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Friday, October 30, 2009

Pharmaxis applies to market Bronchitol™ for cystic fibrosis in Europe

Pharmaxis applies to market Bronchitol™ for cystic fibrosis in Europe Print E-mail
29 Oct 2009

Pharmaxis announced that it has filed an application with the European Medicines Agency (EMeA) to market Bronchitol in Europe for the treatment of cystic fibrosis

Sydney, Australia | October 29, 2009 | Pharmaceutical company Pharmaxis (ASX:PXS) today announced that it has filed an application with the European Medicines Agency (EMeA) to market Bronchitol in Europe for the treatment of cystic fibrosis.

Dr Alan Robertson, Pharmaxis Chief Executive Officer said; “We are excited to have arrived at this important milestone in bringing Bronchitol to the worldwide cystic fibrosis community. Since reporting positive results from our first Phase 3 trial in May of this year, a dedicated team within Pharmaxis has compiled the comprehensive electronic submission required and I am pleased to say it has been filed overnight with the EMeA.”

“Our marketing authorization application is being reviewed through the European Union’s centralized procedure and will, if successful, give us immediate access to all European Union member countries. There are approximately 40,000 people in Europe who are affected by cystic fibrosis. Pharmaxis expects to know the outcome of the review in the second half of 2010.”

In September Pharmaxis completed recruitment of a second Phase 3 clinical trial required for submission of a new drug application to the US Food and Drug Administration. The study is expected to report during the first half of 2010.

About Bronchitol

Pharmaxis Ltd is developing Bronchitol for the management of chronic obstructive lung diseases including bronchiectasis, cystic fibrosis and chronic bronchitis. Bronchitol is a proprietary formulation of mannitol administered as a dry powder in a convenient hand-held inhaler. It is designed to hydrate the lungs, restore normal lung clearance mechanisms, and help patients clear mucus more effectively. Clinical studies have shown Bronchitol to be well tolerated, to improve lung function and quality of life, and to stimulate mucus hydration and clearance in people with bronchiectasis and cystic fibrosis.

About Pharmaxis

Pharmaxis (ACN 082 811 630) is a specialist pharmaceutical company involved in the research, development and commercialization of therapeutic products for chronic respiratory and immune disorders. Its development pipeline of products includes Aridol for the management of asthma, Bronchitol for cystic fibrosis, bronchiectasis and chronic obstructive pulmonary disease (COPD), PXS25 for the treatment of lung fibrosis and PXS4159 for asthma.

Founded in 1998, Pharmaxis is listed on the Australian Securities Exchange (symbol PXS). The company is headquartered in Sydney at its TGA-approved manufacturing facilities. For more information about Pharmaxis, go to www.pharmaxis.com.au or contact Investor Relations on phone +61 2 9454 7200.

SOURCE: Pharmaxis Ltd,

DiscoveryBioMed Awarded $300,000 NIH Grant for Cystic Fibrosis Drug Research and Development

DiscoveryBioMed Awarded $300,000 NIH Grant for Cystic Fibrosis Drug Research and Development

Wed Oct 28, 2009 11:23am EDT
Phase 1 Small Business Innovation Research (SBIR) Grant to Fund Research Performed by On-Going Collaboration between DiscoveryBioMed and The Gregory Fleming James Cystic Fibrosis Research Center at the University of Alabama at Birmingham (UAB)

BIRMINGHAM, Ala.--(Business Wire)-- DiscoveryBioMed, Inc. (DBM) today announced that it has been awarded a Phase 1 Small Business Innovation Research (SBIR) grant by the National Institutes of Health (NIH). The $308,000 grant will be used to advance certain small molecule drug discovery programs designed to correct the genetic mutation most common to cystic fibrosis (CF).

"SBIR funding is an essential part of DiscoveryBioMed`s ability to provide our academic clients with cost-effective access to our world-class drug discovery engine," said Dr. Erik Schwiebert, Chief Executive Officer of DiscoveryBioMed. "By screening our test drugs on DBM`s proprietary disease-relevant human cell backgrounds, our clients are able to facilitate their basic research, bringing new therapies closer to patients.

The SBIR grant announced today is an example of this strategy in action." Dr. Schwiebert continued, "We are particularly pleased that the NIH has chosen to provide funding for this important drug discovery program and we are proud to be partnered with UAB`s Gregory Fleming James Cystic Fibrosis Research Center in the pursuit of new clinical treatments for Cystic Fibrosis."

To date, DiscoveryBioMed, along with partners, James Collawn, Ph.D. and Zsuzsa Bebok, M.D., have screened approximately 25,000 compounds as part of this program. As a result of the SBIR award announced today, the team will be able to screen 50,000-70,000 additional compounds. In addition, the collaboration has already yielded the discovery and validation of a panel of 5 lead corrector compounds with nanomolar potency and 10-20 fold greater potency that any existing corrector drugs.

Medicinal chemistry derivatives are currently being synthesized from the most potent lead compound from a family of drugs that had common molecular structure. Patent protection is in its final stages with work being facilitated by the UAB Research Foundation. DBM and UAB investigators have mutual rights to existing and future lead compounds going forward and have contributed equally to the partnership.

"We are extremely pleased to be working with DiscoveryBioMed. Their exceptional technology and excellent small molecule screening library make them an ideal partner for this program, said James F. Collawn, Ph.D., Professor of Cell Biology at UAB. "We look forward to a continued and active scientific collaboration with DiscoveryBioMed." Dr. Collawn continued, "The SBIR grant announced today is a meaningful endorsement of our efforts investigating novel approaches to the development of therapies for the treatment of patients with CF. We believe the human airway epithelial cell model, which was acquired and licensed by DiscoveryBioMed, expressing the mutant CFTR from an endogenous gene is currently the best model for studies of this type. The funds made available through the SBIR grant will allow us to explore new ideas regarding mutant CFTR rescue and may lead to treatment alternatives for CF patients in the near future."

