Alzheimer’s-disease probe nears approval

Imaging technique could help to resolve questions about brain plaques associated with the condition.

Florbetapir reveals amyloid plaque build-up (red) in the brain of someone with Alzheimer’s disease (bottom), which is absent in a healthy brain (top).ELI Lilly/Avid Radiopharmaceuticals

An imaging agent that reveals a signature of Alzheimer’s disease in the brain — given conditional support last week by advisers to the US Food and Drug Administration (FDA) — is likely to be more valuable to scientists than to patients.

The agent, called florbetapir (Amyvid), enables physicians to determine whether Alzheimer’s disease is the cause of a patient’s dementia. In the future, it may also help them to catch the disease before obvious symptoms appear, a hope that has sparked fresh debate about the value of early diagnosis for a devastating, untreatable disease. The panel of advisers — whose guidance is usually, but not always, followed by the FDA — also stated that the test should not be given final approval until its developers demonstrate that clinicians can uniformly interpret its results.

“The importance of the decision is probably bigger for research in the near future than it is for clinical practice,” says William Thies, the chief medical and scientific officer of the Alzheimer’s Association based in Chicago, Illinois, a nonprofit organization that funds research on Alzheimer’s disease.

Physicians diagnose Alzheimer’s disease only after memory loss interferes with daily activities. By then, “there’s so much irreversible damage that it might be too late to hope for an effective treatment”, says Gil Rabinovici, a neurologist at the University of California, San Francisco. Definitive confirmation comes from autopsy, with the presence of characteristic lesions in the brain caused by clumps of the peptide amyloid-β. These amyloid plaques are hypothesized to be the cause of the memory loss.


Some researchers already use a reagent called Pittsburgh Compound B to image amyloid plaques in people suspected to have Alzheimer’s disease. The compound binds to the plaques, and its radioactivity can be detected using positron emission tomography. But the reagent is labelled with carbon-11: with a half-life of just 20 minutes, its use is limited to the handful of facilities that have an on-site cyclotron to prepare it.

In contrast, florbetapir is labelled with fluorine-18, which has a half-life of nearly two hours. That would be long enough to allow the compound’s manufacturer, Eli Lilly, based in Indianapolis, Indiana, to send labelled florbetapir directly to users without losing too much of the reagent to radioactive decay. The likely result: more and bigger studies of the relationship between amyloid and disease, says Thies.

A study published last week was crucial to the advisory panel’s decision. It confirmed that brain scans of living patients given florbetapir correlate with amyloid plaques found at autopsy after they died (C. M. Clark et al. J. Am. Med. Assoc. 305, 275–283; 2011 ). The Alzheimer’s Disease Neuroimaging Initiative, a project to improve clinical trials of candidate therapies for Alzheimer’s disease, has already incorporated florbetapir in its studies of hundreds of people suspected to have the condition. And Rabinovici hopes to test whether the reagent can distinguish between Alzheimer’s disease and frontotemporal dementia, which causes many of the same symptoms and is often misdiagnosed.

Florbetapir could help to resolve one of the fundamental disputes about Alzheimer’s disease: whether amyloid plaques kill brain tissue or are a side effect of the disease process. “Critics always tell me ‘well we don’t know yet if the amyloid hypothesis is true’,” says William Jagust, a neuroscientist at the University of California, Berkeley. “But this compound will finally allow us to examine just how important amyloid is.”

source: nature medicine

Dogs Can Detect Early Colorectal Cancer

Dogs Sniff Out Early Signs of Colorectal Cancer in Breath or Stool Samples

Jan. 31, 2011 — Specially trained dogs may be able to sniff out early signs of colorectal cancer in breath or stool samples, according to a new study.

Although canine cancer detection units aren’t likely any time soon, researchers say the findings suggest there are particular scents and volatile compounds associated with colorectal cancer that may help them come up with better ways to diagnose the often hard-to-detect and deadly disease.

“This study shows that a specific cancer scent does indeed exist and that cancer-specific chemical compounds may be circulating throughout the body,” researcher Hideto Sonoda, of Fukuoka Dental College Hospital in Fukuoka, Japan, and colleagues write in Gut. “These odor materials may become effective tools in CRC [colorectal cancer] screening.”

The study showed a Labrador retriever trained in scent detection was able to distinguish between cancerous and noncancerous stool and breath samples in 98% and 95% of cases, respectively.

