DiaGenic and ExonHit Therapeutics recently said they have developed genetic biomarker panels capable of diagnosing Alzheimer's patients, and that that they may seek to commercialize the panels in the future using array platforms.
The two European diagnostics companies made their remarks at the 8th International Conference on Alzheimer and Parkinson diseases held in Salzburg, Austria, two weeks ago.
One of the greatest obstacles to an effective Alzheimer's diagnostic has been developing a test that doesn’t require the extraction of brain tissue. To bypass this problem, both DiaGenic and ExonHit developed tests that use blood samples to detect gene signatures associated with Alzheimer's.
At the Salzburg meeting, DiaGenic presented the results of two validation studies that used an internally developed gene signature together with Applied Biosystems’ TaqMan assays and GE Healthcare’s CodeLink bioarrays to correctly differentiate between Alzheimer's patients and Parkinson's patients.
According to Dag Christiansen, DiaGenic's marketing director, the firm is now planning for more extensive clinical studies that will form a basis for CE marking in the future.
So far, DiaGenic has been mum on whether it will choose to commercialize its test using an RT-PCR based platform, like TaqMan, or an array platform. Christiansen said that GE’s decision to discontinue its CodeLink line next month will not affect DiaGenic’s plans for the Alzheimer's test (see BAN 12/19/2006
). DiaGenic has used platforms sold by Applied Biosystems and Agilent Technologies to validate findings in the past.
"We are pleased with the results on CodeLink and are confident that we will be able to achieve the same accuracy on other custom array platforms of similar quality,” he wrote BioArray News in an e-mail last week. “We are looking into other custom array platforms."
ExonHit’s panel, which also uses blood, uses an internally developed signature based on 60 biomarkers that were able to successfully distinguish Alzheimer's patients from controls. The company said it plans to run follow-up clinical validation studies.
ExonHit has not discussed its plans for what platform its Alzheimer's panel could use, although the firm does have strong ties to both Agilent Technologies and Affymetrix, which manufacture its line of splice variant arrays.
John Jaskowiak, ExonHit’s vice president of business and marketing, told BioArray News in an e-mail last week that the firm’s R&D activities “are still in their early stages and the commercial plans are work in progress.
"We have had interest in the field of neurological diseases for some time now and are developing our own therapeutic pipeline and are at various stages of pre-clinical and clinical development in the Alzheimer's disease arena," Jaskowiak wrote.
"With that said, the company intends to work with carefully selected partners who will be responsible for conducting further product development and commercialization," he added.
Jaskowiak also mentioned that ExonHit has strong ties to the French diagnostics company BioMerieux, and that the duo recently expanded an agreement to develop blood-based diagnostics for a number of cancers (see BAN 1/16/2007
A Complex Disease
But Jaskowiak cautions that it will take longer for an array-based Alzheimer’s test to reach the market compared with a product like Roche’s AmpliChip, which tests for drug metabolism, or Agendia’s MammaPrint, which tests for breast cancer recurrence.
"Alzheimer’s disease is a complex and highly factorial disease,” Jaskowiak wrote. It represents one of the most overdiagnosed and misdiagnosed mental-function disorders of older Americans, according to the National Institutes of Health.
"To develop diagnostics one needs ready access to gold standard reference samples that cover the entire spectrum of the disease. Put simply, this is easier to obtain with cancer samples and harder to obtain with Alzheimer's patients."
"There are over 70 different disease entities that cause dementia, which complicate the diagnosis of patients, and currently only post-mortem examination of the brain can conclusively yield a proper diagnosis," Jaskowiak added.
Jaskowiak expressed hope that the continuing availability of higher-density microarrays could eventually yield an "accurate, sensitive, and specific assay for AD."
Another issue confronting companies developing array-based diagnostics for the disease is access to samples. "One of reasons why array-based Alzheimer’s diagnostics seem farther back in the pipeline is clearly the challenge with access to samples [because] brain biopsy is not readily performed," said DiaGenic’s Christiansen. "This is why our concept of using blood is so appealing."
"Firstly, the disease occurs in the brain where biopsy samples are almost impossible to obtain in the living patient,” he told BioArray News
in an e-mail last week. “Secondly, diagnosing Alzheimer's disease at the early stages with conventional techniques is extremely difficult no matter what method is employed.
"The problem lies with diagnosing the disease itself, rather than the diagnostic tools per se. To develop diagnostics one needs ready access to gold-standard reference samples that cover the entire spectrum of the disease. Put simply, this is easier to obtain with cancer samples and harder to obtain with Alzheimer's patients," McShea added.
Xiao Zeng, senior director of R&D and business development at SuperArray, which has sold an Alzheimer's chip as a research tool since summer 2005, explained in an e-mail to BioArray News this week that "most of the knowledge we have gathered so far about AD were from samples collected post mortem. .
“How would this translate into the profiles we can get from more accessible samples from live patients is still a question that needs to be answered."
According to Christiansen, another challenge for Alzheimer's diagnostics is the lack of disease-modifying drugs. He expressed hope that some of compounds currently in clinical validation would soon make it to the market, and wrote that this could reinforce the need for diagnostics for early-stage patients.
"Now there are more than 14 compounds in clinical phase III and the first might be on the market early next year,” Christiansen wrote. “The efficacy of the new drugs will depend on better and early diagnosis and this will have a great impact on the diagnostic market for Alzheimer’s disease.”