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Monday, May 6, 201 3

Vol. 17, No. 87

Insulet to develop U-500 insulin pump with Lilly By AMANDA PEDERSEN Medical Device Daily Senior Staff Writer

A fair amount of attention has been paid to obesity rates and subsequent Type 2 diabetes, both of which have spiked in recent years, but a lesser known problem is that a sizable portion of this population is insulin resistant and requires much higher doses of insulin to control their blood glucose. Eli Lilly (Indianapolis) makes Humulin R U-500 insulin, a form of insulin that is five times more concentrated than the more common U-100 insulin, and has seen an increase in demand for the more powerful type of insulin. The problem is that U-500 has not been approved for use in a pump, but healthcare providers prescribe it to insulin-resistant patients anyway, either in a syringe or a pump. “The number one question I get when I give a diabetes talk,” said Bruce Bode, MD, an expert on insulin delivery, “is See Insulet, Page 7

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Medtech Investing Europe MTI Conference

Ophthalmics come into sharper focus at BioAlps conference By JONATHAN GOLDSTEIN Medical Device Daily Israel Editor

In the last issue of Medical Device Daily (MDD, May 3, 2013), we described the Swiss MTI conference in Lausanne. Below we mention three additional exciting ophthalmic companies – all in the treatment of major eye diseases. Given their major activities in Europe, they chose to present at this European focused med-tech conference. In addition to Implandata (Hannover, Germany, described in the previous story) for improved continuous glaucoma measurement, another implant system for glaucoma – this time for treatment – is offered by startup Rheon Medical (Préverenges, Switzerland). Reduction of eye pressure is well accepted as a contributor to slowing down the damage to the optic nerve. Towards that See MTI, Page 8

Capital royalty’s $805M fund: ExThera Medical forges ahead sifting through surplus of deals with Seraph to treat sepsis By RANDY OSBORNE Medical Device Daily Contributing Writer

By OMAR FORD Medical Device Daily Staff Writer

Risk-shy investors who’d rather bank on approved products make up Capital Royalty L.P.’s second fund, $805 million worth of private equity for betting in increments of between $20 million and $200 million, though the amounts could go higher. “There are very good early stage venture capitalists,” such as Avalon Ventures, said Luke Düster, principal with Capital. “But, as the pathway to approval under the FDA becomes longer and more expensive, it requires either a significant amount of long-term-view strategic focus to get through that pathway, or a significant amount of capital or both.” Not everyone’s cup of tea, for sure, though Avalon has See Capital, Page 9

In the U.S., sepsis is the leading cause of death in noncoronary ICU patients, and the 10th most common cause of death overall, according to data from the Centers for Disease Control and Prevention (Atlanta). Sepsis is also more dangerous in elderly, immuno-compromised and critically ill patients. It occurs in 1%-2% of all hospitalizations and accounts for as much as 25% of intensive care unit (ICU) bed utilization. In ICU units worldwide it is a major cause of death, with mortality rates that ranging from 20% for sepsis to 40% for severe sepsis to more than 60% for septic shock. The annual cost of sepsis care is $17 billion. One med-tech firm has developed a device that it says has the potential to help treat the disease and perhaps cut See ExThera, Page 10

Don’t miss today’s MDD Extra: Neurology

Inside:

S&N reveals $300 million share repurchase plan...................................... 2 Eventus gets CE mark for Octava Pink cancer test................................... 3

To subscribe, please call Medical Device Daily™ Customer Service at (800) 477-6307; outside the U.S. and Canada, call (404) 262-5476. Copyright © 2013 AHC Media. Reproduction is strictly prohibited. Visit our web site at www.medicaldevicedaily.com.


Medical Device Daily™

Monday, May 6, 2013

Financings roundup

S&N reveals $300 million share repurchase plan A Medical Device Daily Staff Report

Smith & Nephew (London) reported that it is poised to hand back cash to shareholders through a $300 million share repurchase program. The company unveiled the buyback late last week as part of a new capital allocation that will also see a commitment to continuing investment and acquisitions. CEO Olivier Bohuon said there was scope to return surplus capital despite ongoing investment. “We will continue to invest in our growth products, franchises and geographies and maintain adequate headroom for further significant acquisitions,” he said. The company also said it was making a small acquisition in India by buying Adler Mediequip and with it the brands and assets of Sushrut Surgicals, a maker of orthopedic trauma products for the Indian market, for an undisclosed sum. In other financings activity: • SQI Diagnostics (Toronto), a life sciences company that develops and commercializes proprietary technologies and products for advanced microarray diagnostics, reported it raised gross proceeds of $3.845 million through a nonbrokered private placement of 5,126,044 units priced at 75 cents per unit. Each Unit consists of one common share and one common share purchase warrant. Each common share purchase warrant will entitle the holder to purchase one common share at a price of $1.10 for a period of two years from the date of issuance. After giving effect to the issuance of the shares and exercise of warrants of the Private Placement the Company will have 50,078,352 shares outstanding. In connection with the Private Placement, the

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company paid Kingsdale Capital Markets a cash finder’s fee of $269,000 of the gross proceeds and issued 512,604 compensation warrants entitling Kingsdale to acquire 512,604 Units at a price of $0.75 per Unit and expiring 24 months after the closing of the Private Placement. The Private Placement is subject to all necessary regulatory and stock exchange approvals. The securities being issued pursuant to the Private Placement will be subject to a four month hold period in accordance with applicable Canadian securities law. “SQI’s enhanced cash position enables us to deliver to our growing pipeline of pharma customers in the Diagnostic Tools and Services business segment,” said Andrew Morris, Chief Financial Officer of SQI Diagnostics. “This financing will also enable the Company to continue to build out our menu of IVD autoimmune tests focused on customers in the reference lab market.” • Vivo Therapeutics Holdings (Toronto), a developer of technologies for the treatment of spinal cord injuries (SCI) and other neurotrauma conditions, said that it has issued a call notice for the early exercise of warrants issued to investors on Oct. 26, 2010, Nov. 10, 2010 and December 3, 2010. Under the terms of the investor warrants, the company has the right to call for an early exercise when the company’s closing stock price equals or exceeds $2.80 per share for twenty consecutive trading days, which occurred on May 2, 2013. Since the start of April 2013, the company has already received $5.7 million from the exercise of investor warrants and expects to receive an additional $10.4 million from the early exercise of the warrants being called. On June 3, 2013, all Investor Warrants that are not exercised will be redeemed and the derivative warrant liability associated with the exercise or redemption of these warrants will be removed from InVivo’s books. This will eliminate a major impediment towards the uplisting of the company’s stock See Financings, Page 7

Medical Device Daily™ (ISSN# 1541-0617) is published every business day by AHC Media, 3525 Piedmont Road, Building Six, Suite 400, Atlanta, GA 30305, U.S.A. Opinions expressed are not necessarily those of this publication. Mention of products or services does not constitute endorsement. Medical Device Daily™ is a trademark of AHC Media, a Thompson Media Group, LLC company. Copyright © 2013 AHC Media. All Rights Reserved. No part of this publication may be reproduced without the ­written ­consent of AHC Media. (GST Registration Number R128870672) Atlanta Newsroom:

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To subscribe, please call Medical Device Daily™ Customer Service at (800) 477-6307; outside the U.S. and Canada, call (404) 262-5476. Copyright © 2013 AHC Media. Reproduction is strictly prohibited. Visit our web site at www.medicaldevicedaily.com.