The grant announced today is the second to be awarded to DBM this year. The previous award, announced in September, was a Phase 2 SBIR grant to continue research into the discovery and development of small molecules to alleviate multiple chronic human diseases. About DiscoveryBioMed, Inc. DiscoveryBioMed, Inc. is a life sciences and biotechnology company that engages in R&D and services work in cell engineering and production and cell-based drug discovery. T

he company is located within Innovation Depot in Birmingham. Using physiologically relevant cell culture models preferably derived from normal and diseased adult human cells and tissues, it focuses on finding therapeutic compounds for a variety of human diseases. It also applies this custom human cell-based approach to its "fee-for-service" support to researchers in allied areas and currently serves clients both locally in Alabama as well as in 11 other states in the US currently. For more information, visit the DBM website at www.discoverybiomed.com. Discovery BioMed, Inc. Erik Schwiebert, Ph.D., 205-307-6535 x 1 erik@discoverybiomed.com or Red Mountain Communications Jonathan M. Nugent, 205-566-3026 jnugent@redmtncom.com Copyright Business Wire 2009

Copyright Business Wire 2009

New Lung Tx Technology

Patients Waiting for Lung Transplants May Soon Breathe a Sigh of Relief

lung-transplantEmphysema and cystic fibrosis patients who need new lungs are faced with a life-threatening problem: more than 80 percent of donated lungs can’t be used—they’re inflamed and barely functional [Scientific American]. Transplanted lungs also fail at a much higher rate than other transplanted organs, as they’re more likely to be rejected by the recipient’s body. But a new procedure that makes use of gene therapy may soon double or triple the supply of undamaged donated lungs, and may also improve their function once transplanted.

In both pre- and post-transplant lungs, the problem is inflammation caused by insufficient amounts of an immune molecule called IL-10. Donated lungs are immediately chilled on ice, which destroys any IL-10 that may remain in the lungs, allowing substantial damage to occur before the organ can be implanted. And a lack of the molecule after transplantation increases the likelihood that inflammation will damage the organ and induce rejection [Los Angeles Times].

To get around these problems, the researchers first built a domed chamber where pig lungs were kept at body temperature with a steady flow of oxygen and nutrients moving through them. That arrangement alone prevented substantial damage to the lungs. Next, in the gene therapy stage, the researchers used a harmless virus to bring a gene that produces IL-10 into the lung cells.

Lead researcher Shaf Keshavjee explains that the lungs that received the therapy had better blood flow and were more able to take in oxygen and expel carbon dioxide, the study showed. “It’s as if gene therapy turbocharges each individual cell to manufacture many more proteins in its own IL-10 factory,” Keshavjee said [Bloomberg]. The lungs also performed better and were better tolerated by the pigs who received the transplants, according to the study published in Science Translational Medicine.

The researchers also tried the first parts of the procedure on donated human lungs that were too damaged to transplant. The human lungs showed the same improvements in blood flow and respiration, suggesting that the therapy could repair lungs that would otherwise have been discarded, and could therefore increase the stock of available organs. Last year, 234 people in the U.S. died while waiting for a lung transplant…. Currently, more than 1,800 people in the U.S. are waiting for a lung [Bloomberg].

The human lungs weren’t transplanted into sick patients, but if Keshavjee’s experiments continue to go well human trials could begin in about a year. While questions about gene therapy remain–in some cases, the viral vectors used to transport genes have been found to cause serious side effects–the new approach has the potential to be a breath of fresh air.


Thursday, October 29, 2009

Ten Steps to Preventing Infection in Hospitals

As CFer's, this is a no-brainer. We know that there is often poor infection control in the hospital setting.

But we're particularly vulnerable to picking up C Dif, MRSA and even Cepacia in hospitals if proper infection control isn't followed. I thought this article served as a great reminder for us all....

OCTOBER 27, 2009

Ten Steps to Preventing Infection in Hospitals
Too many patients get sick in the very places that are supposed to heal them


The facts are frightening: As many as one in 10 patients hospitalized in the U.S. will come down with an infection—often due to the very care that is supposed to be restoring health.
These infections afflict nearly two million patients a year, cause close to 100,000 deaths and cost up to $6.5 billion.

But they are not inevitable.

Here are 10 ways to prevent infection in health-care settings—a list gleaned from conversations with doctors, nurses, administrators, the nonprofit Committee to Reduce Infection Deaths, and the Association for Professionals in Infection Control and Epidemiology.
We've divided the list into two parts: first, promising new technologies, and second, a look at back-to-basics techniques that many hospitals have reinvigorated, with great success.

Some of the most vicious vectors of infection can survive for weeks on medical equipment and in patient rooms. The culprits include the drug-resistant MRSA bacteria, which can cause staph infections, and the nasty Clostridium difficile, or C. diff, which causes severe diarrhea.
Hospitals, of course, have rigorous protocols for cleaning. But how well are they doing?
To find out, Philip Carling, an epidemiologist at Caritas Carney Hospital in Dorchester, Mass., went undercover. He developed an invisible solution with fluorescent markers and sprayed it all over patient rooms in dozens of hospitals. Then he let cleaning crews do their thing. Afterward, he went over each room with a black light. Any spot the crews missed would glow fluorescent.
Turned out they missed a lot.

Toilets sparkled. But bathroom light switches and door knobs did not. Telephones, nurse-call buttons and grab rails were all routinely contaminated.

Showing the results to cleaning crews—and training them to do better—helped a great deal, boosting compliance with proper cleaning techniques to 77% from 44%. Dr. Carling has licensed the fluorescent solution and a training program to

2. ROBOTIC HELPERS When surgeon Bolanle Asiyanbola tested emergency-room equipment that had been disinfected by hand, she found one in four pieces was still contaminated with bacteria.
Enter SUDS, a shower-sized cubicle with a fogging mechanism inside.
Dr. Asiyanbola led the team at Johns Hopkins that developed SUDS to disinfect even the most hard-to-clean equipment, such as electrocardiogram wires. She recently published a study showing that devices cleaned in SUDS stayed clean for two days, even after they'd been reused.
SUDS is not yet on the market. But other systems are, among them the Bioquell Z, a little machine that sprays a disinfecting hydrogen-peroxide vapor—and looks an awful lot like the Star Wars robot R2D2.

Crews wheel the Bioquell Z, which is made by Bioquell Inc., of Horsham, Pa., into a patient's room and seal the door. About 90 minutes later, the room and any equipment inside are disinfected, with no residual smell.

3. COMPUTER SURVEILLANCE One of the hottest new fields in infection prevention is data mining. Software such as CareFusion Corp.'s MedMined Data Surveillance tracks a hospital's admission, discharge and transfer data and laboratory results.
The system might pick up on, say, a spike in urinary-tract infections on one floor. Doctors can then take immediate precautions—reviewing procedures, disinfecting equipment and checking for defective catheters.