The Study

In the study, the Labrador retriever completed 74 sniff tests, consisting of sniffing five breath or stool samples at a time in which one was cancerous, over a period of several months.

The samples came from 48 people with confirmed colorectal cancer and 258 volunteers with no cancer. Half of the comparison samples came from people with bowel polyps, which are benign growths that are thought to be a precursor of colorectal cancer.

The dog correctly identified the cancerous samples in 33 out of 36 of the breath tests and 37 of 38 stool tests.

Researchers say samples from smokers and other types of gut problems like inflammatory bowel disease or ulcers that might be expected to mask or interfere with scent detection did not pose a problem for the dog.

They say the findings are also consistent with previous research on successful canine scent detection for other types of cancers, including melanoma, bladder, lung, breast, and ovarian cancer.

If further studies confirm these results, researchers say less invasive colorectal cancer screening alternatives to colonoscopy may be developed using cancer-specific volatile organic compounds.

New Genetic Clues to Parkinson’s Disease

Researchers Identify Genetic Variants That May Be Linked to Parkinson’s


mature man

Feb. 1, 2011 — A new set of genetic variants has been implicated in the search for genetic risk factors that could lead to the development of Parkinson’s disease.

Researchers say six genetic factors that apparently affect the neurological disease have been previously identified. But in a new study, the researchers say they have now identified five more of the variants.

The research, a collaboration of investigators in the U.S., U.K., Germany, France, the Netherlands, and Iceland, is published online in the Feb. 2 issue of The Lancet.

Researchers say the study is the product of the largest genetic analysis of Parkinson’s disease ever done and that about 7.7 million possible variants were examined.

Genetic Roots of Parkinson’s

The researchers found that 20% of patients with the highest number of risk variants were 2.5 times more likely to develop Parkinson’s disease than the 20% of patients with the fewest genetic risk factors. The study results could point to new genes that need to be studied as scientists focus on genetic roots of Parkinson’s. The new findings have not been validated for clinical use.

The researchers say their study could be a starting point into further investigations of the causes of Parkinson’s.

“This study provides evidence that common genetic variation plays an important part in the cause of Parkinson’s disease,” the researchers write. “We have confirmed a strong genetic component to Parkinson’s disease which, until recently, was thought to be completely caused by environmental factors.”

The study concludes that the findings “provide an insight into the genetics of Parkinson’s disease” and its molecular cause and “could provide future targets for therapies.”

source: webMD

Colonoscopy Achieves Right-Sided Protection

New evidence bolsters the argument that colonoscopy can effectively prevent proximal colon cancers.

Prior data from Canada suggest that colonoscopy does not reduce right proximal colon cancer incidence and mortality (JW Gastroenterol Feb 20 2009). To investigate this issue further, researchers in Germany conducted a population-based, case-control study involving 1688 patients ≥30 with a first diagnosis of invasive primary colorectal cancer (CRC) and 1932 controls randomly selected from population registries. The aim was to assess whether undergoing colonoscopy during the preceding 10 years reduced the risk for CRC.

The overall exposure to colonoscopy was 41.1% for controls and 13.6% for case patients. Overall, receiving a colonoscopy during the previous 10 years was associated with a 77% lower risk for CRC. Colonoscopy was associated with an 84% lower risk for CRC in the left colon and a 56% lower risk in the right colon. Reduced CRC risk was observed for all stages of cancer and in patients who had undergone colonoscopy for screening or other indications.

Comment: Recent data from Canada suggest that right colon protection is achieved by colonoscopy when performed by gastroenterologists and by endoscopists with high polypectomy and cecal intubation rates (Gastroenterology 2011; 140:65). A previous case-control trial from the same German group that conducted the current study also reported a reduction in right-sided colon cancer after colonoscopy (Gut 2006; 55:1145). The differences in the magnitude of reduced risk findings between these studies might reflect that colonoscopy is performed primarily by gastroenterologists in Germany and primarily by primary care physicians and surgeons in Canada. Indeed, every study that has examined the issue has found better protection against cancer when colonoscopy is performed by gastroenterologists compared with other practitioners. Given that substantial variability also exists in performance by gastroenterologists, these results are a strong endorsement of the current move toward quality measurements in colonoscopy. The best validated quality measurements with regard to protection against cancer are the adenoma detection rate and the cecal intubation rate.

Douglas K. Rex, MD

Published in Journal Watch Gastroenterology February 4, 2011