BB&T National Editor and Staff Reports

In the face of continuing advances in medical knowledge, two particular disease sectors continue to haunt the planet: in undeveloped countries, the continuing prevalence of infectious diseases; in developed countries, the prevalence of Alzheimer's disease.

While infectious diseases can be beaten back by greater access to available therapies, Alzheimer's – likely to grow to epidemic proportions as a result of rapidly aging demographics – presents three key questions, with, as yet, no answers: How do you diagnose it? What causes it? And perhaps most difficult of all, what are the specific features that characterize it, tell us what it is, definitively?

Autopsy is the only provider of an exact diagnosis, and two of Alzheimer's characteristics are generally associated with causation: neurofibrillary tangles in the brain, supposedly resulting from protein abnormalities, and the presence in the brain of amyloid plaques, which contain a protein called amyloid beta.

The FDA's Peripheral and Central Nervous System Advisory Panel met in October to discuss the possibility of pushing to market a new group of radiopharmaceuticals potentially useful for identifying the sources of Alzheimer's, and serving as a possible early "prognostic," if not a definitive diagnostic.

Perhaps — most important of all – these new imaging agents could establish the validity of key biomarkers, with these biomarkers guiding development of an in vivo diagnostic and the development of drug therapies to treat Alzheimer's, both at the earliest stages.

The half-life of the first-developed agent for imaging plaques in the brain is short, just 20 minutes, and its use expensive, factors mitigating general clinical application. But new compounds under development feature half-life times up to two hours and easier use, offering opportunities for early scanning.

Three companies at the advisory panel meeting – with PET imaging agents in development and potentially useful for the identification of amyloid plaques – were Bayer (Leverkusen, Germany), GE Healthcare (Waukesha, Wisconsin), and Avid Radiopharmaceuticals (Philadelphia),

Bayer is developing an 18F-labeled PET tracer called BAY 94-9172; GE Healthcare is developing GE-067. Avid is developing 18F-AV-45, showing an affinity for specific binding to amyloid pathology, and the most advanced of the three in terms of clinical assessment.

The company in June reported its launch of a Phase II clinical study of the product, saying it is the first F-18 PET amyloid imaging compound to enter multi-center clinical research studies in the U.S. for the detection of amyloid plaque in patients with varying degrees of dementia. Avid is currently conducting clinical trials at more than 25 research centers across the U.S.

Alan Carpenter, PhD, JD, vice president, business development and legal affairs for Avid, told Biomedical Business & Technology that the company hopes to move into a Phase II trial early in 2009. While offering the usual hesitance concerning how rapidly the FDA might carry out its regulatory due diligence and act on approval, he suggested that the agency is likely to fast-track the product, with the earliest marketing okay coming in 2010.

Carpenter declined to put a dollar figure on potential future sales of the product. But he said it could be blockbuster status, if defined in terms of imaging. "From an imaging point of view, I guess you could consider it as having blockbuster potential, though markets for imaging products tend to be much smaller," Carpenter told BB&T.

He suggested that the major opportunity would be its use for finding an Alzheimer's drug, that product or products clearly having blockbuster potential. "Given the crisis we're faced with," he said, the applications for AF-45 "address a major healthcare problem. It would be fairly widely utilized, much like radiopharmaceutical imaging of the heart."

He said that the company is already partnering with some drug developers who are using AV-45 in their research on various compounds. Carpenter was careful to state that the company is not seeking FDA approval of the imaging agent as a diagnostic for Alzheimer's, but only of the identification of the amyloid plaques in the brain.

This makes it clear that medicine still has a ways to go to find a diagnostic or a therapy. A biomarker is not a disease, but Avid clearly hopes that its imaging agent can be used to determine if the presence of amyloid plaques is Alzheimer's defining biomarker.

New imaging technology avoids liver biopsies

As part of the larger push to reduce the number of invasive, painful and sometimes unnecessary diagnostic procedures, doctors at the Mayo Clinic (Rochester, Minnesota) are putting into practice their invention of magnetic resonance elastography (MRE) to identify liver fibrosis with high accuracy, helping to eliminate the need for biopsies.