Monday, May 6, 2013

Medical Device Daily™

Report from Europe

Eventus gets CE mark for Octava Pink cancer test A Medical Device Daily Staff Report

Eventus Diagnostics (Miami) has received CE mark designation for its Octava Pink breast cancer test intended for confirmatory use in women who have received negative mammography results. The National Cancer Institute (NCI) estimates that screening mammograms miss about 20% of breast cancers that are present at the time of the procedure, leading to false negative results. Studies suggest that the Octava Pink test confirms true negative mammography results with high accuracy, while identifying the presence of cancer in more than half of the cases when the mammography result is a false negative and cancer is actually present. Octava Pink is designed to reduce women’s concerns about missed cancers, while also enabling many of those with false negative results to seek follow-up care and when indicated earlier cancer treatment. Octava Pink is the first in a new class of rapid, accurate and cost-effective blood tests that measure disease-specific autoantibodies to detect the presence of cancer, the company said. EventusDx is partnering with breast cancer specialists in Italy and Israel to make Octava Pink available on a pilot basis. The Octava technology has been verified in clinical trials in over 800 women conducted at major cancer centers in Israel, Italy and the U.S. “We developed Octava Pink to address a serious shortcoming of mammography – the high rate of false negative results,” said Professor Benjamin Piura, MD, FRCOG, chief medical officer of Eventus Diagnostics and professor emeritus of obstetrics and gynecology at BenGurion University of the Negev. “The Octava technology has demonstrated encouraging specificity and sensitivity levels in multi-site clinical testing in over 800 women. We expect that Octava Pink will identify at least half of all breast cancers in women who were mistakenly given negative mammography results, while providing welcome reassurance to women whose negative results are accurate.” The Octava Pink test requires only a small sample of patient plasma to rapidly and cost-effectively determine disease status. It uses proprietary algorithms developed by EventusDx scientists to assess disease-specific autoantibody status.

Brainlab offers Novalis in Ireland Brainlab (Dublin, Ohio) said for the first time in Ireland, cancer patients can receive its Novalis Radiosurgery treatment, with the opening of the Stereotactic Unit at St. Luke’s Radiation Oncology Centre at Beaumont Hospital (Dublin).

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The Novalis Radiosurgery technology makes it possible for doctors to treat patients with many types of tumors including cranial, spinal, head & neck, lung, liver and prostate as well as arteriovenous malformations and trigeminal neuralgia. Combining a highly precise patient positioning system with sophisticated treatment planning software, the Novalis Radiosurgery technology helps clinicians destroy cancerous cells while helping to protect surrounding healthy tissue, Brainlab said. The company added that its Novalis Radiosurgery offers an alternative or complement to other therapies. More than 300 hospitals worldwide use Novalis Radiosurgery and benefit from the experience of over a million treatments. The Program provides patients across the globe access to what has become a standard in radiosurgery and stereotactic body radiation therapy.

Elixir to present DESolve results at EuroPCR Elixir Medical (Sunnyvale, California) said it will release six-month pivotal, clinical trial results for its fully bioresorbable drug-eluting scaffold system, the DESolve Bioresorbable Coronary Scaffold, on May 21, at the EuroPCR session of “From Late Breaking Trial to Clinical Practice” in Paris. The multi-center, prospective DESolve Nx Trial was See Europe, Page 5

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To subscribe, please call Medical Device Daily™ Customer Service at (800) 477-6307; outside the U.S. and Canada, call (404) 262-5476. Copyright © 2013 AHC Media. Reproduction is strictly prohibited. Visit our web site at www.medicaldevicedaily.com.


Monday, May 6, 2013

Medical Device Daily™

Agreements/contracts

SonaCare partners with UCL for new HIFU Center A Medical Device Daily Staff Report

SonaCare Medical (Charlotte, North Carolina), a specialist in minimally invasive HIFU technologies, has partnered with University College London (UCL) to create a HIFU Center of Excellence. The Center of Excellence will provide physician training and proctoring along with clinical studies, patient satisfaction research and advanced technology development associated with two HIFU systems: the Sonatherm laparoscopic HIFU surgical ablation system and the Sonablate 500 transrectal HIFU surgical ablation system. “Our collaboration with SonaCare Medical’s innovative technology provides a great platform for us to help expand the use of HIFU in a responsible and effective way. Tissue preserving strategies have been used successfully in other solid organ cancers, such as kidney cancer with great results. Published results from our practice continue to demonstrate that focal therapy delivers good cancer control along with a significant reduction in treatment side effects, which suggests a new option in a spectrum of prostate cancer care that, based on risk profile, can effectively balance clinical benefits and quality of life,” said Mark Emberton, MD, Director of the Division of Surgery and Interventional Science, University College London. UCL researchers presented multiple abstracts highlighting the ability of HIFU to balance disease control and quality of life at the recent European Association of Urology (EAU) Congress, including ongoing results from the UK Focal Therapy Study published in Lancet Oncology. In this study, UCL researchers evaluated the outcomes in men with multi-focal disease in which patients received focal HIFU therapy delivered to clinically significant cancer lesions using the Sonablate 500, developed by SonaCare Medical. In other agreements/contracts news: • Positron (Chicago), a nuclear medicine healthcare company specializing in the field of cardiac Positron Emission Tomography (PET) imaging and pharmacy automation, reported a co-marketing agreement with Biologics Modular (Brownsburg, Indiana). Biologics Modular makes modular facilities that serve as selfcontained biorepositories, biomanufacturing suites and research suites. “As we look to accelerate PosiRx adoption to markets both within and outside of the U.S., this collaboration is an innovative way reach an expanded targeted audience,” said Positron’s COO Charles Conroy. “PosiRx provides its users the ability to create patient specific unit doses in an ISO Class 5 environment and aids in compliance with USP

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797 regulations. For those customers that need additional cleanroom capacity, such as pharmacies providing custom compounding of cancer treatment therapies, Biologics Modular has the most comprehensive and cost effective solution on the market today. By decreasing start-up time and reducing operational costs, the combined solution allows new markets to be serviced sooner, and more profitably, than previously possible,” Conroy added. • Ultrasound-Images.com (Kerala, India) reported a marketing and distribution partnership with UBM Medica (Norwalk, Connecticut). Ultrasound-Images. com offers an extensive, free online gallery of highresolution, ultrasound, color Doppler, and 3-D images shared by medical professionals. UBM Medica is a media company serving the healthcare industry and delivering integrated and strategic communication solutions to a comprehensive audience of medical professionals and healthcare consumers through online, print, live, and custom programs. “Ultrasound-Images was created to allow the sharing of high-quality ultrasound images between colleagues and medical professionals throughout the world. We look forward to building upon our strong American following through distribution to UBM Medica’s comprehensive network of medical professionals,” said Joe Antony of Ultrasound-Images. Ultrasound-Images.com’s gallery of medical images reaches a global audience of up to 5,000 visitors per day and receives more than 200,000 page view each month from visitors in the U.S. Each image is labeled with a short description and useful links leading to quality information and images – and where required, this site also contains high-resolution ultrasound videos. In other agreements/contracts news: • Aeroflow Healthcare (Asheville, North Carolina) has been named among the top contract suppliers in the country for the Medicare DMEPOS (Durable Medical Equipment, Prosthetics, Orthotics and Supplies) Competitive Bidding Program. This program is an essential tool to help Medicare set appropriate payment rates for DMEPOS items while also saving beneficiaries and taxpayers money. Aeroflow Healthcare won 456 bids, meeting and exceeding even the largest players in the industry. AeroFlow Healthcare patients will benefit from Medicare’s bidding process as neither their provider nor current services will change. • The Premier (Charlotte, North Carolina) healthcare alliance reported new agreements for orthopedic power tools have been awarded to Brasseler (Savannah, Georgia); ConMed Linvatec (Largo, Florida); and Stryker Sales Corp., acting through its Instruments Division (Portage, Michigan). Premier operates a purchasing network and maintains clinical, financial and outcomes databases. n