Such software can cost tens of thousands of dollars to install and more to run, but devotees say it saves money and lives.

And don't underestimate the motivational power of data. Stephen Streed, director of epidemiology at Lee Memorial Health System in Florida, tracks infection rate by surgeon—and then posts a list annually in his four hospitals. The list is coded to protect anonymity, but each surgeon knows his or her ranking.

"They growl a bit, but then they find their way to my office and ask, 'Why am I in the bottom third of this list?' " Dr. Streed says. Those at the bottom soon improve. "It's a very, very powerful tool," he says.

4. BUG-BLASTING BATHS Recent research suggests that washing ill patients daily with a mild antibacterial soap can cut bloodstream infections dramatically.

The soap of choice, chlorhexidine glutonate, comes in several formulations, including a bar of soap and a baby-wipe cloth. It's available over the counter.

Many doctors are wary about prescribing antibacterial agents because overuse can spur the rapid evolution of drug-resistant bugs. But some experts suggest it may be helpful for patients facing surgery to shower with chlorhexidine for two to four days before the operation.

5. REPORTING LAWS At least 25 states have passed laws requiring hospitals to report rates of common infections. In most cases, the reports are—or soon will be—publicly available. That, of course, is a big incentive for hospitals to improve. Another incentive: Medicare now limits reimbursement for treatment of hospital-associated infections.

All this is helping change hospital culture. "We used to think of this as the job of the infection-control nurse," says Nancy Foster, a vice president at the American Hospital Association. "Now we know everyone needs to be involved."


1. HAND HYGIENE David Hooper, the chief of infection control at Massachusetts General Hospital, says the key to preventing infection is simple: Listen to your mother. "Wash your hands and clean your room," he says.

Hospitals that have placed dispensers of alcohol-based hand sanitizer at every turn—in patient rooms, in hallways, by elevators, at nursing stations—see a dramatic increase in compliance with basic hand hygiene, from less than 50% to 80% or more. That's a huge step toward preventing infection. [edited to add by Amy: these hand sanitizers do NOT kill C Diff and often don't work effectively against MRSA.... so WASH YOUR HANDS instead of using these hand sanitizers and demand that health care workers do the same]

2. CHECK-IT-TWICE LISTS Several years ago, Peter Pronovost, a critical-care specialist at Johns Hopkins Medical Center, began touting the humble checklist as a powerful tool to ensure procedures are done accurately and safely. (See the accompanying interview with Dr. Pronovost.)

Checklists are now common in intensive-care units and operating rooms—but they're also starting to pop up in bedside medical charts.

Some hospitals require each shift nurse to review a checklist for each patient, answering questions such as: Does this patient have a catheter? If so, is it still necessary?
"Patients get all these tubes stuck in them and they stay there forever because people forget about them," says Barbara DeBaun, a nurse who advises the Bay Area Patient Safety Collaborative in San Francisco. "That can be a major source of infection."

3. CAN'T-MISS KITS Hospitals have begun to create portable kits filled with all the equipment needed for common procedures, such as inserting an intraveneous line or changing a dressing. That way, the nurse doesn't have to run back to the supply closet mid-procedure because he's forgotten a sterile drape or a skin-prep solution. And he's less likely to forget those steps in the first place.

4. ORAL FIXATION Nurses can go a long way to preventing ventilator-associated pneumonia—one of the most common infections in intensive-care units—by regularly cleaning a patient's mouth, gums and teeth. This keeps bacteria to a minimum.

Elevating the head of the patient's bed at 30 to 35 degrees is also crucial. And patients should be weaned from sedation at regular intervals.

5. SWAB AND STUDY Quick diagnostic tests now allow hospitals to identify infected patients within hours, rather than days.

There's still debate about whether all incoming patients should be tested for particularly nasty pathogens such as MRSA.

But at the very least, when patients who do show symptoms are tested, the quick results can shape an effective response. The pathogen C. diff, for instance, is not killed by alcohol-based scrubs, so health-care providers and visitors must wash with soap and water upon entering and exiting rooms of infected patients.

Pulmozyme+Cipro in 1 dry powder = rad

Pharm Res. 2009 Oct 22. [Epub ahead of print]

Inhalable Antibiotic Delivery Using a Dry Powder Co-delivering Recombinant Deoxyribonuclease and Ciprofloxacin for Treatment of Cystic Fibrosis.

Yang Y, Tsifansky MD, Wu CJ, Yang HI, Schmidt G, Yeo Y.

School of Pharmacy and Pharmaceutical Sciences, Purdue University, 575 Stadium Mall Drive, West Lafayette, Indiana, 47907, USA.

PURPOSE: To achieve efficient antibiotic delivery to the cystic fibrosis (CF) airway using a single inhalable powder co-encapsulating a mucolytic and an antibiotic. METHODS: Inhalable dry powders containing deoxyribonuclease and/or ciprofloxacin (DNase, Cipro, and DNase/Cipro powders) were produced by spray-drying with dipalmitylphosphatidylcholine, albumin, and lactose as excipients, and their antibacterial effects were evaluated using the artificial sputum model.

RESULTS: All powders showed mass median aerodynamic diameters below 5 microm. Both drugs were loaded in the dry powders without loss in quantity and activity. Dry powders containing DNase significantly decreased the storage modulus of the artificial sputum medium in less than 30 min. When applied to artificial sputum laden with Pseudomonas aeruginosa, Cipro/DNase powder showed better antibacterial activity than Cipro powder. The higher activity of the Cipro/DNase powder is attributable to the mucolytic activity of DNase, which promotes penetration of the dry powder into the artificial sputum and efficient dissolution and diffusion of ciprofloxacin.

CONCLUSIONS: Inhalational delivery of antibiotics to the CF airway can be optimized when the sputum barrier is concomitantly addressed. Co-delivery of antibiotics and DNase using an inhalable particle system may be a promising strategy for local antipseudomonal therapy in the CF airway.

PMID: 19847626 [PubMed - as supplied by publisher]

Rescue of CF airway epithelial cell function in vitro by a CFTR potentiator, VX-770.

Proc Natl Acad Sci U S A. 2009 Oct 21. (hot off the press)

Rescue of CF airway epithelial cell function in vitro by a CFTR potentiator, VX-770.

