The experimental treatment utilizes a viral-based gene transfer system, CERE-110, that makes Nerve Growth Factor (NGF). NGF is a naturally occurring protein that helps maintain nerve cell survival in the brain. In animal studies, NGF has been shown to support the survival and function of the neurons that deteriorate in Alzheimer’s patients. These neurons produce the chemical acetylcholine, which is important in memory and cognitive function. The hope is that improvement of this system’s function may lead to better memory performance in Alzheimer’s patients.

CERE-110 is an experimental treatment that will be injected into a specific region of the brain that is affected by AD, the nucleus basalis of Meynert (NBM).  CERE-110 has been studied in animals and humans.  In aged monkeys and rats, CERE-110 reversed brain degeneration.  Thus, these studies demonstrated that CERE-110 can safely induce long-term production of Nerve Growth Factor (NGF) by brain cells. A Phase 1 study conducted with humans was performed at Rush University in Chicago and the University of California San Diego, where the treatment was found to be generally safe and well tolerated. The 10 subjects underwent cognitive testing, measures of activities of daily living, and MRI and PET (positron emission tomography) scans. Researchers observed increases in brain metabolism in several cortical regions of the brain at six months and 12 months in some of the participants, as compared to other severity-matched individuals with AD.  This suggests a potential reversal of patterns typically observed in AD. With follow up ranging from six months to more than four years post-treatment, there have been no side effects thought to be caused by CERE-110.

The Phase 2 trial will be conducted at 12 U.S. sites, including Mount Sinai School of Medicine’s Alzheimer Disease Research Center.  The local study will involve approximately four to six volunteers between the ages of 50 and 80 with mild to moderate Alzheimer’s symptoms.

For more information about this study, please contact Judy Creighton, M.A., at 212-659-8886.

For Newsweek, Dr. Gandy stated, “I would say that conventional wisdom in the field . . . is that an amyloid benefit would mean amyloid-lowering. Certainly, up until now, no one has been looking to treat Alzheimer’s by raising amyloid levels. [So] it was startling to observe that a compound with an apparently beneficial clinical effect on cognition caused acute elevation of amyloid beta levels in 3 out of 3 systems, in 2 labs.” One of the most obvious implications of this finding is that pharmaceutical companies that are hoping to  discover amyloid-busting compounds may be taking the wrong approach. Although the data is still “not enough to make an educated guess,” the role of Dimebon in the world of Alzheimer’s research may continue to be an important research effort for the treatment of this disease.

The study found telephone and in-person assessment to be comparable, suggesting that telephone assessment may be a useful, cost-effective and time efficient alternative to in-person assessment of cognition in the elderly. Dr. Mitsis concluded, “Although telephone assessment is not a substitute for in-person assessment as conducted by neuropsychologists, many elderly patients don’t have the resources to access a neuropsychologist or ability to spend hours getting to the doctor’s office or clinic to receive an evaluation, especially one that would potentially be conducted every few months should that person decide to participate in a clinical trial.”

The study, published in the journal Molecular Neurodegeneration, tested the impact of several diets for their effects on Alzheimer’s disease pathology in mice. “Given the previously reported association of high-protein diet with aging-related neurotoxicity, one wonders whether particular diets, if ingested at particular ages, might increase susceptibility to incidence or progression of Alzheimer’s disease,” says lead study author Samuel E. Gandy, M.D., Ph.D., Mount Sinai Professor in Alzheimer’s Disease Research.

Dr. Gandy led an international team that included researchers from the United States and Canada.

The researchers tested four different diets on mice that had been genetically altered to be susceptible to Alzheimer’s disease. The mice were fed either the standard commercial diet that all mice in the facility receive; a custom-made high-fat, low-carbohydrate diet; a high protein, low carbohydrate diet; or a diet high in carbohydrates, but low in fat. The mice consumed these diets beginning at age four weeks until they were 18 weeks old. The researchers then looked at the brains and body weights of the mice, as well as plaque build-up and differences in the structure of the hippocampus, a brain region involved in memory.

They found that mice fed a high-protein, low-carbohydrate diet had brains 5 percent lighter than all the other mice, and regions of their hippocampus were less developed. Surprisingly, mice on a high-fat diet had raised levels of plaque proteins, but no loss of brain mass. This dovetails well with the knowledge that some fats, such as cholesterol, raise plaque levels, while other fats, such as those found in fish oil, protect from plaque.

One theory, says Dr. Gandy, is that a high-protein diet may leave neurons more vulnerable to Alzheimer’s disease plaque, but more research must be done to weed out the neurological impact of consuming different diets.

“At the end of the day, these are mouse experiments,” says Dr. Gandy. “Next, we want to see whether this is important for humans. There is enormous interest in identifying high-risk dietary components, but studying diets as though they were drugs is very challenging and, as with drugs, randomized double-blind clinical trials will be required if we are ever to be able to prescribe a diet that lowers the risk for Alzheimer’s.”

The association between diabetes and AD appears quite strong amongst patients who carry the ApoE 4 allele, an inherited risk factor for the development of AD.  The association between these two diseases is also strong in diabetic patients treated with insulin, a very common medication used to control blood sugar levels.  In addition, loss of brain tissue itself, something also seen in patients with AD, seems to be more severe in elderly patients treated with insulin.  There seems to be something about high levels of insulin that puts patients at risk for developing AD, as the “hyperinsulinemic state” typical of some forms of diabetes doubles the risk of AD.  This is a condition that many diabetic patients experience when their own bodies produce too much insulin because their cells have become less responsive to normal levels of insulin.  It has been shown that this “hyperinsulinemic state” may increase inflammation and affect the processing of molecules that lead to AD, potentially promoting memory impairment and AD.  Interestingly, In addition, therapies that target this state show promise in improving cognition in patients with AD.

Other relationships between diabetes and memory loss, focusing more on demographic factors, have also been found.  The Rancho Bernardo Study demonstrated a fourfold increase in cognitive decline in women with diabetes.  This effect was not seen in men.  In addition, improving control of blood sugar could actually ameliorate reduce this risk in women.  In the California SALSA (Sacramento Area Latino Study on Aging) study patients of both sexes with diabetes were less likely to

develop cognitive and physical decline symptoms if they were taking diabetes medications.  Despite the work that has been done so far, this area of research is still in its early stages.

The presence of memory loss and other cognitive impairments can interfere with almost every area of elderly patients’ medical care.  This is especially so for individuals with diabetes, as patients with this condition must monitor their blood sugar levels, understand complex medication regimens, and adapt to complicated dietary changes and lifestyle modifications.  In addition, patients’ rapidly changing treatment plans, many of them carrying the potential for dangerous adverse effects, further complicate the treatment management of patients with diabetes and concurrent cognitive deficits.  Although researchers have begun clarifying the links between diabetes and AD, much is still not understood about how they may affect one another.  Given the apparent associations between the two diseases, it is of particular interest to understand the molecular mechanisms underlying these interactions, as well as ways of preventing or ameliorating the effect of diabetes on memory.  With an increasing percentage of America’s elderly population being affected by both diabetes and AD, better understanding of the possible relationship between these illnesses may have significant implications for the prevention and treatment of AD.