To subscribe, please call Medical Device Daily™ Customer Service at (800) 477-6307; outside the U.S. and Canada, call (404) 262-5476. Copyright © 2013 AHC Media. Reproduction is strictly prohibited. Visit our web site at www.medicaldevicedaily.com.


Monday, May 6, 2013

Medical Device Daily™

Restructuring roundup

Hamonetics moving its Braintree manufacturing facility to Mexico A Medical Device Daily Staff Report

Blood management systems provider Haemonetics (Braintree, Massachusetts) said it will close its Braintree plant and move manufacturing of disposable products to its facility in Mexico. The company said in its earnings report Wednesday that it is in the process of transitioning its manufacturing of equipment to a contract manufacturer and transferring manufacturing of its disposable products from Braintree to Tijuana, Mexico. The move, which will take place over the next 12 to 18 months, will mean 320 job cuts, Haemonetics said. The decision comes after Haemonetics acquired the business assets of the blood collection, filtration and processing product lines of Pall (Port Washington, New York) (Medical Device Daily, August 3, 2012). It paid $555 million for the assets, which included facilities in Covina, California; Tijuana, Mexico; Ascoli, Italy and a portion of Pall’s assets in Fajardo, Puerto Rico. About 1,300 employees were transferred to Haemonetics.

Europe

Continued from Page 3 designed to enroll 120 patients at 15 centers in Germany, Belgium, Poland, Brazil and New Zealand. The primary safety endpoint of the DESolve Nx trial is the composite of major adverse cardiac events (MACE) comprised of cardiac death, target vessel myocardial infarction (MI) and clinicallyindicated target vessel revascularization (TLR). The primary angiographic endpoint of the trial is in-scaffold late lumen loss at 6 months as assessed by QCA (quantitative coronary angiography). Elixir Medical makes drug-eluting stent systems and bioresorbable coronary scaffolds.

AxoGen gets CE mark for AxoGuard products AxoGen (Alachua, Florida) reported CE mark approval for two of its nerve repair products, AxoGuard Nerve Protector and AxoGuard Nerve Connector. AxoGuard Nerve Connector and AxoGuard Nerve Protector are derived from a porcine submucosa extracellular matrix. The AxoGuard Nerve Connector is a coaptation aid for tensionless repair of severed nerves and the AxoGuard Nerve Protector is used to wrap and protect injured peripheral nerves and reinforce coaptation sites while preventing soft tissue attachments. AxoGen will use its existing distribution partners in Europe to sell the products. The AxoGuard Products are complementary to AxoGen’s Avance Nerve Graft, the only commercially available processed nerve allograft for bridging nerve

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Haemonetics continues to change its manufacturing footprint. In addition to halting manufacturing in Braintree, the company said it will be expanding its facility in Tijuana and building a facility in Asia. The company plans to keep its headquarters and have a center for excellence and research in Massachusetts. The plan is to hire 100-plus engineers and scientists. The company is still hammering out details of whether that will be in Braintree or somewhere else south of Boston, and is still deciding whether to combine the headquarters and the center for excellence in one location. In addition to announcing the cuts, Haemonetics said that on April 30, it completed the acquisition of the assets of Hemerus Medical, a Minnesota-based company that develops innovative technologies for the collection of whole blood and for the processing and storage of blood components. Haemonetics has, so far, paid $24 million of the total $27 million cash purchase price. In other restructuring news, Medtronic’s (Minneapolis) Spinal unit in Memphis will cut 60 local positions in a previously reported company-wide cost cutting plan. Medtronic Spinal has a local workforce of about 1,300. The Memphis layoffs are part of a plan to cut costs by 5%. Medtronic said that employees who have been laid off could apply for other positions in the company. n discontinuities (gaps created when nerves are severed), which is available in the U.S., Canada, Austria, Italy and Switzerland.

CellAegis starts European autoRIC trail CellAegis Devices (Toronto) reported the first clinical trial program in the European Union to evaluate the use of the company’s autoRIC Device for Chronic Remote Ischemic Conditioning (CRIC). In the DREAM study (Daily REmote Ischemic Conditioning following Acute Myocardial Infarction), a University of Leicester-sponsored Phase II, randomized, placebo-controlled clinical study, CRIC will be evaluated for its ability to prevent negative remodeling of the heart in patients following an acute myocardial infarction. A quarter of patients suffering a heart attack show symptoms of heart failure at the time of admission, and CRIC has the potential to interrupt this disease process. CellAegis’ autoRIC Device is intended to reduce tissue injury from heart procedures or heart attacks in a hospital or ambulance setting or in the home as directed by a healthcare professional. Remote ischemic conditioning uses sequences of short, controlled periods of blood occlusion (ischemia) in a limb followed by resumed blood flow (reperfusion). By activating innate mechanisms of metabolic protection in the body, RIC has been shown to reduce the larger injury from ischemia reperfusion to heart and other organs, including myocardial infarctions, cardiac surgery, stroke, trauma, and organ transplantation. n

To subscribe, please call Medical Device Daily™ Customer Service at (800) 477-6307; outside the U.S. and Canada, call (404) 262-5476. Copyright © 2013 AHC Media. Reproduction is strictly prohibited. Visit our web site at www.medicaldevicedaily.com.