Van Goor F, Hadida S, Grootenhuis PD, Burton B, Cao D, Neuberger T, Turnbull A, Singh A, Joubran J, Hazlewood A, Zhou J, McCartney J, Arumugam V, Decker C, Yang J, Young C, Olson ER, Wine JJ, Frizzell RA, Ashlock M, Negulescu P.

Vertex Pharmaceuticals Incorporated, 11010 Torreyana Road, San Diego, CA 92121.

Cystic fibrosis (CF) is a fatal genetic disease caused by mutations in the gene encoding the CF transmembrane conductance regulator (CFTR), a protein kinase A (PKA)-activated epithelial anion channel involved in salt and fluid transport in multiple organs, including the lung. Most CF mutations either reduce the number of CFTR channels at the cell surface (e.g., synthesis or processing mutations) or impair channel function (e.g., gating or conductance mutations) or both.

There are currently no approved therapies that target CFTR. Here we describe the in vitro pharmacology of VX-770, an orally bioavailable CFTR potentiator in clinical development for the treatment of CF. In recombinant cells VX-770 increased CFTR channel open probability (P(o)) in both the F508del processing mutation and the G551D gating mutation.

VX-770 also increased Cl(-) secretion in cultured human CF bronchial epithelia (HBE) carrying the G551D gating mutation on one allele and the F508del processing mutation on the other allele by approximately 10-fold, to approximately 50% of that observed in HBE isolated from individuals without CF.

Furthermore, VX-770 reduced excessive Na(+) and fluid absorption to prevent dehydration of the apical surface and increased cilia beating in these epithelial cultures. These results support the hypothesis that pharmacological agents that restore or increase CFTR function can rescue epithelial cell function in human CF airway.

New Clinical Guidelines For Exacerbations In Cystic Fibrosis

New Clinical Guidelines For Exacerbations In Cystic Fibrosis

24 Oct 2009

The American Thoracic Society has released new clinical guidelines for the treatment of exacerbations in cystic fibrosis based on a review of the literature on current clinical practices.

"This is the first such comprehensive and evidence-based systematic review of best practices for pulmonary exacerbation of cystic fibrosis," said Susanna McColley, M.D., head of the division of pulmonary medicine and director of the Cystic Fibrosis Center at Children's Memorial Hospital and associate professor at Northwestern University's Feinberg School of Medicine. "Until these, guidelines were arrived at by a less rigorous process based on the consensus of a committee of experts."

When cystic fibrosis patients suffer an acute exacerbation, they undergo an acute worsening of symptoms, which typically require medical intervention. While a prospective definition of an exacerbation has not yet been developed, clinical features are generally well-defined and represent a sharp deterioration in the general condition of the patient, often involving systemic symptoms such as weight loss and lack of appetite, as well as worsening of pulmonary symptoms such as cough, sputum production and shortness of breath. Exacerbations are the most common reason for hospitalization of cystic fibrosis patients.

The guidelines, which were presented at the North American Cystic Fibrosis Conference in October, highlighted a number of common practices in cystic fibrosis exacerbations.

The committee gave guidance on two areas of significant interest to clinicians: synergy testing and the dosing of aminoglycoside antibiotics. In the case of synergy testing - a costly and time-consuming practice of determining what synergistic effects different antibiotics may have when used together against multi-drug resistant infections - was found to have little benefit to the patient and the committee recommended against the routine use of it. In the case of aminoglycoside antibiotics, they found that three-times-daily dosing was no more effective than once-daily dosing and recommended once-daily dosing in most cases.

The committee also affirmatively recommended continuation of two current practices - continuing chronic therapies during exacerbation treatment and airway clearance therapies - both of which were found to have moderate benefits to the patient.

Perhaps most strikingly, the committee found that in six of ten investigated practices, there was simply not enough data to recommend for or against them. "This highlights that there are a lot of unanswered questions," said Dr. McColley, citing the need for research that would clarify whether there are different outcomes associated with the practices, which included inpatient versus outpatient care; simultaneous use of intravenous and inhaled antibiotics; number of antibiotics used to treat Pseudomonas aeruginosa; continuous infusion of betalactam antibiotics; and duration of antibiotic treatment.

"We have incomplete information, but the guidelines provide important guidance to physicians, patients, third party payers on the treatment of this serious and common complication of CF respiratory disease," she said. "By reducing variability in practice, implementation of these guidelines may help to improve outcomes of care."

Keely Savoie
American Thoracic Society

Article URL: http://www.medicalnewstoday.com/articles/168498.php

Now Recruiting: A New Gilead Medicine

A Randomized, Double-Blind, Placebo-Controlled Multiple Dose Trial of GS-9411 in Healthy Volunteers
This study is currently recruiting participants.
Verified by Gilead Sciences, October 2009
First Received: October 20, 2009 Last Updated: October 21, 2009 History of Changes
Sponsor: Gilead Sciences
Information provided by: Gilead Sciences
ClinicalTrials.gov Identifier: NCT00999531

The purpose of this study is to evaluate the safety and tolerability of repeated doses of GS-9411 in healthy volunteers. GS-9411 is a sodium channel inhibitor, that may restore airway hydration and mucociliary clearance in the lung.

Condition Intervention Phase
Cystic Fibrosis
Mucociliary Clearance
Airway Hydration
Drug: GS-9411
Drug: Placebo
Phase I

Study Type: Interventional
Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Safety Study
Official Title: A Phase 1, Randomized, Double-Blind, Placebo-Controlled Multiple Dose Trial to Assess the Safety, Tolerability, and Pharmacokinetics of GS-9411 in Healthy Volunteers

Resource links provided by NLM:

Further study details as provided by Gilead Sciences:

Primary Outcome Measures:
  • Safety and tolerability of multiple doses of inhaled GS-9411 in healthy volunteers [ Time Frame: 21 Days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Assess the pharmacokinetics of GS-9411 and its metabolites [ Time Frame: 21 Days ] [ Designated as safety issue: No ]

Estimated Enrollment: 24
Study Start Date: October 2009
Estimated Study Completion Date: December 2009
Estimated Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
1: Experimental
GS-9411 9.6 mg
Drug: GS-9411
Inhaled GS-9411 dissolved in sterile saline
2: Experimental
GS-9411 4.8 mg
Drug: GS-9411
Inhaled GS-9411 dissolved in sterile saline
3: Placebo Comparator
Placebo, sterile saline
Drug: Placebo
Inhaled Placebo, sterile saline

Detailed Description:

GS-9411 is being evaluated as a potential therapy to improve airway hydration and mucociliary clearance in patients with cystic fibrosis. This study is evaluating the safety and tolerability of 2 dose levels of GS-9411 as an inhaled product, compared to a matched placebo, administered twice daily for 14 days.


