BB&T Senior Staff Writer and Staff Reports

Sometimes the most debilitating medical conditions can be resolved by a very simple solution. Most often such solutions come from the academic setting, as is the case for a potential new drug-delivery device invented by researchers at the Massachusetts Institute of Technology (MIT; Cambridge).

It's just a small medical-grade silicone tube threaded over a shape-memory wire made of nitinol shaped like a pretzel but the MIT researchers think the new device may offer a better way to treat bladder disease.

The device, developed by Heejin Lee, PhD, and Michael Cima, the Sumitomo Electric Industries Professor of Engineering, is undergoing Phase 1 clinical trials, and is described in detail in a paper in the Journal of Controlled Release, available online and scheduled to appear in an upcoming print issue.

A new MIT spin-off company, Taris Biomedical (Lexington, Massachusetts) has already been established to carry out the testing and bring the device into production. Lee, who developed the device as part of his doctoral thesis work, is now working for the company as a product-development scientist.

The company's initial focus for the device is on bladder disease, particularly one called interstitial cystitis.

According to MIT, interstitial cystitis affects at least a half-million people in the U.S., mostly women, with perhaps an equal number undiagnosed. The only treatment that reduces the symptoms of painful and very frequent urination, which can be debilitating and make it impossible to work, is an infusion of the drug lidocaine into the bladder through a catheter, but the treatment only provides brief relief and needs to be repeated frequently, MIT notes.

Thus, Lee and Cima believe they have found a much better solution with the silicone tube. They fill the small tube with the solid drug, after drilling a tiny hole in the tube using a laser beam. The shape-memory wire is threaded through the tube, which is then straightened out, placed in a catheter, and inserted into the bladder. As soon as it is released there, the nitinol wire causes the device to spring back into a pretzel-like shape, which prevents it from being expelled from the bladder during urination, and thus it can slowly, steadily release the drug over a two-week period. According to the researchers, that would typically be long enough to treat an interstitial cystitis flare-up, something that may occur about three times a year.

Though it is initially being tested specifically for interstitial cystitis, Cima said that the same delivery system, if all goes well in the clinical trials, also could be used to deliver drugs for other bladder diseases, including chemotherapy for bladder cancer – the form of cancer that has the highest recurrence rate of all, in part because it is so difficult to deliver drugs to the bladder in a sustained way.

“The biggest problem with these treatments is the patients don't get the drug long enough,“ Cima said. He added that doctors try to make up for this shortcoming by using very high concentrations of drugs. The new device could potentially lead to smaller dosages, thus reducing side effects and adverse reactions, he said.

Cima predicts that if all goes well with the clinical trial the device could become an approved device by 2014. Compared to the discomfort of having a catheter left in place for an hour under the present standard treatment regime, in this device's initial Phase 1 trial after the quick insertion patients couldn't even tell that the device had been left in place, Cima said.

Elsewhere in the product pipeline:

• Advanced Cell Technology (ACT; Marlborough, Massachusetts) said the FDA has cleared its Investigational New Drug (IND) application to treat Dry Age-Related Macular Degeneration (AMD) using retinal pigment epithelial (RPE) cells derived from human embryonic stem cells (hESCs). ACT is now permitted to initiate a Phase I/II multicenter clinical trial to treat patients with Dry AMD, the most common form of macular degeneration in the world. There are no treatments available for this prevalent disease of an aging global population. Dry AMD, representing a substantial global market opportunity and afflicts between 10-15 million Americans. Age-Related Macular Degeneration has two predominant forms, wet and dry. Dry AMD is the most common form, accounting for almost 90% of all cases. The progress of Dry AMD includes a breakdown or thinning of the layer of RPE cells in the patient's macula, the region at the center of the retina responsible for high acuity vision. Over time, the progressive loss of RPE cells and accompanying loss of photoreceptors can cause severe vision loss and even blindness. ACT's Dry AMD therapeutic program uses RPE cells derived from hESCs to replace the lost RPE cells in the patient's eyes. ACT's RPE cell manufacturing process is protected by a number of broad patents, as is the use of hESC-derived RPE cells for treating macular degeneration. While the initial portion of the clinical trial will focus on safety, in subsequent clinical trials the company hopes to demonstrate that the RPE cells injected into the retinal space will be capable of slowing or halting progression of the disease, and potentially even restoring some visual acuity to patients.

• Alphatec Spine (Carlsbad, California) reported the first ever three-level Guided Lumbar Interbody Fusion (GLIF) procedure. GLIF is a lateral approach that provides the surgeon the ability to perform a 360-degree correction without repositioning the patient. The GLIF technique and ARC portal access system is designed to allow surgeons to perform lateral interbody fusion procedures with the opportunity for less intra-operative blood loss and minimized tissue disruption; while decreasing the recovery time for most patients. The three-level procedure using the ARC portal access system and instrumentation designed specifically for the GLIF technique. When augmented with posterior pedicle fixation, the ARC system eliminates the need to reposition the patient intra-operatively, thereby reducing the overall length of the lateral lumbar fusion procedure and potentially reducing operating room costs. Alphatec makes products for the surgical treatment of spine disorders, primarily focused on the aging spine.