Monday, May 6, 2013

Medical Device Daily™

Deals roundup

Zimmer to acquire business assets of Knee Creations A Medical Device Daily Staff Report

Zimmer Holdings (Warsaw, Indiana) said that it has acquired the business assets of Knee Creations (West Chester, Pennsylvania). The acquisition enhances Zimmer’s product portfolio of knee treatments through the addition of Knee Creations’ Subchondroplasty procedure. Subchondroplasty is an innovative, proprietary joint-preservation treatment that has been shown to deliver sustained relief to patients with knee pain, with or without arthritis. It is the first procedure to address an unmet clinical need between early interventions, including NSAIDs and arthroscopy, and total joint replacement. “Zimmer is committed to developing the most comprehensive range of therapies for knee patients, from early intervention and joint preservation products to patient specific instrumentation and personalized joint replacements,” said Jeff McCaulley, president, Zimmer Reconstructive. “The acquisition of Knee Creations’ revolutionary Subchondroplasty treatment provides Zimmer with another clinically differentiated offering that addresses an unmet clinical need.” Marc Viscogliosi, a founder and chairman of Knee Creations board, said, “On behalf of the Knee Creations board and its whole investor base, we are pleased that Zimmer will be the new owner of this business and technology, enabling it to further flourish for the benefit of patients and physicians. As a global leader, we believe Zimmer can make the greatest impact with the revolutionary Subchondroplasty procedure platform.” Subchondroplasty is a percutaneous outpatient intervention that addresses the defects associated with subchondral bone marrow edema (BME). BMEs are related to stress fractures or micro-fractures and are diagnosed using MRI. Left untreated, these defects have been shown to lead to cartilage degeneration, limited function, pain and greater risk for joint deterioration. According to Larry Biegelsen, a senior analyst with Wells Fargo, the market opportunity for subchondroplasty is fairly modest and the acquisition could help drive market growth. “Our industry contacts suggest there are about 1 million patients with knee pain who are being conservatively managed,” Biegelsen wrote in a research note. “Assuming an average ASP between vertebroplasty ($2,000) and kyphoplasty ($4,000), implies that sales of Subchondroplasty have been around $5 million to date (1,500 x $3,000). We could envision sales of Subchondroplasty for Zimmer in the range of $5 million to $10 million in 2012, increasing to $20 million to 30 million in 2014. Our understanding is that reimbursement

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is already in place and is favorable under the coding pathway of arthroscopically assisted fracture repair for the tibia or femur. Although we have not confirmed this with Zimmer, we would expect the company to book sales of Subchondroplasty in their knee line as they are currently doing with Gel One. Therefore, the acquisition of Knee Creations combined with the launch of Gel One and their new Persona knee, should help drive above market knee growth for the next few years in our view. 

HIT roundup

GenomeDx launches iPad urology app, UroSketch 3D A Medical Device Daily Staff Report

GenomeDx Biosciences (San Diego and Vancouver, British Columbia) has launched an application for the iPad, available in the Apple App Store, called UroSketch 3D. The app, which provides a 3-D model of the prostate, bladder and surrounding organs for use by physicians during consult with their patients, works with any iPad and iPad mini using the iOS 6 software. UroSketch 3D was developed in collaboration with Conquer Mobile (Vancouver) and a panel of urologists and consists of preset three-dimensional model views, which allow a physician to zoom in on an image and show the image in 360-degree rotation. The application also offers illustration of different tumor stages and other features which currently focus on the prostate. The project was funded with a grant from the Industrial Research Assistance Program (IRAP). In each view in the UroSketch 3-D app, physicians can use a draw and/or highlighter function to mark up images and then email or print out a personalized PDF for patients to take home. The resulting PDF will include a header with physician name, date stamp and any contact details that the physician provides upon download of the app. Consult sessions are listed on the home screen by time and erased at the end of each day to ensure privacy. Physicians may create master sketches, which are not erased and can be used as templates for new sessions. “The initial conversation when I first tell my patient that he has prostate cancer can be very challenging for both of us. The weight of the news makes it very difficult for him to absorb new information about his prostate cancer and any details regarding management options to follow,” said Ali Kasraeian, MD, of Kasraeian Urology (Jacksonville, Florida). “I think this app will help engage the patient in his personalized prostate cancer conversation and help facilitate better communication and more effective patient understanding, especially since I can send patients home with an image that will reinforce the details of our conversation.” n

To subscribe, please call Medical Device Daily™ Customer Service at (800) 477-6307; outside the U.S. and Canada, call (404) 262-5476. Copyright © 2013 AHC Media. Reproduction is strictly prohibited. Visit our web site at www.medicaldevicedaily.com.


Monday, May 6, 2013

Insulet

Medical Device Daily™

Continued from Page 1 ‘how do you use U-500 in the pump and how do you dose it and is it safe to do?’ And the problem with answering that question is that it has not been approved for use in a pump, but everybody’s using it off label.” Bode is a diabetes specialist with Atlanta Diabetes Associates and is a clinical associate professor in the Department of Medicine at Emory University (Atlanta). And because one unit of U-500 is as powerful as five units of U-100, both doctors and patients have to be extra careful that they are giving the correct amount of U-500 whether they are putting it in a pump or a syringe. “So when people go to U-500 either in a syringe or in a pump, you have to do all of these calculations. One, you have to do it for the patient if you’re putting it in a pump, so you’re fudging everything by five times,” Bode told Medical Device Daily. “ . . . That can create a lot of errors.” To address this problem, Insulet (Bedford, Massachusetts), a company known for its tubeless insulin pump technology, has entered into an agreement with Eli Lilly to develop a new version of the OmniPod insulin pump specifically to deliver Humulin R U-500 insulin (Medical Device Daily, May, 3, 2013). This new version of the OmniPod System would be the first insulin pump designed with specific feature modifications to deliver Humulin R U-500 insulin. “This is a huge step forward . . . it will allow patients to give high-dose insulin in a safe and effective manner,” Bode said. “This will be very good for patients who are markedly insulin resistant and it will be very good for healthcare providers because they don’t have to be doing these calculations.” Insulet said it will partner with Eli Lilly on the clinical development program to evaluate the safety and efficacy of the combined delivery system. “We are pleased to develop the first insulin pump specifically for Humulin R U-500 insulin to bring the advantages of the OmniPod System to people with highly insulin resistant Type 2 diabetes,” said Duane DeSisto, president/CEO of Insulet. “The tubeless design of the OmniPod insulin pump provides freedom and ease of use for tens of thousands of people living with diabetes today.” Late last year, Insulet reported FDA 510(k) clearance for its second-generation OmniPod system (Medical Device Daily, Dec. 17, 2012). In a conversation with MDD following the FDA clearance, Insulet CFO Brian Roberts said the new OmniPod is the equivalent of the newest generation iPod compared to an old eight track cassette player or vinyl record player. The OmniPod system is the world’s first tubeless insulin pump. It consists of a Pod, which automatically inserts and can be worn on many parts of the body to hold and deliver insulin, and a hand-held device that wirelessly programs the Pod, calculates suggested doses and has a built-in blood

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glucose meter. Importantly, the system is also tubeless and waterproof, Roberts noted. The company introduced the first generation of the device in 2005. Humulin R U-500 is indicated as an adjunct to diet and exercise to improve glycemic control in adults and children with Type 1 and Type 2 diabetes mellitus. “I think this is going in the right direction to make insulin safer and U-500 is not as safe in ordinary practice because you have to do these reverse calculations and people can make very dangerous mistakes,” Bode said. “The FDA has stated that they will not approve any new concentrated insulin that is coming out unless it’s in a dedicated delivery device.” Other options for insulin-resistant diabetes patients, other than the U-500 insulin, include bariatric surgery and GLP-1 (glucagon-like peptide 1) drugs, or a low-calorie diet, which is defined as less than 800 calories a day. The primary treatment option for this patient population, Bode said, is bariatric surgery but not everybody wants to undergo surgery and patients have to have a body mass index (BMI) greater than 35 (but, he noted, most surgeons prefer the patient have a BMI greater than 40). As for the other non-insulin treatment options, Bode said compliance is a problem with both the low-calorie diet and the GLP-1 drugs. n Amanda Pedersen, 912-660-2282; amanda.pedersen@ahcmedia.com

Financings

Continued from Page 2 to a national securities exchange. The company is also terminating its previously reported offer to exchange with respect to the investor warrants only. • DocuTAP (Sioux Falls, South Dakota) said that has raised $1 1 .9 million from Bessemer Venture Partners to make sure that if something does go wrong, it is not the result of disorganization. DocuTAP helps urgent care clinics digitalize their operations to make them more efficient and less reliant on paper. The software integrates electronic health records and “practice management” technology so all the information and tools needed to operate an efficient practice is one place. The platform is accessible on tablets so clinicians can use it on-the-go. DocuTAP also features automated and customizable tools so each clinic can tailor the software to their needs as well as billing services. 