Ages Eligible for Study: 18 Years to 65 Years
Genders Eligible for Study: Both
Accepts Healthy Volunteers: Yes

Inclusion Criteria:

  • Males and females, 18 to 65 years of age
  • No clinically important abnormal physical findings at Screening
  • No clinically relevant abnormalities in the results of laboratory evaluation at Screening
  • Must test negative for hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV) at Screening
  • Normal electrocardiogram (ECG) at Screening
  • Normal blood pressure (BP) and heart rate (HR) in the absence of any medications for
  • Body weight between 50 and 100 kg and within ± 15% of ideal body weight or body mass index (BMI) between 18 and 28 kg/m2 at Screening
  • Able to communicate well with the investigator and to comply with the requirements of the entire study
  • Provision of written informed consent to participate as shown by a signature on the volunteer consent form
  • Nonsmokers of at least 180 days (6 months) duration (<>
  • Negative for drugs of abuse (including alcohol) at Screening and Day -5
  • Must be willing to abstain from alcohol and strenuous exercise during the 48 hours prior to Day -5 and during the study
  • Forced expiratory volume in 1 second (FEV1) ≥ 80% of predicted normal for age, gender, and height at Screening and predose
  • Normal intraocular pressure (IOP) between 10 and 21 mm Hg at Screening
  • Male subjects who are sexually active must be willing to use effective barrier contraception (e.g., condoms) during heterosexual intercourse from Day -5 through completion of the study and continuing for at least 90 days from date of last dose of study drug
  • Male subjects must refrain from sperm donation from Day -5 through completion of the study and continuing for at least 90 days from the date of last dose of study drug
  • Non-lactating females. Females on hormone replacement therapy (estrogen/progesterone) or contraceptive therapy must be stabilized on a product and dose for at least 90 days prior to Screening
  • Females must have a negative serum gonadotropin pregnancy test at Screening and Day -1
  • Nonpregnant females of childbearing potential must agree to use highly effective (<1%>

Exclusion Criteria:

  • Any prior exposure to GS-9411
  • Administration of any investigational drug in the period 84 days (12 weeks) prior to Screening; 112 days (16 weeks) if the previous investigational drug was a new chemical entity
  • A need for any medication during the period 0 to 5 days prior to Screening, except those deemed by the principal investigator/clinical investigator not to interfere with the outcome of the study
  • Existence of any surgical or medical condition which, in the judgment of the clinical investigator, might interfere with the absorption, distribution, metabolism, or excretion of the drug
  • Presence or history of allergy requiring treatment. Hay fever is allowed unless it is active or has required treatment within 56 days (8 weeks) of Screening
  • Donation or loss of greater than 400 mL of blood in the period 84 days (12 weeks) prior to Screening
  • Serious adverse reaction or hypersensitivity to any drug
  • Presence or history of any pulmonary diseases (e.g., asthma, emphysema, chronic bronchitis, CF, bronchiectasis)
  • Consumption of drugs and/or herbal preparations capable of inducing hepatic enzyme metabolism (e.g., barbiturates, rifampicin, carbamazepine, phenytoin, primidone, or St. John's Wort) or enzyme-inhibiting agents (e.g., cimetidine) or similar drugs within 28 days (or 5 half-lives of inducing/inhibiting agent, whichever is longer) of Screening
  • Major surgery within 180 days (6 months) of the start of this study
  • Subjects who have experienced a significant upper or lower respiratory tract infection within the 42 days (6 weeks) prior to Screening
  • Subjects with significant history of respiratory, renal, hepatic, cardiovascular (including history of systemic hypertension requiring therapy), metabolic, neurological, hematological, gastrointestinal, cerebrovascular, or other significant medical illness or disorder which, in the judgment of the investigator, may interfere with the study or require treatment which may affect the evaluation of the safety of the study drug
  • Subjects with elevated liver enzyme concentrations at Screening and at Day -1
  • Hemoglobin level <>
  • Serum potassium > 5 mEq/L taken at Screening and at Day -1
  • Poor venous access
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00999531

Contact: Bianca Scott 613-9076-9825 b.scott@nucleusnetwork.com.au

Australia, Victoria
Nucleus Network, Ltd. Recruiting
Melbourne, Victoria, Australia
Principal Investigator: Peter Hodsman, MD
Sponsors and Collaborators
Gilead Sciences
Principal Investigator: Peter Hodsman, MD Nucleus Network Ltd
More Information
No publications provided

Responsible Party: Gilead Sciences, Inc. ( Thomas O'Riordan, MD )
Study ID Numbers: GS-US-221-0107
Study First Received: October 20, 2009
Last Updated: October 21, 2009
ClinicalTrials.gov Identifier: NCT00999531 History of Changes
Health Authority: Australia: Department of Health and Ageing Therapeutic Goods Administration

Keywords provided by Gilead Sciences:
Cystic Fibrosis
Mucociliary Clearance
Epithelial Sodium Channel Inhibitor
ENaC Inhibitor
Airway Hydration

Additional relevant MeSH terms:
Pathologic Processes
Digestive System Diseases
Genetic Diseases, Inborn
Respiratory Tract Diseases
Lung Diseases
Infant, Newborn, Diseases
Pancreatic Diseases
Cystic Fibrosis

ClinicalTrials.gov processed this record on October 27, 2009


Does Levitra Normalize the Nasal Potential Difference in Cystic Fibrosis Patients?

Does a Nasal Instillation of Vardenafil Normalize the Nasal Potential Difference in Cystic Fibrosis Patients?
This study is not yet open for participant recruitment.
Verified by Cliniques universitaires Saint-Luc- Université Catholique de Louvain, October 2009
First Received: October 26, 2009 No Changes Posted
Sponsored by: Cliniques universitaires Saint-Luc- Université Catholique de Louvain
Information provided by: Cliniques universitaires Saint-Luc- Université Catholique de Louvain
ClinicalTrials.gov Identifier: NCT01002534

The purpose of this study is to investigate the effect of a nasal instillation of Vardenafil on nasal potential difference in cystic fibrosis patients homozygous for the F508del mutation

Condition Intervention Phase
Cystic Fibrosis
Drug: Vardenafil
Drug: Placebo
Phase II

Study Type: Interventional
Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator), Placebo Control, Crossover Assignment, Efficacy Study
Official Title: Does a Nasal Instillation of Vardenafil Normalize the Nasal Potential Difference in Cystic Fibrosis Patients Homozygous for the F508del Mutation? A Randomized, Double Blind, Placebo-controlled Study.

