Primary Pulmonary Hypertension News - Menu TOPIGEN Introduces FANA(TM) Technology, New 3rd Generation Chemistry for Oligonucleotide-Based Therapeutics MONTREAL, and RANDOLPH, N.J., June 8 /PRNewswire/ -- TOPIGEN Pharmaceuticals Inc., a developer of multi-targeted respiratory products that inhibit pathways involved in cellular recruitment and inflammation, today introduced FANA(TM) Technology, a new generation of chemistry with potential for broad gene-targeting drug applications. "FANA (Fluoro Arabino Nucleic Acid) is unique among oligonucleotide chemistries. The platform uses an important modification in the sugar unit of the oligonucleotide chain that renders the FANA structure (arabinose sugar) much more stable than the normal ribose structure (RNA)," said Dr. Masad J. Damha, inventor of FANA and a James McGill Professor of Chemistry at McGill University. "This new chemistry platform significantly improves the functionality of oligonucleotides for gene targeting and silencing and offers an alternative to the traditional antisense and RNAi approaches," Dr. Damha added. In a series of studies comparing available gene modulating chemistries, FANA showed an improvement in target affinity and duration of gene response while improving efficacy and safety. FANA significantly enhances nuclease resistance, providing lower dosage requirements and the potential for improved systemic administration. "FANA represents a potentially important advance for nucleic acid-based therapeutics," said Alan M. Gewirtz, MD, Professor of Medicine at University of Pennsylvania, Division of Hematology/Oncology. This new chemistry has the potential to effectively address some previously identified shortcomings of older antisense-based drugs. The ability to achieve a specific, long-lasting knockdown of a targeted gene will represent a true advance in the field and hopefully stimulate renewed interest in the area of therapeutic oligonucleotides," Dr. Gewirtz added. The unique characteristics of FANA could be advantageous for a wide variety of therapeutic gene modifying applications, including topical and systemic administration. TOPIGEN is currently developing a novel, multi-targeted drug product for COPD utilizing FANA technology. Delivered via aerosol, the product (PD-3) is designed to inhibit gene expression pathways linked to the progressive airway remodeling associated with the disease. The drug candidate is scheduled to enter clinical trials in 2007. TOPIGEN has engaged Phoenix IP Ventures to be its exclusive representative in seeking development collaborations and licensing agreements for the technology outside of its core respiratory fields of interest. About TOPIGEN TOPIGEN's lead product for asthma, ASM8, is an inhaled, modified oligonucleotide currently undergoing human Phase 1 clinical studies. The Company believes that ASM8 has the potential to replace steroids in the treatment of asthma and may provide patients with a convenient once-a-day topical dosing regimen and an improved side-effect profile over other medications currently available. About Phoenix IP Ventures For licensing information on FANA(TM) Technology, please contact: Lisa Gray, Managing Partner, Phoenix IP Ventures, (267) 765-3233, or at lisa@phoenixipv.com. Editor's Note: Dr. Paul Wotton, President and Chief Executive Officer of TOPIGEN Pharmaceuticals will be presenting at the BIO 2005 Business Forum in Philadelphia, PA. The presentation will take place Monday, June 20, 2005 at 2:30 PM in Room B at the Pennsylvania Convention Center (1101 Arch Street). One-on-one meetings are available for attending media.