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Monday, May 6, 2013

Medical Device Daily™

MTI

Continued from Page 1 purpose,today, a drainage tube (shunt) is introduced into the eye to reduce such pressure (such as, for example, Alcon’s (Fort Worth, Texas) product that it purchased from Israeli company Optonol in 2009 for more than $150 million). While a truly inventive product, the implantation of today’s shunts often lead to an excessive reduction in intraocular pressure, with resultant side effects, explained Rheon’s founder Nikolaus Stergiopulos PhD. “Persistent hypotony – where low ocular pressure leads to choroidal detachmentand other serious complications – is reported to occur in 10%-30% of these implanted cases” he told MDD. Often, a second operation is required. To improve this generation of shunts, Rheon is developing an adjustable shunt, based on technology developed in Lausanne’s Ecol Polytechnique (EPFL). Using sub-millimeter components in its proprietary adjustable shunt, Rheon has developed its “micro-tap”, an externally controlled implant, with which the physician can gradually increase the tube’s aperture, and hence offer a more controllable intraocular pressure. In many ways, this is Swiss-watch technology in a medical environment. “We could not be in a better region for micro-mechanics,” he explained, “and there are few sites worldwide that could design the sub-millimeter elements in our system, to the precision and quality that the product needs. The BioAlps region is perfect for that.” Having recently completed animal studies using the implant, the company has completed its immediate capital raising requirements. “This funding will take the product through CE, initial clinical study, CE and ‘soft’ market launch, which should take us through to mid 2014,” said Stergiopulos, “and enable high quality clinical work here in Lausanne” he added. In addition to this improved glaucoma implant, a couple of retinal tissue ablation technologies were also presented at the startup conference. These companies have generated products that aim to treat retinal diseases in a more effective, and less demanding manner than available to date. OD-OS is a German-U.S. company focusing on major retinal diseases that require inhibition of angiogenic growth in the eye. The company has developed the Navilas Laser System to accurately map and then coagulate the specific spots on the retina where microaneurisms have developed and result in damage to vision. By using the system, the company says, the ophthalmologist is able to work in a highly focused and discriminating fashion, so that the relevant sub-millimeter aneurisms can be coagulated with limited collateral damage. The company of 30 employees was started by CEO Winfried Teiwes PhD, who was previously the founder of SMI(Berlin), a company whose ophthalmic business, focusing on ocular surgery guidance, was bought in late

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2012 by Alcon. Over 30 Navilas systems are available worldwide in Europe, U.S. and parts of Asia, primarily for Diabetic Macular Edema (DME), Proliferative Diabetic Retinopathy (PDR) and potentially for other retinal diseases involving excessive retinal blood vessel growth that cause such aneurysms. The system enables the use of previous data (fusing of OCT or optical/fluorescence images) or on-the-spot imaging, followed by a few moments of physician laser planning, to design the optimal patient laser treatment. Based on the SMI’s skills in eye image registration, and ODOS’ planning techniques, a precise, complete and rapid laser coagulation is executed in seconds. “The advantage offered by our product,” described Teiwes, “is that this precise, rapid approach reduces the physician’s error in laser application, which – especially in macular treatments – has grave consequences for the patient. Our system reduced error rate significantly and invariably offers a quick and more complete treatment in a single session – resulting in a faster stabilization of disease.” OD-OS is raising about $7 million for expansion distribution channels, and coordinating reimbursement, and expansion into Asia, especially the Japanese, Chinese and Korean markets. Another advanced company in the retinal treatment field, but this time with major focus on wet AMD, is Oraya Therapeutics (Newark, California). Wet AMD is characterized by excessive growth of (leaky) blood vessels in the retina, and is today generally treated using VEGF inhibitor drugs. The company utilizes the fact that the cells in the patient’s eye that are causing this damage tend to be growing fast, much like cancer cells. As a result, Oraya treats these cells with a modality similar to that used with cancer patients to arrest growth: a one-time modified X-ray radiotherapy regimen. “We realized that the ability to reduce – and in many cases to eliminate – the need for expensive and painful anti-VEGF intro-ocular injections, would be a game changer,” related CEO Jim Taylor, formerly both CEO of Carl Zeiss Meditec (USA), and board member of Carl Zeiss Ophthalmics (Jena, Germany). “We have been pleased with the results of the INTREPID (sham control double blinded) trial that were recently published, online in the leading peer-reviewed journal Ophthalmology, which showed a good safety profile as well as effective reduction in antiVEGF injections”. Taylor told MDD that in about 30% of a significant sub-group of patients who received the macular X-ray treatment, blood vessel growth was inhibited that to the level that not a single VEGF injection was required by the patient at 12 months, and in almost all cases, for this subgroup, significant reduction in injections during the 12-month trial were observed. With robust clinical data in hand, the company is now planning to initiate European sales, based on a CE received in early 2010. “With this data supporting us, we are now See MTI, Page 9

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Monday, May 6, 2013

Capital

Medical Device Daily™

Continued from Page 1 made its mission showing up at the near-outset of promising science. “We provide the nondilutive form of capital that’s less expensive than equity, but because it’s less expensive, we’re also looking to take less risk than equity, and so we come in at the later stage,” Düster said. “[With] large pharmaceutical companies, the partnership activity gets later and later stage,” he said. “Big pharma folks used to take earlier risk on big up-front payments for preapproval, but now the big up-fronts and the big partnerships have been after you’ve been able to show a little bit of [commercial] success.” Capital Royalty Partners II already has closed on six investments, with a seventh in the works. “We have more deals in our pipeline than we can complete,” Düster said. In general, Capital looks for an approved product with strong intellectual property and potential for growth in its therapeutic area. “Cancer is 50 percent of the market, and so you have to always be looking at cancer drugs,” Düster said. “One of our earlier investments, which is undisclosed, is in a leading cancer drug, so it’s an area of expertise for us and an area of interest to us.” As drug approvals become more challenging, Capital finds “more opportunities popping up” in devices and diagnostics, as well as delivery technologies, he said. “We expect that trend to continue. I would not say that [drug investment prospects] are harder to come by, but we want to look at best in class products, and drugs are not the only section of the market,” Düster said. In early February, Capital closed a term-loan facility with TriVascular (Santa Rosa, Caliornia), the second fund’s largest commitment so far. TriVascular develops endovascular aortic repair (EVAR) stent graft systems for aortic aneurysms. Late last year, the FDA approved TriVascular’s Ovation and Ovation Prime systems for abdominal aortic aneurysms, “an increasing problem in the U.S.,” Düster said. The market for EVAR stent grafts continues to enlarge, too, because they are replacing open-heart surgery and other surgical procedures, he noted. Diabetes is another area of interest for Capital, Düster said, as well as the smaller or mid-cap companies developing orphan drugs. “Because they are going after a specialized therapeutic area, they don’t need to have a 200-person sales force,” said. “They can do it on a much smaller scale,” with help from Capital. “We see more than 100 opportunities per year,” Düster said, but the firm aims to close on four to six. “Most of it, you can imagine, is going to be easy sifting, because many companies hear that you have money, and they are years away from approval,” he said. “Many others are very good companies, but are either too early or the market is too complex to really understand potential market share and

