billion per year.