Public release date: 1-Jul-2005 American Thoracic Society Journal news tips for July 2005 (first issue) EXPOSURE TO PASSIVE SMOKE IN THE WOMB OR IN CHILDHOOD LINKED TO ASTHMA DEVELOPMENT Children's exposure to pre- and post-natal tobacco smoke carries a substantial risk for them to develop asthma and respiratory symptoms as adults, according to study results in the first issue for July 2005 of the American Thoracic Society's (ATS) peer-reviewed American Journal of Respiratory and Critical Care Medicine. Investigators conducted an 11-year community cohort study on the incidence of asthma and respiratory symptoms among a sample population in western Norway. The study included data from 2,819 respondents to both baseline and follow-up questionnaires. The researchers examined the incidence of asthma and five respiratory symptoms related to self-reported exposure from those surveyed to maternal smoking while in the womb and during childhood. The medical scientists also examined exposure to passive smoking from other household members during the individual's childhood. The researchers noted that the combined total exposure for the children to environmental tobacco smoke could explain almost one-quarter of the cases of adult asthma. They said that the estimated attributable fractions suggest that almost a quarter of the incidence cases of adult asthma could be prevented if children were not exposed to pre- and post-natal environmental tobacco smoke. They pointed out that they believed this was the first study to show that pre- and post-natal passive smoking induces a lasting vulnerability to asthma or respiratory symptoms. The survey was conducted in 1985 and 1996/97 on a random sample of the population of the city of Bergen and 11 surrounding municipalities in western Norway. The first questionnaire to be mailed out contained 40 questions about respiratory health, allergies, smoking habits, and occupational exposure. After two reminder letters, 3,370 subjects responded. A follow-up mailing 11 years later extended the questionnaire to 58 questions, adding queries on education and passive smoking. A total of 2,819 subjects returned the questionnaire in 1996 and 1997, after two written reminders and a phone call. In addition to their results on passive smoking, the investigators found no statistically significant relationship between the exposures in question and such confounders as the subject's sex, age, educational level, smoking habits, pack years, occupational exposure, and hay fever. DIFFERENT FACTORS ARE ASSOCIATED WITH ASTHMA DEVELOPMENT IN MALES AND FEMALES AT VARYING AGES A study of a large cohort of 1,022 children born in New Zealand who were followed from birth to age 26 revealed that there are different mechanisms associated with the development of asthma at varying ages between males and females. They found that factors predicting asthma and wheeze differed between the sexes and between childhood and adolescence. In their study, the authors revealed that males more often had childhood wheeze and that females were more likely to display adolescent-onset wheeze. The researchers pointed out that of the 1,022 study members included in their analysis, 474 were classified, by age 26, as "wheezers," as reported on two or more assessments. Of this group, slightly over 50 percent were male. But among the males who developed wheeze by age 26, 63 percent did so before age 10. According to data from the study, females who developed wheeze at any age up to 26 had a higher body mass index from age 9 forward. They were also more likely to have had a father with a history of atopy (inherited tendency to allergy), but were less likely to have owned a dog before age 9. Maternal atopy (either for asthma or hay fever) was a risk factor for childhood wheeze in both sexes. In addition, paternal atopy influenced childhood wheeze significantly for males. Smoking at age 15 was a risk factor for adolescent-onset wheeze for both males and females. All other risk factors for adolescent-onset wheeze differed between the sexes. The authors point out that several studies have suggested that female sex hormones influence factors associated with asthma. For example, atopy as measured by skin-prick allergen tests changes during the menstrual cycle. When estrogen levels are high, wheal and flare responses increase. Also, the reaction of peripheral white blood cells to the allergen pokeweed is increased in the presence of estrogen, while testosterone inhibits the response. The study appears in the first issue for July 2005 of the ATS peer-reviewed American Journal of Respiratory and Critical Care Medicine. PULMONARY REHABILITATION PROGRAMS FOR CHRONIC OBSTRUCTIVE PULMONARY DISEASE Incremental exercise tests show that the peak work rate in patients who suffer from chronic obstructive pulmonary disease (COPD) and who have participated in a pulmonary rehabilitation program increases an average of 18 percent, according to a "State of the Art" article on COPD pulmonary rehabilitation in the first issue for July 2005 of the American Thoracic Society's peer-reviewed American Journal of Respiratory and Critical Care Medicine. According to the expert article, the goals of pulmonary rehabilitation programs for COPD patients are to reduce symptoms, improve activity and daily function, and restore the highest level of independent function in patients with respiratory disease. COPD involves persistent obstruction of the airways caused by severe emphysema and chronic bronchitis. Severe emphysema causes enlargement of the tiny air sacs of the lung (alveoli) and the destruction of their walls. In chronic bronchitis, bronchial glands are enlarged, causing excess secretion of mucus. Frequently, the small airways of the lung become inflamed and blocked. Also, bronchitis victims suffer from a persistent cough that produces sputum. Long-term smoking is the root cause of each of the two illnesses involved. In 2002, 11.2 million U.S. adults were estimated to have COPD. One of the benefits of pulmonary rehabilitation is improved function capacity, as measured by the 6-minute walk test. Patients who underwent rehabilitation, including exercise training, improved their results by a distance of 54 meters (about 48.6 yards). Also, the authors point out that improved health-related quality of life is also observed even in the absence of clinically significant improvements in exercise capacity. Although exercise reconditioning is the key to a successful rehabilitation program, exercise training programs need to be adapted to the individual limitations of the COPD patient, taking into consideration cardiovascular, pulmonary, and skeletal muscle limitations. They note that exercises should be performed 3 to 5 days per week at an intensity above 40 to 85 percent of the oxygen uptake reserve (the difference between resting and peak oxygen intake) for more than 20 minutes per session. Contact: Cathy Carlomagno ###
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