Resource links provided by NLM:

Further study details as provided by Cliniques universitaires Saint-Luc- Université Catholique de Louvain:

Primary Outcome Measures:
  • Cumulated changes in response to Chloride-free solution and isoproterenol (reflecting chloride transport) [ Time Frame: Change from baseline (visit 1) and placebo to Vardenafil instillation ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change in basal voltage value and in amiloride response (reflecting sodium transport) [ Time Frame: Change from baseline (visit1) and placebo to Vardenafil instillation ] [ Designated as safety issue: No ]

Estimated Enrollment: 10
Study Start Date: December 2009
Estimated Study Completion Date: March 2010
Estimated Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
baseline: No Intervention
visit 1

Vardenafil: Active Comparator
nasal instillation of Vardenafil ( visit 2 or 3)
Drug: Vardenafil
Nasal instillation of Vardenafil
Placebo: Placebo Comparator
Nasal instillation of placebo (visit 3 or 2)
Drug: Placebo
Nasal instillation of placebo matching in appearance with the Vardenafil instillation

Detailed Description:

CFTR protein has been shown to be an ohmic, small conductance channel regulated by cAMP intracellular levels that are balanced by degradation through cyclic nucleotide phosphodiesterases (PDE). Several families of PDEs with varying selectivities for cAMP and/or cGMP have been identified. PDE5 is highly specific for cGMP and is involved in the regulation of the intracellular concentration of cGMP in various tissues. Recently, it has been shown , in a preclinical model of transgenic mice , that pharmacological doses of sildenafil and vardenafil, two clinically approved PDE5 inhibitors, stimulate chloride transport activity of the mutant F508del-protein (Lubamba et al, 2008); this parameter has been assessed by means of the nasal potential difference (NPD).An increasing effect od sildenafil on the expression of F508del-CFTR protein (Dormer et al, 2005) was originally reported in nasal epithelial cells harvested from patients with cystic fibrosis and cultured on impermeable supports, a configuration that allows interaction of drugs with the apical side of epithelia.

This study aims to investigate the effect of a single local administration of vardenafil on NPD measurements in CF patients homozygous for the F508del mutation.


Ages Eligible for Study: 14 Years and older
Genders Eligible for Study: Both
Accepts Healthy Volunteers: No

Inclusion Criteria:

  • Cystic fibrosis patients homozygous for the F508del mutation as confirmed by a genetic test
  • Aged 14 years and older
  • Male and female
  • FEV1 >50% of predicted normal

Exclusion Criteria:

  • Acute respiratory tract infection or pulmonary exacerbation requiring antibiotic intervention within 2 weeks of visit 1
  • Any condition prohibiting the correct measurement of the NPD
  • Active or passive smoking
  • Planned treatment or treatment with another investigational drug or therapy within 1 month prior to randomisation
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01002534

Contact: Patrick LEBECQUE, MD, PhD +32 2 764 1111 ext 1939 patrick.lebecque@uclouvain.be
Contact: Teresinha LEAL, MD, PhD +32 2 764 6724 teresinha.leal@uclouvain.be

Cliniques universitaires St. Luc
Brussels, Belgium, 1200
Sponsors and Collaborators
Cliniques universitaires Saint-Luc- Université Catholique de Louvain
Principal Investigator: Patrick LEBECQUE, MD, PhD Cliniques universitaires St.Luc (Université catholique de Louvain)
Principal Investigator: Teresinha LEAL, MD, PhD Cliniques universitaires St.Luc ( Université Catholique de Louvain)
More Information
Responsible Party: Cliniques universitaires Saint-Luc (Université Catholique de Louvain) ( Patrick Lebecque, MD, PhD )
Study ID Numbers: VARD-99
Study First Received: October 26, 2009
Last Updated: October 26, 2009
ClinicalTrials.gov Identifier: NCT01002534 History of Changes
Health Authority: Belgium: Federal Agency for Medicinal Products and Health Products

Keywords provided by Cliniques universitaires Saint-Luc- Université Catholique de Louvain:
Cystic Fibrosis
Nasal instillation
Nasal Potential difference

Additional relevant MeSH terms:
Cystic Fibrosis
Molecular Mechanisms of Pharmacological Action
Enzyme Inhibitors
Pharmacologic Actions
Digestive System Diseases
Pathologic Processes
Phosphodiesterase Inhibitors
Respiratory Tract Diseases
Genetic Diseases, Inborn
Lung Diseases
Pancreatic Diseases
Infant, Newborn, Diseases

ClinicalTrials.gov processed this record on October 27, 2009


Napo Acquires Rights to Additional CFTR Technology

Napo Acquires Rights to Additional CFTR Technology

Indications Include Gastrointestinal and Polycystic Kidney Disease

SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)--Napo Pharmaceuticals, Inc. has in-licensed from the University of California Regents additional small-molecule cystic fibrosis transmembrane conductance regulator (CFTR) inhibitor technology including gastrointestinal (GI) and polycystic kidney disease (PKD) indications. PKD, a leading cause of end-stage renal disease and kidney transplants, affects approximately 600,000 people in the United States, and 12.5 million worldwide, according to the PKD Foundation.

Napo’s collaborator, Alan Verkman, M.D., Ph.D., of the University of California San Francisco (UCSF) Department of Medicine, was recently awarded a National Institutes of Health (NIH) challenge grant to further evaluate CFTR inhibitor technology targeting PKD. The goal of the NIH funded study is to evaluate a select group of CFTR inhibitors that, when orally administered, are effective in preventing renal cyst growth and renal function deterioration in mice.

Napo has exclusive rights to several classes of novel, proprietary, small-molecule CFTR inhibitors, which it is developing for a variety of indications, including PKD and secretory diarrheas, which may include diarrheas of infectious or other origins. To advance candidate molecules for both indications, Napo intends to leverage the knowledge of secretory biology and clinical development it has gained from its work with crofelemer, the company’s lead molecule and first-in-class CFTR inhibitor. Crofelemer, which is extracted and purified from a rain forest plant and cannot be synthesized, is too large to be significantly absorbed, making it a locally acting anti-diarrheal agent.