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potential revenue.” The evolving big pharma business model has created a “tailwind for the royalty market,” said Clarke Futch, founder and managing director of HealthCare Royalty Partners, during a BioWorld/Medical Device Daily webinar Thursday, titled “Royalty Financing for Biotech and Medical Device Companies: How to Determine Eligibility and Take Advantage of this Unique Financing Opportunity.” Calling royalty sales “simply one option to raise capital,” Futch said it’s one that has proved especially useful lately. “The addressable size of the market in terms of dollars available in royalties has grown dramatically over the last five to 10 years,” he said. “You have more royalties out there to be bought, and higher royalty rates.” With casualties falling off the patent cliff and continued pressure to grow top-line sales, “royalty rates have gone up as large pharma has competed to in-license products to fill this product gap,” Futch said. As long ago as the first part of the 1990s, pharma companies began to buy back their own royalties, but it was not until the late 1990s and early 2000s that “a couple of boutique firms focused on buying royalties, initially from universities and inventors, but very soon thereafter, [began] approaching biopharma companies and medical devices companies about purchasing their royalty streams as a way of financing.”n

MTI

Continued from Page 8 comfortable placing eight systems throughout Europe, including in UK, Switzerland and Germany. To reduce some, if not all, of the required eye injections, is a great benefit for patients, physicians and payors”, Taylor told MDD. Once this European expansion is underway, Oraya may approach the massive Asian AMD market. In Asia, photodynamic therapy is often used in conjunction with anti-VEGF treatment, Oraya told MDD. “We feel that this market is very attractive for us, based on the form of the disease prevalent in the Asian population.” Oraya has raised $70 million to date from a wide range of well-known medical technology investors, including Domain Associates (San Diego) and Essex Woodlands (Palo Alto, California). It is now planning a $40 million round for commercialization purposes, with current investors planning to participate in the round. n Access Medical Device Daily Archives Online! You have FREE access to articles dating back to 2005 — perfect for company research or for finding supporting data for presentations and reports. Go to www.MedicalDeviceDaily.com for access.

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Monday, May 6, 2013

ExThera

Medical Device Daily™

Continued from Page 1 into the cost of sepsis care. ExThera Medical (Berkeley, California) took part in a special presentation titled Medtech Matters: Emerging, Game-Changing Technologies, which was hosted by Ronald Trahan Associates. ExThera CEO Robert Ward spoke on behalf of the company and discussed the need for its Seraph (Selective Removal by Apheresis) affinity therapy device in the sepsis treatment market. “The inappropriate use of many [antibiotics] has caused many pathogens to evolve and become drug resistant,” Ward said during the presentation. “In addition the sole process of pathogen identification can delay the start of treatment. This is critical because it’s well established that delayed treatment increases mortality. It follows that a broad spectrum therapy that reduces the intensity and duration of a blood stream infection is needed. We expect [Seraph] to halt progression of septic shock, saving lives; and reducing the need for expensive ICU care.” He added that initially the company said it plans to use Seraph to prevent sepsis and the organ failure that can result. “But in the future, we expect that Seraph will be proven useful in the treatment of more advance stages of the disease where few if any treatments are currently available,” Ward said. Seraph is a cartridge-shaped device containing tiny beads coated with heparin, an anticoagulant. The heparin sifts through the blood, removing bacteria or cytokines — excess proteins and peptides found in the blood — which can lead to infection or sepsis. In combination with the current standard of care, ExThera said that its device could allow therapy to be started at the earliest sign of bloodstream infection. This rapid approach to treatment without a forty-eight to seventytwo hour delay in pathogen identification should reduce the duration of bacteremia, the incidence of dangerous metastatic infections and the cost of patient care. The first clinical indication will be in end stage renal disease patients with S. aureus and MRSA infections where it will be used in series with a hemodyalizer during a three to five hour treatment session. ExThera said that it hopes to receive a CE mark by the end of 2013. “The initial clinical trial will be a pilot clinical trial with five patients and the goal of that trial is to take a safety and effectiveness measurement,” he said. “In terms of effectiveness, we’re looking for a change in bacterial load. In terms of safety we’re looking for changes in hematology indices...; changes in chemistry indices; any change in the incidents of adverse events; and the incidents of device complications. Those will be primary endpoints.” “In terms of secondary endpoints, we’re looking for

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more detail in terms of the effectiveness of the device,” he said. “The rate of cardiac and non cardiac infectious complications will be monitored. Changes in cytokine levels will be monitored. All clinical and laboratory adverse events will be monitored too.” The pivotal clinical will be expanded to 60 to 100 patients and will be modified somewhat based on the results of the initial pilot clinical trial. Plans call for the firm to conduct clinical trials in the U.S. starting in 2014. ExThera was formed through a joint venture between the Emergence Venture Partners (a Life Science incubator) and ExThera AB of Stockholm in 2008. To date it has raised nearly $15 million. Ward said that the company is seeking a Series B round of financing.  Omar Ford; 404-262-5546; omar.ford@ahcmedia.com

People in the News • Colorado BioScience Association (CBSA; Denver) has named Derek Cole, President of Investor Relations Advisory Solutions, Broomfield & New York, as the new chairperson of its board of directors. The CBSA is a notfor-profit organization providing services and support for Colorado’s bioscience industry. • The board of the TriZetto Group (Denver) reported a reorganization of the leadership team. Trace Devanny will be leaving the company, effective immediately, to pursue other opportunities. An executive search is underway for a permanent CEO. As part of these changes, Vicky Gregg, a member of TriZetto’s board since 2008, will assume the role of non-executive chair and will actively support the company’s leadership team. Gregg was previously CEO of BlueCross BlueShield of Tennessee. Jude Dieterman, who currently serves as executive VP and COO of TriZetto, has been named to the newly-created role of president. TriZetto provides information technology and service solutions that help payers and providers work more efficiently and collaborate to deliver better health.