The theory behind MRE seems very straightforward: Using a standard MR machine, the add-on technology produces color-coded images known as elastograms that indicate how internal organs, muscles and tissues would feel to the touch. Red is the stiffest; purple, the softest. A liver's elasticity or stiffness is invaluable in diagnosing liver disease. Liver fibrosis – the development of excessive scar tissue resulting in stiffness – is a common condition that can lead to incurable cirrhosis if not treated in time.

Doctors can't base their diagnosis on simply palpating the abdomen. A biopsy is needed to confirm. Even with biopsies, the results are not fully reliable.

With MRE, a special pad is placed on the patient's abdomen above the liver during a standard MRI procedure. A remote machine, connected by a tube to the pad, generates pulses or vibrations. Like ripples in water, the vibration causes waves to appear on MRI. Those waves are then interpreted by software into colors.

"The pulse sequence can show waves traveling through the liver," Jayant Talwalkar, MD, MPH, a Mayo Clinic hepatologist told BB&T. "One is blue and the other is red. That data is converted using a sophisticated math algorithm in a computerized fashion into a map of stiffness. Different colors represent different values of stiffness. Reds and yellows are really stiff. Blues are soft."

He explained that the elastogram provides a topographic map of liver. "In a normal liver, you would see a lot of purple and blue. Somebody with cirrhosis, you would see a lot of red and yellow," he said.

Talwalkar is co-investigator of a 113-patient study of MRE. Results were presented at The Liver Meeting, an annual gathering of the American Association for the Study of Liver Disease (Alexandria, Virginia), held in San Francisco.

Study participants all had liver biopsies in the year preceding the study and had a wide variety of liver diseases, including nonalcoholic and alcoholic fatty liver disease, hepatitis C, hepatitis B, autoimmune hepatitis, primary biliary cirrhosis and primary sclerosing cholangitis. Patients ranged in age from 19 to 78, and their body weight ranged from normal to severely obese.

"Results showed that elastography was highly accurate in detecting moderate-to-severe hepatic fibrosis even with the variety in age, types of liver disease and body size," Talwalkar said.

The underlying principle of MRE is that waves travel at a certain velocity; they move through stiffer tissue at faster speed and softer tissue at a slower speed.

Talwalkar said MRE could ultimately be used for other disease diagnoses. "I think there may be ways to develop this for cancer, muscle diseases, thyroid tests and Alzheimer's. There are a number of potential application in development now."

An implant aiding implanted device R&D

Texcel (East Longmeadow, Massachusetts) has created an integrated system for pushing forward the R&D done for medical device manufacturers making implantable stimulation devices.

Creating such a system was the thinking of Texcel, a company that has worked in the medical device industry for 21 years, according to Keith Checca, and in the "active implantable devices industry" for more than 10 years.

Checca, director of business development for Texcel, told BB&T that the company "had this idea for awhile. We were supplying kits and materials and customizing as we went for the last years or so. And our customers would ask, 'Do you have something off the shelf?' We said, 'No, but we can get there.'"

And as a result of its experience in creating these component parts, he said, Texcel developed the StimX to give "quick data, data incredibly valuable to the companies we work with."

Calling the Stim X the "the industry's first truly programmable, implantable customizable platform" for early testing of implantable electronic therapies, the company designed the device to have a wide range of test abilities – based on the parameters of currently available devices in this arena, Checca said – but making it programmable, thus customizable, for the particular effects being tested.

"Most of the devices that are used in implantable neurostimulation are within a certain range of output and a certain voltage and a certain length of time," he said. "We looked at the general applications out there and picked something in the middle, and then it has the programmable ability to be able to use upper and lower edges of what that hardware can handle."

The device itself includes an implantable stimulator, a laptop and output customization program, wireless communication, and charging modules.

Looking somewhat like a pacemaker, the stimulator is implanted in the animal's body, with leads then directed to a nerve or muscle or other tissue to be stimulated. Because the animal then wakes and continues regular active moments, the research can measure that effect "over a period of time," Checca noted.