Napo’s licensee, Salix Pharmaceuticals, Inc., is evaluating crofelemer as a treatment for chronic diarrhea in people living with HIV/AIDS on anti-retroviral therapy in a final Phase 3 study called the ADVENT trial. Another Napo licensee, Glenmark Pharmaceuticals, Ltd., is testing crofelemer for use in late-stage adult acute infectious diarrhea (AAID) in India, and plans to expand its studies to severe diarrheal infection (including cholera) and pediatric diarrhea.

Earlier this year, Napo announced that SRI International had begun an early-stage discovery/pre-clinical drug development program using small molecules from Napo’s portfolio of CFTR inhibitor candidates. Special funding for this program was provided by the National Institute of Allergy and Infectious Diseases’ Division of Microbiology and Infectious Diseases (DMID) at the NIH in response to the dire need for novel drugs for additional treatment options for secretory diarrhea and GI disorders. SRI’s activities are focused on refining leads for further pre-clinical studies supporting the filing of an Investigational New Drug (IND) application for a small-molecule CFTR inhibitor.

“This is the second time this year that the CFTR technology has been recognized through NIH funding as an important mechanism in treatment of diarrheal diseases and PKD,” said Napo CEO Lisa Conte. “Two to three million children die each year from secretory diarrhea, and there are no therapeutic options for PKD, leading to dialysis and transplant options only for the patients.”

About CFTR

The cystic fibrosis transmembrane conductance regulator (CFTR) is a cAMP-activated chloride ion (Cl-) channel expressed in various epithelial cells throughout the body, and is a pharmacological target for both activators and inhibitors. Activators are useful in the pharmacotherapy of cystic fibrosis. CFTR inhibitors, such as Napo’s compounds, play a role in modulating and reducing water flow across gut epithelium and kidney cysts through the regulation of the CFTR channel. The collaboration between Napo and UCSF identified a variety of potent inhibitors of CFTR activity.

About Crofelemer

Napo’s proprietary patented gastrointestinal compound, crofelemer, is a first-in-class anti-secretory agent extracted from Croton lechleri, a medicinal plant sustainably harvested in several South American countries. The FDA has granted fast-track status to the development of crofelemer for HIV-related indications. The compound is in various stages of clinical studies for the following four indications:

  • CRO-HIV for HIV-related diarrhea, ongoing Phase 3 (under Special Protocol Assessment)
  • CRO-IBS for diarrhea-predominant irritable bowel syndrome (D-IBS), Phase 2 completed
  • CRO-ID for acute infectious diarrhea (including cholera), Phase 2 completed
  • CRO-PED for pediatric diarrhea, Phase 1 completed; additional studies slated for the first half of 2011

Napo’s licensee, Salix Pharmaceuticals, Inc., has exclusive rights to crofelemer for all indications in North America, Europe (excluding Iceland, Liechtenstein, Norway, and Switzerland), and Japan, and, for certain other indications including irritable bowel syndrome, worldwide. Salix estimates that the HIV-associated diarrhea market opportunity alone may be $300 million. The ADVENT trial of crofelemer as a treatment for chronic diarrhea in patients on antiretroviral therapies for HIV or AIDS is being conducted under fast-track status and Special Protocol Assessment agreement with the FDA.

Crofelemer has also been licensed to Glenmark Pharmaceuticals, Ltd. in India and 140 emerging countries. Glenmark is planning development for multiple indications and populations including HIV (CRO-HIV), acute adult infectious diarrhea (CRO-ID), and pediatric diarrhea (CRO-PED). It anticipates approval of crofelemer in India in 2010. Luye Pharma Group, Ltd. (formerly Asiapharm Group, Ltd.) has rights to crofelemer in China, including Hong Kong and Macau.

About Napo Pharmaceuticals, Inc.

Napo Pharmaceuticals, Inc. focuses on the development and commercialization of proprietary pharmaceuticals for the global marketplace in collaboration with local partners. The company seeks partners in both traditional high-value markets and in the higher volume business models of emerging and developing economies. Napo was founded in November 2001 and is based in South San Francisco, Calif., with a subsidiary in Mumbai, India.

Napo’s pipeline includes crofelemer, which is in clinical development for 4 distinct indications, including a Phase 3 study; a small-molecule CFTR inhibitor program; and NP-500 for the treatment of Type II diabetes and metabolic syndrome, with Phase 1 studies completed. In addition, Napo has a library of approximately 2,300 medicinal plants collected from tropical areas through the company’s primary research on plants and the indigenous knowledge of their therapeutic uses.

Please note that the materials provided herein contain projections and other forward-looking statements regarding future events. Such statements are just predictions and are subject to risks and uncertainties that could cause the actual events or results to differ materially. These risks and uncertainties include, among others: the cost and unpredictability of the duration and results of clinical trials and FDA approval; the possible impairment of, or inability to obtain, intellectual property rights and the costs of obtaining such rights from third parties; market acceptance for approved products; ability to secure the product; and generic and other competition and the need to acquire new products.

Friday, October 23, 2009

1st dose of Denufosol (or placebo)

I'm in clinic right now, doing my 1st dose of either placebo or Denufosol.

I'm coughing quite a bit - my hunch is I'm not on placebo (even HTS doesn't make me cough this much).

But we'll see. More info to come later.....

Monday, October 19, 2009

KaloBios' KB001 Antibody Shows Encouraging Safety And Activity In New Approach To Fighting Pseudomonas Infection In Cystic Fibrosis Patients

KaloBios' KB001 Antibody Shows Encouraging Safety And Activity In New Approach To Fighting Pseudomonas Infection In Cystic Fibrosis Patients

Article Date: 18 Oct 2009 - 0:00 PDT

Phase 1/2 clinical trial results with KB001, a Humaneered™, high-affinity antibody fragment under development by KaloBios Pharmaceuticals, Inc. in cystic fibrosis patients showed an acceptable safety profile as well as trends toward reducing tissue inflammation and clearance of the bacterium. Results of the multi-center, randomized, double-blind, single-dose, placebo-controlled study are being presented today at the North American Cystic Fibrosis Conference in Minneapolis, MN. KaloBios is developing KB001 for the treatment and/or prevention of Pseudomonas aeruginosa infections in both cystic fibrosis patients and intensive care patients on ventilation, for whom Pseudomonas-caused pneumonia is a major costly health care problem.