Advertise Here ...and reach high-level med-tech professionals every day! For advertising opportunities in Medical Device Daily, please contact Stephen Vance at (404) 262-5511 or stephen.vance@ahcmedia.com

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Monday, May 6, 2013

Medical Device Daily™

Product Briefs • Alpinion Medical Systems (Bothell, Washington) has introduced its lightweight, portable E-Cube 7 ultrasound system for use in guidance during regional anesthesia and pain medicine procedures. Alpinion’s E-Cube philosophy focuses on Ergonomic Design, Efficient Workflow and Excellent Image Quality. The E-Cube 7 is designed to cover a wide range of clinical applications and is ideally suited for ultrasound-guided regional anesthesia, pain medicine and musculoskeletal. • CryoXtract Instruments (Woburn, Massachusetts) reported the launch of its CXT 350T Frozen Tissue Aliquotter. The CXT 350T allows for targeted, repeated and safe access to frozen tissue samples, while preserving their frozen state throughout the entire process. The CXT 350T’s proprietary coring process enables uniform sizing and efficient distribution of frozen tissue sample aliquots, thereby maximizing sample integrity and optimizing scientific outcomes, the company said. R • DePuy Orthopaedics (Warsaw, Indiana) received Pre-Market (PMA) Supplement Approval from the FDA for the DePuy Ceramax Total Hip System with Biolox delta Ceramic-on-Ceramic 36 mm Large Femoral Head. This PMA supplement approval for the 36 mm size follows the initial PMA approval of the Ceramax Hip 28 mm size in 2010. The key benefits of Biolox delta Ceramic Head are its very high strength and toughness. These properties are achieved as a result of the high density of the material and the very small grain size of the alumina matrix, DePuy said. • Olympus (Center Valley, Pennsylvania) reported the commercial availability of its 510(k) cleared BF-190 bronchoscopes. The new BF-190 bronchoscopes offer unparalleled maneuverability and flexibility through the combination of their unique Rotary Function and wider tip angulation, which will potentially allow physicians to access areas of the lung that may not be easily reached with current generation bronchoscopes. The Rotary Function is estimated to reduce hand torque by up to 82% which may translate to a significant reduction in hand fatigue and injury. • SonaCare Medical (Charlotte, North Carolina), a specialist in minimally invasive high intensity focused ultrasound (HIFU) technology, said it will launch the FDA-Cleared Sonatherm HIFU Surgical Ablation System at the the 108th Annual Meeting of the American Urological Association (AUA), in San Diego, May 4-8. A laparoscopic HIFU surgical ablation system, Sonatherm is cleared for the laparoscopic or intraoperative ablation of soft tissue. Sonatherm uses HIFU energy to ablate a wide variety of soft tissues from the ultrasound focal point back to the surface of the targeted tissue. • Valeritas (Bridgewater, New Jersey), makers of the V-Go insulin delivery device, reported new interim analysis from an observational study that suggest patients with

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ODAC: Delcath’s Melblez gets unanimous unfavorable vote

A Medical Device Daily Staff Report Delcath Systems (New York) said the FDA’s Oncologic Drugs Advisory Committee (ODAC) voted 16 to 0 with no abstentions that benefits of treatment with Delcath’s Melblez Kit (Melblez for Injection for use with the Delcath Hepatic Delivery System) for the treatment of patients with unresectable ocular melanoma metastatic to the liver do not outweigh the risks associated with the procedure. The system performs what Delcath calls chemosaturation, using the device to inject a high dose of the chemotherapy melphalan to the liver. In clinical studies, eight people, almost 7%, died from adverse reactions including liver failure, hemorrhagic brain lesions and gastrointestinal bleeding, FDA staff said April 30. Of the patients who received alternative care, none had fatal reactions. “Patients have very few treatment options,” Mikkael Sekeres, panel chairman and associate professor of medicine staff at the Cleveland Clinic’s Taussig Cancer Institute, said during the panel meeting. “Exposing them to a treatment that could kill them in the next month is not the right thing to do. The risks of this treatment far outweigh any benefit and they actually introduce harm.” The studies the panel considered today were based on an older filter and the company said it plans to use an upgraded filter in use in Europe if the product gains U.S. approval. Delcath didn’t immediately say if it would conduct a new study on the device. Patients who used the Melblez Kit in studies also experienced more serious adverse reactions, including a decreased ability of the bone marrow to make blood cells and liver toxicity, FDA staff said in their report ahead of the advisory panel meeting. The FDA is not bound by the recommendation of its advisory committee, but will consider the committee’s guidance as it evaluates the Melblez Kit New Drug Application (NDA). The Prescription Drug User Fee Act (PDUFA) goal date for completion of the FDA’s review and decision regarding approval of the Melblez Kit NDA is September 13, 2013. Type 2 diabetes who switched to the V-Go insulin delivery device from their previous baseline treatment experienced potentially significant improved glycemic control and a reduction in total daily insulin dose. The interim results, part of a planned interim analysis performed as part of a longterm, prospective, observational study, were presented at the American Association of Clinical Endocrinologists (AACE) 22nd annual scientific and clinical congress. V-Go is a fully-disposable device that delivers a continuous basal rate of insulin for 24 hours with on-demand mealtime dosing. It is designed to be easier to use and assist with blood glucose control in adult patients who require insulin.

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MDD’s Neurology Extra ADDITIONAL DEVELOPMENTS

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MONDAY, MAY 6, 2013

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Keeping you up to date on recent developments in neurology How are our brains wired? . . . A paper published in Frontiers in Human Neuroscience by Kunjumon Vadakkan, MD, is breaking new ground in the field of neuroscience. How are our brains wired? How does this wiring produce brain functions? Can we reproduce this wiring pattern outside the brain to develop artificial intelligence? Throughout the world, brain researchers are busy addressing these questions. The brain activity mapping project reported this month in the U.S. by President Obama is the latest example of these efforts (Medical Device Daily, April 8, 3013). The hope is that the large amount of data that will be obtained from these studies will unlock the mechanism of brain functions. Vadakkan at the University of Manitoba (Winnipeg, Canada) has made a complementary approach to the conventional brain activity mapping. According to him, in order to understand brain circuitry, a framework from basic mechanisms that can inter-link multi-level functions observed by different faculties of brain science is necessary. The semblance hypothesis proposed by Vadakkan in 2007 explains how internal sensations of the nervous system can evolve from synaptic and neuronal activities. This may be considered as the only way to understand the internal sensations which only the owner of the nervous system can access. This approach of viewing higher brain functions as virtual internal sensations has found success in explaining most of the key findings from different fields of brain sciences. This mapping method has rigorously tested its ability to explain long-term potentiation (LTP), consolidation of memories, place cell firing, different features of schizophrenia, and ability to build a framework for consciousness. According to Vadakkan, ability to build frameworks to explain most of the brain functions is sufficient proof that we can achieve the gold standard of replicating the proposed mechanism in physical systems. This is necessary for properly mapping the brain circuitry. Developing engineering tools to convert the first-person properties of the internal sensations to matching read-outs is required to map the functional brain circuitry, brain-mind interface and to develop artificial intelligence. Inter-postsynaptic functional LINKs, key building elements of the proposed neuronal circuitry matches with the K-lines proposed to build systems with memory by Marvin Minsky, co-founder of MIT’s AI laboratory. This brain activity mapping explores what constitutes the mind that stores memories, and remains conscious. The neuronal circuit that can explain a mechanism for the internal sensations is published in the paper titled “A supplementary circuit rule-set for the neuronal wiring.” Vadakkan has substantiated the functioning of the neuronal circuit and is hopeful that the proposed mechanism will hold up. Vadakkan says that publication of this paper is very timely and is hopeful that it will get tested during the brain mapping project. Will the hypothesis be proved true? According to Vadakkan, only time will tell; in science we need to challenge ourselves, remain optimistic, work hard and be patient. One thing is sure: testable hypotheses will bring lots of enthusiasm and hope to the brain mapping project.

