A Diagnostics & Imaging Week

You may not be able to teach an old dog new tricks, but doctors could one day have some new imaging tricks for diagnosing Alzheimer’s disease, a disorder that affects one in 10 people over 65 and nearly half of those over 85.

Siemens Medical Solutions (Malvern, Pennsylvania) recently reported plans to begin clinical trials under an investigational new drug application submitted to the FDA for an imaging biomarker that it hopes will identify Alzheimer’s disease before the onset of noticeable symptoms.

Siemens will collaborate with Alzheimer’s researchers at the University of California, Los Angeles to launch a Phase I, open label, single center safety study of what it says is one of the first imaging biomarkers designed to identify Alzheimer’s pathology specifically. The study will employ a new diagnostic technique developed by UCLA researchers that combines the new imaging biomarker and positron emission tomography (PET).

“The clinical diagnosis of Alzheimer’s disease is not definitive, but when it occurs, it is frequently late in the disease progression,” said Jorge Barrio, PhD, professor of medical and molecular pharmacology, UCLA, and co-inventor of the imaging biomarker. “This means that physicians would treat the disease only after it had already caused brain damage and impaired the patient’s memory and daily functioning. Use of this biomarker technology may provide physicians with an early diagnostic tool and information in order to help identify susceptible individuals and allow for the early start of a treatment plan before symptoms appear.”

Traditionally, PET, using the currently approved imaging agent 18F-fluorodeoxyglucose (FDG), measures metabolic function in cells. FDG-PET has been used for years in aiding diagnosis of various neurological conditions including Alzheimer’s and Parkinson’s disease, according to Siemens.

However, FDG cannot identify the abnormal brain protein deposits — amyloid plaques and tangles — that may cause Alzheimer’s, the company said. Current anti-dementia drug development is focusing on treating and preventing the accumulation of these deposits.

After Phase 1, the study protocol will focus on the use of the biomarker in patient populations and its potential to seek out tangles and plaques in the living brain of Alzheimer’s patients. Using PET imaging, biomarker molecules are considered to have the potential to “light up” the parts of the brain with high concentrations of the imaging biomarker; through analysis of the PET data, researchers can thus identify the disease specifically, and do so in advance of the onset of symptoms.

“With this imaging biomarker, we may not only have better early diagnosis of the disease but also the possibility of treating people to delay the onset of symptoms,” said Gary Small, MD, researcher, professor of psychiatry and biobehavioral sciences, UCLA, and co-inventor of the biomarker. “Our goal is to catch the disease in its earliest stages. If the technology proves successful in clinical trials, it could enable us to test new therapies and develop better drugs to manage the progression of the disease over time. It is clearly easier to protect a healthy brain than repair one that is already damaged.”

UCLA researchers discovered that the new imaging technique might just work with its biomarker, which the Siemens study will ultimately determine.

The UCLA study — on which the new Siemens imaging method is based — enrolled 83 volunteers with self-reported memory problems who had undergone neurologic and psychiatric evaluation and PET. On the basis of cognitive testing, 25 volunteers were classified as having Alzheimer’s disease, 28 as having mild cognitive impairment, and 30 as having no cognitive impairment (healthy controls).

PET was performed after injection of FDDNP, a molecule that binds to plaques and tangles in vitro. All subjects also underwent FDG-PET and 72 underwent MRI. According to the study results, global values for FDDNP-PET binding were lower in the control group than in the group with mild cognitive impairment, and the values for binding in the group with mild cognitive impairment were lower than in the group with Alzheimer’s disease.

FDDNP-PET binding differentiated among the diagnostic groups better than did metabolism on FDG-PET or volume on MRI, according to the study results. The researchers concluded that FDDNP-PET scanning can differentiate people with mild cognitive impairment from those with Alzheimer’s disease and those with no cognitive impairment.

The study by the UCLA researchers was published Dec. 21 in The New England Journal of Medicine.

According to the Alzheimer’s Association (Chicago) about 4.5 million Americans have Alzheimer’s disease, and by 2050 that number could range from 11.3 million to 16 million.

“Siemens’ clear objective is to move toward researching the causes of disease, rather than just managing the resulting conditions,” said Michael Reitermann, president, Molecular Imaging Division (Hoffman Estates, Illinois), Siemens Medical Solutions. “By aiding in the detection of diseases at much earlier stages, new imaging biomarkers may ultimately lead toward more personalized medicine.”

After the Phase I study, depending on its outcome, the company said it plans to initiate a larger multi-center clinical trial.

Siemens Medical Solutions has recently made key acquisitions in the area of in vitro diagnostics as it becomes what it says will be “the first full-service diagnostics company.”