• Arstasis (Redwood City, California) said the Arstasis One access device is available to physicians, nurses, patients, and cath lab technicians across the U.S. Until now, only a select number of physicians participating in Arstasis clinical trials and select pre-launch registries have been able to use the device. Since 1959, physicians have been using the Modified Seldinger Technique to insert flexible catheters into the femoral artery of patients for the purpose of performing procedures in the patient's arterial-vascular system. The most prevalent such procedure, diagnostic angiography, is thought to be performed more than half a million times per month worldwide. At the end of every such case, each patient is left with a substantial hole in his/her femoral artery (upper inner thigh) which typically takes significant effort and cath lab resources to close. With the Arstasis One Access Device, however, physicians create a shallow-angle needle pathway through the wall of the femoral artery. At the end of the procedure, when the sheath is withdrawn, the shallow-angle pathway collapses from the normal pressure of the patient's femoral artery blood flow from below and approximately 3-4 minutes of mild, non-occlusive finger-pressure from above, resulting in a quickly sealing access site.

• Covidien (Boulder, Colorado) reported the availability of the new Infinity MCable with Nellcor OxiMax technology as an integrated component of the Dräger Infinity Acute Care System in Europe. This system includes the portable Infinity M540 monitor. The Infinity MCable with Nellcor OxiMax technology adds two features to the compact Dräger monitor: Nellcor OxiMax specialty pulse oximetry sensors and Nellcor SatSeconds alarm management technology. The integration of pulse oximetry technology/clinician-controlled alarm management from Covidien with portable patient monitoring devices from Dräger, a manufacturer of medical equipment, underscores both companies' continuing commitment to improving healthcare delivery. This newly enhanced portable device now provides clinicians with state-of-the-art monitoring technology to optimize patient care as well as a technological solution to improve hospital efficiency and reduce the risk of human error. The Dräger Infinity Acute Care System is a networked system that integrates patient monitoring, therapy, and IT across the entire healthcare system to improve safety, efficiency, and quality of care. The system includes the Infinity M540, a portable patient monitor that moves with patients as they are transported throughout the hospital. During transport, the Infinity M540 monitor continuously captures, displays and stores vital patient data.

• Crospon (Galway, Ireland) has received FDA clearance to market a new imaging catheter for the measurement of sleeves created during bariatric surgery. The catheter is the latest development to the company's EndoFLIP range and is designed to assist surgeons during sleeve gastrectomy and gastric imbrication procedures. John O'Dea, CEO, Crospon said, “We continue to see positive results with the intra-operative use of EndoFLIP during gastric banding. By providing surgeons for the first time with an ability to measure the size of the sleeve they are creating, in real time during surgery, we believe it can increase the safety profile of the procedure by ensuring that the sleeve is not created too small, which in turn reduces the risk of leaks.“ Larry Fulton, VP sales for the Americas, Crospon emphasized the relevance of the new EndoFLIP imaging catheter for bariatric surgeons, “We are seeing a growing interest in the EndoFLIP system to assist surgeons performing the newly emerging gastric imbrication sleeve procedure. Whereas this newer emerging sleeve procedure is less invasive by virtue of no stomach being removed, the very fact that the stomach is kept intact presents an added challenge for the surgeon in measuring the size of the sleeve being created. We believe that the ability to measure the size of the sleeve will be an essential element in creating appropriately sized sleeves safely and consistently during gastric imbrication surgery.“

• Illumina (San Diego, California) introduced its next generation of iSelect custom genotyping products that allow researchers to design custom arrays containing from 3,000 up to 1,000,000 markers, with the flexibility to add supplemental content to their array designs. The company said the additional marker and add-on content capabilities enable researchers to draw on the latest advances from genome-wide association studies, next-generation whole-genome sequencing, and exome sequencing studies for variant confirmation, fine mapping, and target validation. iSelect also delivers the flexibility in plexity, pricing, and content that applied markets need to transition to the latest genomic tools. Illumina makes life science tools and integrated systems for large-scale analysis of genetic variation and function.

• Lineagen (Salt Lake City) reported the launch of its FirstStepDx integrated genetic testing and counseling service to assist pediatricians and family physicians with the earlier, more accurate diagnostic evaluation of autism spectrum disorders (ASD) and developmental delay (DD). FirstStepDx testing identifies certain genetic factors associated with ASD and DD. Early diagnostic evaluation of children with ASD is critical so that they can receive the earliest possible proactive intervention. FirstStepDx integrates genetic testing technology with pre- and post testing-consultation, provided by Lineagen's certified genetic counselors. The diagnosis of ASD and other conditions of childhood development can be slow, expensive, and frustrating for all involved. FirstStepDx says it addresses the backlogs and long waiting periods often associated with the evaluation of developmental disorders, by providing to the community physician the innovative molecular diagnostic tests and genetic counseling services that have been previously limited to specialist urban medical centers.