Discovery studies alcohol/brain interaction . . . Thanks to a rare bacteria that grows only on rocks in the Swiss Alps, researchers at The University of Texas at Austin and the Pasteur Institute (Paris) have been the first to identify how alcohol might affect key brain proteins. It’s a major step on the road to eventually developing drugs that could disrupt the interaction between alcohol and the brain. “Now that we’ve identified this key brain protein and understand its structure, it’s possible to imagine developing a drug that could block the binding site,” said Adron Harris, professor of biology and director of the Waggoner Center for Alcohol and Addiction at The University of Texas at Austin. Harris and his former postdoctoral fellow Rebecca Howard, now an assistant professor at Skidmore College, are co-authors on the paper that was recently published in Nature Communications. It describes the structure of the brain protein, called a ligand-gated ion channel, that is a key enabler of many of the primary physiological and behavioral effects of alcohol. Harris said that for some time there has been suggestive evidence that these ion channels are important binding sites for alcohol. Researchers couldn’t prove it, however, because they couldn’t crystallize the brain protein well enough, and therefore couldn’t use X-ray crystallography to determine the structure of the protein with and without alcohol present. “For many of us in the alcohol field, this has been a Holy Grail, actually finding a binding site for alcohol on the brain proteins and showing it with X-ray crystallography,” said Harris. “But it hasn’t been possible because it is not possible to get a nice crystal.” The breakthrough came when Marc Delarue and his colleagues at the Pasteur Institute sequenced the genome of cyanobacteria Gloeobacter violaceus. They noted a protein sequence on the bacteria that is remarkably similar to the sequence of a group of ligand-gated ion channels in the human brain. They were able to crystallize this protein. Harris saw the results and immediately got in touch. “This is something you never would have found with any sort of logical approach,” he said. “You never would have guessed that this obscure bacterium would have something that looks like a brain protein in it. But the institute, because of Pasteur’s fascination with bacteria, To subscribe, please call MEDICAL DEVICE DAILY™ Customer Service at (800) 477-6307; outside the U.S. and Canada, call (404) 262-5476. Copyright © 2013 AHC Media. Reproduction is strictly prohibited. Visit our web site at www.medicaldevicedaily.com.


MONDAY, MAY 6, 2013

MDD’S NEUROLOGY EXTRA

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has this huge collection of obscure bacteria, and over the last few years they’ve been sequencing the genomes, keeping an eye out for interesting properties.” Harris and Howard asked their French colleagues to collaborate, got the cyanobacteria, changed one amino acid to make it sensitive to alcohol, and then crystallized both the original bacteria and the mutated one. They compared the two to see whether they could identify where the alcohol bound to the mutant. With further tests they confirmed that it was a meaningful site. “Everything validated that the cavity in which the alcohol bound is important,” said Harris. “It doesn’t account for all the things that alcohol does, but it appears to be important for a lot of them, including some of the ‘rewarding’ effects and some of the negative, aversive effects.”

Implanted device predicts epilepsy seizures . . .

For the first time, a small device implanted in the brain has accurately predicted the onset of seizures in some adults who have epilepsy and do not respond to drugs. The small proof-of-concept study is published today in The Lancet Neurology. ‘Knowing when a seizure might happen could dramatically improve the quality of life and independence of people with epilepsy and potentially allow them to avoid dangerous situations such as driving or swimming, or to take drugs to stop seizures before they start, rather than continuously as at present,’ said lead author Mark Cook from the University of Melbourne in Australia. The technology, developed by NeuroVista (Seattle), is designed to detect abnormal electrical activity in the brain that precedes a seizure using electrodes implanted between the skull and brain surface which constantly monitor electrical activity (electroencephalography or EEG) data. The electrodes are connected to a second device implanted under the skin of the chest which transmits this information wirelessly to a hand-held device that calculates the probability of a seizure. Three colored lights warn patients of the high (red), moderate (white), or low (blue) risk of an impending seizure. The Australian feasibility study included 15 people with focal epilepsy, a condition where seizures start in a specific part of the brain. Aged between 20–62 years, they experienced between two and 12 seizures per month and had not had their seizures controlled despite use of at least two anti-epileptic drugs. During the first month after surgical implant, the system was set for detection only while EEG data containing a minimum of five seizures was collected and analyzed to construct an individualized algorithm to predict the likelihood of a seizure. The researchers measured the system’s performance, clinical effectiveness, and safety for four months after implant and four months following activation. During the initial data collection, the system correctly predicted seizures with a ‘high warning’ sensitivity (the proportion of actual positives which were correctly identified) greater than 65%, and worked to a level better than chance in 11 of the 15 adults. In eight of the 11 patients who went on to have the device activated and to use the system for four months, sensitivity ranged from 56% to 100%. The technology is said to appear relatively safe, with a similar safety profile to other implanted devices such as deep brain stimulators for Parkinson’s disease. Three patients experienced serious device-related adverse events, with two requiring the device to be removed. The study revealed disparities between reported and detected events, with most participants underestimating the number of their seizures. One patient who reported having 1 1 seizures per month actually had 102. Cook is optimistic that if the findings are replicated in larger, longer studies, this technology will improve management strategies including developing methods of preventing seizures using direct electrical stimulation or fast-acting drug therapies.

Investigating devastating childhood diseases via skin cells . . .

Induced pluripotent stem cells (iPScs) from the skin of patients with Dravet syndrome (DS) show Dravet-like functional impairment when they are converted into neurons, finds research in BioMed Central’s (London) open access journal Molecular Brain. This method provides a non-invasive way to investigate diseases which affect the nervous system of humans. Research into genetic diseases like DS is hampered by its rareness. It affects 1 in 30,000 children and is first noticed within the first year or two or life. Seizures are hard to control and as the child develops other neurological problems emerge meaning that most will require help and support throughout life. About 70-80% of people with DS have a mutation in their SCN1A gene which disrupts normal function of voltage-gated sodium channels in the brain. This mutation is normally not inherited from either parent but is unique to the affected child. Research models of DS usually involve mice which have been genetically altered to so that either this channel is mutated or deleted. But differences between the brains of humans and mice means that mice are not necessarily the best model for this rare disease. In this research, a team from Japan developed (iPSCs) from skin cells taken from an adult with DS who had a mutation in SCN1A. These cells were then differentiated into neurons allowing researchers to look at the effect of DS directly in human cells. Explaining their results Shinichi Hirose, PhD, from Fukuoka University (Fukuoka, Japan) said, “From research with mice we believed that SCN1A mutations affect GABAergic neurons in the forebrain from signalling properly. From the human neurons we also found that GABAergic neurons were affected by DS, especially during intense stimulation. These patient-derived cells provide an unparalleled insight into the mechanism behind DS and a unique platform for drug development.”

— Compiled by Robert Kimball, MDD Staff Writer robert.kimball@ahcmedia.com To subscribe, please call MEDICAL DEVICE DAILY™ Customer Service at (800) 477-6307; outside the U.S. and Canada, call (404) 262-5476. Copyright © 2013 AHC Media. Reproduction is strictly prohibited. Visit our web site at www.medicaldevicedaily.com.


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