He said the combined research/business goal for the device – to cost in the range of $50,000, with the company issuing a cost sheet today, he said – is to free researchers "from the hours and dollars that they'd otherwise invest in designing and developing their own devices – and to literally re-allocate their resources back into their research. It builds data, provides the additional information to continue the research. For venture-funded companies, it gives the data they need to determine if they should spend the money to move forward."

Among the possible applications for the device, Texcel says, are direct nerve and brain stimulation, strategies used for devices to treat such conditions as epilepsy, Parkinson's disease and clinical depressions .

The system enables the testing of a specific simulating effect, Checca noted, though there may be cases – "rare," he says – in which both an implantable device under development and the StimX would both be implanted.

Myriad spins off drug R&D from diagnostics

Myriad Genetics (Salt Lake City), a life sciences company that boasts of a strong cash position despite these tough economic times, said in late October that it will spin off its research and development business from its molecular diagnostics business to form two public companies, Myriad Pharmaceuticals and Myriad Genetics.

The spinoff is intended to help the companies "excel in their respective fields," acknowledging the different needs of a high-growth, profitable molecular diagnostics business and a pharmaceutical R&D business, the company said.

"By separating these businesses we believe each company will be better-positioned to deliver on their strategic visions and address their diverse operational and capital needs," Peter Meldrum, president/CEO of Myriad Genetics, said during a conference call. "Furthermore we believe this will be able to unlock the intrinsic value of both companies while giving each company the necessary resources to max their respective commercial opportunities."

Meldrum said the company plans to accomplish the separation of these businesses through a tax-free pro-rata dividend distribution to shareholders of Myriad Genetics during the first half of next year.

"We are excited about the future of both our molecular diagnostics business and our pharmaceutical business and we believe that this new strategic direction will allow each business to achieve its full potential," Meldrum said.

Gregory Critchfield, president Myriad Genetic Laboratories, told listeners that the company's strategy is "clear and working well." That strategy being to "focus on the molecular cause of disease and launch proprietary products that make a real difference in what patients and doctors do with the information," he said.

With the increased focus on the molecular diagnostics business, Critchfield said, the company has ramped up its business development activities.

"Myriad's cash position is very strong, allowing us to be in the enviable position to carefully evaluate and select product acquisitions that make sense and [we] believe that these activities will lead to the launch of future important molecular diagnostics products," he said.

iRIScope to help cut endoscope theft

Healthcare technology supplier Mobile Aspects (Pittsburgh), a that says it has come up with a unique solution to keep easily-stolen endoscopes in the hands of hospitals and out of the black market.

"With respect to theft, it seems to be a pretty big issue," said Bryan Christianson, VP of sales and marketing at Mobile Aspects. "There was a case of someone pocketing half a million [dollars] from selling endoscopes."

The company has designed iRIScope, a two-pronged attempt to secure the devices, through a software program that keeps a record of each devices use and a cabinet that locks and will not open until all the endoscopes are accounted for. iRIScope uses radio frequency identification (RFID) technology to keep an account of the endoscopes.

Specifically the cabinet-based solution secures endoscopes and manages access to the instruments while tracking utilization, repair and compliance with disinfection protocols. In addition to managing the equipment, the system advances patient safety in a variety of ways, most notably allowing for the automatic association of individual patients to unique endoscopes and procedures.

With the rapid growth of non-invasive procedures in areas such as gastroenterology, many healthcare facilities have invested heavily in the acquisition of endoscopic equipment, often an investment exceeding a million dollars.

"So it's simply a hardware-and-software solution," Christianson said. "Today most [healthcare facilities] don't do a very efficient job of recording the use of endoscopes."

Stringent protocols are mandated for the disinfection and reprocessing of such equipment. With breakdowns in these reprocessing protocols, significant risks for cross-contamination of equipment and patient infection can and often do emerge, he said.

What happens when a device isn't re-registered properly or not returned to the cabinet? "The cabinet locks up and an alert in the form of an e-mail or a message to a PDA appears and lets the physician or nurse know that there is a serious problem," Christianson said. "They're going to find out which of the devices was processed correctly and they're going to find out which one wasn't."