Pauline Anderson

March 20, 2009

March 20, 2009 (Czech Republic) – Researchers are getting tantalizingly close to developing biomarkers that can diagnose Parkinson's disease (PD), Alzheimer's disease (AD), and perhaps other dementia types.

Here at the 9th International Conference on Alzheimer's and Parkinson's Diseases, investigators presented an update on novel radioactive markers that can detect beta amyloid in areas of the brain that signal AD and dopamine deficits in other areas of the brain that indicate PD. All are in various stages of development.

As newer treatments come down the pipeline, some with possible adverse effects, it is becoming increasingly important to correctly identify these neurological disorders, said Michael J. Pontecorvo, PhD, vice president of clinical development at Avid Radiopharmaceuticals, in Philadelphia, PA.

Diagnosis Based on Pathology

"We're moving from a time where we make diagnoses based on symptoms to a time where we will diagnose based on the pathology of the disease, together with the clinical picture," Dr. Pontecorvo told Medscape Psychiatry. "These biomarkers tell us things about the pathology of these different diseases."

Dr. Pontecorvo discussed 2 of his company's promising biomarkers — 1 that binds to and shows the presence of amyloid in the frontal, temporal, precuneus parietal, and cingulate lobes and possibly elsewhere in the brain and the other that illustrates the absence of dopamine neurons in the stratum that might explain motor deficits in PD.

The idea is for these agents to be used together, said Dr. Pontecorvo. "When we talk about clinical syndromes, we talk now about a continuum of disease — there's AD, which is cognitive impairment without motor impairment. Then there's PD, which in pure cases involves motor impairment but no cognitive impairment. And somewhere in the middle, there's this Lewy body dementia, which is very hard to diagnose because it has features of both Alzheimer's and Parkinson's."

About 80% of patients with Lewy body dementia have too much amyloid and not enough dopamine. Using both biomarkers together will show the amyloid accumulation as well as degenerating dopamine neurons, he explained.

Clear Images in 90 Minutes

He added that his company's dopamine-deficit biomarker has advantages over competing markers in that clear images are available within 90 minutes of injecting it and using state-of-the-art scanning techniques. "And if you really push it, you can make the discrimination at 60 minutes."

Avid's amyloid agent is already in phase 3 clinical trials. "I can't put a precise time line on it, but within the next few years, the amyloid agent should be coming to market," said Dr. Pontecorvo. The company's Parkinson's agent is not far behind; it is in phase 2 trials.

Other promising biomarkers were also discussed at the meeting. For example, 1 agent — BAY-94-9172-PET (Bayer) — traces amyloid in the brain using positron emission tomography. Other agents can confirm the presence of tau protein — another signal for AD — in cerebrospinal fluid (CSF).

Undetected Alzheimer's

These and other biomarkers may eventually diagnose AD. As it stands now, there is no laboratory test that can confirm AD while a patient is still alive, so a diagnosis is made mostly by observing symptoms. About 10% of the elderly in the community have undetected dementia, and autopsies determine that 20% of patients diagnosed with AD do not actually have the disease.

That may not be significant today because patients with dementia typically receive similar treatment — often donepezil (Aricept, Eisai/Pfizer) — to help improve memory, attention, reason, and language. But as more targeted treatments become available, it will become increasingly important to determine the exact nature of the disease.

"Once we have targeted agents that are able to eliminate amyloid but that may have significant side effects, we are going to need to know that the patient really has amyloid," said Dr. Pontecorvo. Targeted drugs will likely be expensive, and therefore "you don't want to give them to the wrong patients," he said.

Neurons Already Dead

Further, these new biomarkers may be able to determine the nature of the disease at an early stage. Today, it takes about 2 to 3 years from onset of symptoms to a diagnosis of AD. In the case of PD, the "common wisdom" is that by the time patients develop symptoms, perhaps 50% of their neurons have already died, said Dr. Pontecorvo.

Mild cognitive impairment (MCI) is even more difficult to accurately diagnose, and research suggests family physicians fail to diagnose about 33% of mild dementias.

Other presenters at the meeting discussed biomarkers that could eventually distinguish patients with normal age-related memory loss from those whose cognition will deteriorate further.

So, will researchers be able to detect AD and PD at an early enough stage that treatment can halt deterioration? "That's certainly the hope; there are no data, but all of us at this meeting will be doing those kinds of studies in the next 5 to 10 years," said Dr. Pontecorvo

9th International Conference on Alzheimer's and Parkinson's Diseases. Presented Friday March 13, 2009.

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