• Nanosphere (Northbrook, Illinois) reported FDA clearance for the Verigene Respiratory Virus Plus Nucleic Acid Test (RV+) on the Verigene System. The RV+ test expands Nanosphere's existing test capabilities for the detection of respiratory viruses. In a single test, the RV+ provides Influenza A, Influenza B, RSV A, and RSV B detection, and further subtypes Influenza A as H1, H3, or 2009 H1N1. The RV+ automates the steps of viral RNA extraction, multiplexed RT-PCR amplification, and target detection on the Verigene System and requires only a single pipetting step. Operationally similar, Nanosphere's existing respiratory assay cleared on the same Verigene System received a CLIA categorization of “moderate complexity.“ The RV+ test does not contain the recommendation to confirm all negative results with culture-based detection methods. Additionally, the random access, rapid turn-around time, and ease-of-use attributes allow any hospital to benefit from the high sensitivity and specificity of molecular testing without sacrificing the convenience and accessibility of rapid testing.

• Neogen (Lansing, Michigan) said its rapid test for Salmonella enteritidis (SE) has been determined to be equivalent to the FDA's traditional testing method in accuracy, precision, and sensitivity for detecting SE. The FDA's determination of equivalency will allow egg producers and processors to use Neogen's Reveal for SE to shorten the testing time and comply with the FDA's recently implemented SE-regulations without further scrutiny. In November, the AOAC International validated the accuracy of the Reveal for SE system when testing either environmental or egg samples. “The FDA's determination of equivalency further validates our test as an invaluable tool to egg producers, as they comply with the FDA's new regulations, and seek to further reduce the likelihood of SE-contaminated eggs reaching consumers,“ said Ed Bradley, Neogen's VP of food safety. “Until our introduction of an effective rapid test for SE, the industry had to wait up to 7 days for an outside laboratory's test results. Reveal for SE enables the industry to get quicker results – and provides the accurate answer they need to manage their flocks and egg production.“

• Pico-Tesla (Littleton, Colorado) has expanded its ongoing phase III pivotal clinical trial by adding three principal investigators, including two university-affiliated clinicians: one in Denver; and one in Tampa. In addition, Pico-Tesla said that enrollment is approaching 50% of the patients required for this pivotal clinical trial. The purpose of the ongoing phase III pivotal clinical trial is to demonstrate the efficacy of Pico-Tesla's Magneceutical Therapy as an adjunctive therapy to improving aspects of health and quality of life that are relevant to patients with Parkinson's disease. Pico-Tesla's Magneceutical Therapy involves the use of a low-level electromagnetic field applied by a specially designed device – the Resonator – along with proprietary therapeutic protocols and is currently in clinical trials to determine its effectiveness for improving the signs and symptoms of several diseases, including Parkinson's disease, atrial fibrillation, Alzheimer's disease, fibromyalgia and osteoarthritis.

• Puritan Medical Products (Guilford, Maine) reported the introduction of a new line of high-performance flocked products, the HydraFlock and UltraFlock swabs. The development of these products is a direct result of Puritan's ongoing effort to meet the evolving needs of the diagnostic market, which has led to a rapid expansion of the company over the last two years, the company said. “We've had to evolve and be diverse,“ said Timothy Templet, executive VP of sales. “Human diagnostic testing is a fast changing market, and we're making the commitment to stay at the forefront of this market.“ Puritan's process affords a combination of sophisticated fiber creation and innovative applications, yielding a specimen collection device with extremely high performance metrics. This is achieved without the addition of fiber treatments, resulting in a sample collection device that's totally free of interfering substances which can negatively affect the integrity of the swab.

• ReSound (Bloomington, Minnesota) has created a Remote Microphone Technology that enhances natural directivity, spatial awareness and wind noise performance in hearing aids. The Remote Microphone Technology uses a thin tube to connect the hearing aid to a microphone that is tucked into the concha cymba area of the external ear. The remote microphone uses the natural effects of the pinna, as they relate to directivity, high frequency amplification and wind noise reduction. The body of the hearing aid is placed in the ear canal to create device retention and cosmetic appeal. Behind-the-ear and some traditional custom hearing instruments have less-than-ideal microphone placement compared to the natural ear, causing distortions to occur if sound collection from the pinna is not used. Remote Microphone Technology takes advantage of the pinna effect to preserve natural localization (including front-back localization performance) and directional cues.

• Zimmer Holdings (Warsaw, Indiana) launched the Zimmer NexGen LPS-Flex Mobile Bearing Knee with Prolong Highly Crosslinked Polyethylene (XLPE) in the U.S. The LPS-Flex Mobile Bearing knee provides an anteriorly-positioned pivot near the entry point of the anterior cruciate ligament (ACL), replicating the anatomic center of knee rotation. During in vitro wear simulator testing, the LPS-Flex Mobile with Prolong Polyethylene system demonstrated an 83% wear reduction compared to conventional polyethylene.