"KB001 is designed to fight Pseudomonas aeruginosa (Pa) by blocking a virulence mechanism (the Type Three Secretion System or TTSS) on the bacterium's external surface that enables Pa to perforate and kill white blood cells and epithelial cells, and trigger tissue-damaging inflammation," said Dr. Geoff Yarranton, Kalobios' chief scientific officer. "By blocking Pa's killing mechanism, KB001 is intended to reduce the inflammation and exacerbations that are associated with the damage done to the lungs by Pa, and potentially enable the patient's own immune system to effectively fight and clear the bacterium from sites of infection. This contrasts with antibiotics like tobramycin that directly kill Pa, but quickly lose effectiveness if the bacteria become resistant to the drug."

The Phase 1/2 study enrolled two cohorts of approximately 12 patients who were randomized at a 2:1 ratio to receive a single IV infusion of KB001 or placebo at either 3.0 mg/kg or 10 mg/kg. Patients were followed for eight weeks. Results showed KB001 to be safe and non-immunogenic. An analysis of exploratory endpoints showed that there was an encouraging anti-inflammatory impact as measured by dose-related reductions in inflammatory markers, including neutrophils, IL-8, elastase, MPO, macrophages, and IL-1. There was also a trend in reducing mucoid and total Pa burden at day 56.

"We are very pleased with these initial clinical results for KB001, which we believe support conducting larger randomized clinical trials to further evaluate KB001's safety and clinical benefits for patients with cystic fibrosis," said Tillman Pearce, KaloBios' chief medical officer. "KB001 is a highly novel approach to treating Pseudomonas and now has shown promising data in both ventilator-associated pneumonia patients and cystic fibrosis patients."

Pseudomonas infection is a major unmet medical need with strains found all over the world that are resistant to common antibiotics. KaloBios is actively seeking a partner to help move this program forward and to ultimately capture the potential market of over $500 million that would exist for a safe and effective anti-Pseudomonas therapy.

For more information about KB001, please visit the KaloBios website.


Sunday, October 18, 2009

Desaturation during sleep can be predicted by FEV1 <64%

Desaturation during sleep can be predicted by FEV1 <64%

Nocturnal hypoxia and sleep disturbances in cystic fibrosis.

Universidade Federal do Ceara, Fortaleza, Ceará, Brazil.

Disrupted sleep and nocturnal hypoxia are common in cystic fibrosis (CF). However, the predictors of nocturnal hypoxia in CF are still controversial. In order to identify the risk factors for nocturnal desaturation and sleep disturbances, we carried out a clinical and polysomnographic investigation of CF patients.

We studied 30 clinically stable CF cases with clinical lung disease (mean age = 12.8; mean FEV1 = 65.2), 10 CF cases without significant lung disease (mean age = 13.3; mean FEV1 = 99.8), and 20 controls (mean age = 15.5). Patients were evaluated by spirometry, 6-min walk test, the Shwachman-Kulczycki (S-K) score, and full overnight polysomnography. Cases with clinical lung disease had lower body mass index, forced vital capacity, and S-K scores.

During sleep, five CF cases with clinical lung disease (15%) had SaO(2) <90% p =" 0.02)." sensitivity =" 92.3%;" specificity =" 77.3%)" sensitivity =" 81.8%;" specificity =" 85.2%).">

requency of impaired sleep was not different in CF cases with (N = 2) and without significant lung disease (N = 5, P = 0.53). Sleep architecture was not significantly different between the two groups. Sleep apnea was present in three CF cases with clinical lung disease and in one case without significant lung disease.

In summary, desaturation during sleep can be predicted by FEV1 <64%>. There are no significant differences in sleep architecture between clinically stable CF cases with and without significant lung disease. Pediatr Pulmonol. (c)2009 Wiley-Liss, Inc.

PMID: 19824056 [PubMed - as supplied by publisher]

Amniotic Fluid Digestive Enzyme Analysis Is Useful for Identifying CFTR Gene Mutations of Unclear Significance.

Amniotic Fluid Digestive Enzyme Analysis Is Useful for Identifying CFTR Gene Mutations of Unclear Significance.

Oca F, Dreux S, Gérard B, Simon-Bouy B, de Becdelièvre A, Ferec C, Girodon E, Muller F.

Biochimie-Hormonologie, Hôpital Robert Debré, AP-HP, Paris, France.

BACKGROUND: The large number of CFTR [cystic fibrosis transmembrane conductance regulator (ATP-binding cassette sub-family C, member 7)] mutations and the existence of variants of unclear significance complicate the prenatal diagnosis of cystic fibrosis (CF). The aim of this study was to determine whether the pattern of amniotic fluid digestive enzymes (AF-DEs) could be correlated with the severity of CFTR mutations.

METHODS: The AF-DE pattern (gamma-glutamyltranspeptidase, aminopeptidase M, and the intestinal isoform of alkaline phosphatase) was retrospectively analyzed in 43 AF samples. All fetuses presented 2 CFTR mutations, which were classified according to the severity of the disease: CF/CF (n = 38); CF/CFTR-related disorders (n = 1); and CF/unknown variant (n = 4). The relationships between clinical CF status, CFTR mutations, and AF-DE pattern were studied.

RESULTS: Of 38 severely affected CF fetuses, an "obstructive" AF-DE pattern was observed in 15 of 15 samples collected before 22 weeks, irrespective of the CFTR mutation (diagnostic sensitivity, 100%; diagnostic specificity, 99.8%). In the 23 fetuses evaluated after 22 weeks, the AF-DE pattern was abnormal in 7 cases and noncontributive in 16 (diagnostic sensitivity, 30.4%; diagnostic specificity, 99.8%). Of the 5 questionable cases (F508del/N1224K, F508del/L73F, 3849+10kbC>T/G1127E, F508del/S1235R, F508del/G622D), all were CF symptom free at 2-4 years of follow-up. The AF-DE pattern (<22 weeks) was typical in 3 cases but abnormal in the last 2 cases.

CONCLUSIONS: AF-DE analysis is of value for prenatal CF diagnosis in classic forms of CF and could be helpful in nonclassic CF.

PMID: 19833837 [PubMed - as supplied by publisher]