Drug Information Bulletin

Drug Information Centre (DIC) Indian Pharmaceutical Association

Bengal Branch Tele fax: 033 24612776, E-mail: ipabengal.dic@gmail.com Web Site: http://www.ipabengal.org Contact: 09830136291

th

Year

Volume: 05

Number: 44

12th February 2012

Content EU, India trade talks may threaten India's ability to bring drugs tow world's poor Zinc plus antibiotics may reduce fatalities in some children with Pneumonia Some patients taking Bisphosphonates may experience unusual femur fracture Health ministry seeks Rs.5825 crore for implementing revised national TB control programme Scientists find gene therapy for inherited blindness succeeds in patients' other eye Zinc plus antibiotics may reduce fatalities in some children with Pneumonia Medscape reports, "In a study conducted in Africa, children aged six to 59 months who had severe pneumonia had reduced mortality when receiving zinc in addition to standard antibiotics." In the study published in BMC Medicine, researchers found that "among HIV-infected children, case fatality was seven of 27 children in the placebo group vs 0 of 28 children in the zinc group (RR, 0.1; 95% CI, 0.0 1.0). In contrast, in HIV-uninfected children, no difference in case fatality was observed with zinc vs placebo: case fatality was 7/127 (5.5%) with placebo vs 5/129 (3.9%) among HIV-uninfected children receiving zinc (RR, 0.7; 95% CI, 0.2 2.2)."

EU, India trade talks may threaten India's ability to bring drugs tow world's poor The AP reports, "Efforts by India and the European Union to strengthen trade are threatening India's ability to deliver lifesaving medicines to the world's poorest, analysts say as the two sides push through protracted negotiations on a free-trade pact." The AP adds, "India's prime minister and top EU officials are hoping their summit Friday in New Delhi helps move beyond disagreements over issues like European labor market limits and Indian duties on cars." However, "health industry workers and activists worry that India may bow to EU demands for strict intellectual property protections and investor guarantees, which could close down the world's generic drug supply."

2 Some patients Bisphosphonates may unusual femur fracture taking experience and at least 85 per cent of previouslytreated TB patients, reduction in default rate of new TB cases to less than 5 per cent and re-treatment TB cases to less than 10 per cent, and initial screening of all re-treatment smear-positive cases till 2015 and all smear positive TB cases by year 2017 for drug-resistant TB and provision of treatment services for MDR-TB patients. It will also seek to offer of HIV counseling and testing for all TB patients and linking HIV-infected TB patients to HIV care, and support and extension of RNTCP services to patients diagnosed and treated in the private sector. To achieve the objective of universal access to TB care and complete coverage of MDR services, key strategies and innovative approaches proposed under RNTCP include intensified case finding activities in high risk groups like smokers, diabetics, malnourished, HIV, urban slums and difficult to reach areas etc., development of a dedicated sputum collection and transport system across the country to all health facilities (including PHCs without DMCs), and improved surveillance by case-based electronic notification systems and data quality assurance. Establishing referral linkages between Primary Health Centres with secondary and tertiary hospitals for diagnosis of extrapulmonary TB cases and paediatric TB cases, conducting prescription audits in private and public sectors, regular drug resistance surveillance, and use of telecommunication in demand generation, service delivery and patients tracking will also form part of the strategies. Scientists find gene therapy for inherited blindness succeeds in patients' other eye

WebMD reports that according to a study presented at the Annual Meeting of the American Academy of Orthopedic Surgeons, a small number of patients who take bisphosphonates "may experience an unusual femur (thighbone) fracture if they take the drugs on a long-term basis." Researchers noted, however, that far more fractures are being prevented than caused. Professor Joseph Lane, MD, "who was not involved in the research, recommends that patients taking bisphosphonates stop after five years for a drug holiday. Then he tests the patients to see how dense their bones are and does additional tests to help determine if there is a need for further bisphosphonate therapy." Health ministry seeks Rs.5825 crore for implementing revised national TB control programme The health ministry has sought Rs.5825 crore for the implementation of the revised National TB Control Programme (RNTCP) during the next five-year plan period to ensure the universal access to TB care in the country. Since its inception, the RNTCP has evaluated over 44 million persons for TB and initiated treatment for over 12.8 million TB patients and has saved more than 2.3 million lives. The Annual Risk of TB Infection (ARTI) has reduced from 1.5 per cent to 1.1 per cent and prevalence has also reduced from 316 per lakh population in 2007 to 266 per lakh population in 2010, according to the proposal by the ministry to the Planning Commission. The objectives for 12th Plan include early detection and treatment of at least 90 per cent of estimated TB cases in the community (all types) including TB associated with HIV, successful treatment of at least 90 per cent of new TB patients,

3 Gene therapy for congenital blindness has taken another step forward, as researchers further improved vision in three adult patients previously treated in one eye. After receiving the same treatment in their other eye, the patients became better able to see in dim light, and two were able to navigate obstacles in low-light situations. No adverse effects are occurred. Neither the first treatment nor the readministered treatment triggered an immune reaction that cancelled the benefits of the inserted genes, as has occurred in human trials of gene therapy for other diseases. The current research targeted Leber congenital amaurosis (LCA), a retinal disease that progresses to total blindness by adulthood. Scientists from The Childrens Hospital of Philadelphia and from the Perelman School of Medicine at the University of Pennsylvania led the study, published in Science Translational Medicine. Patients have told us how their lives have changed since receiving gene therapy, said study co-leader Jean Bennett, MD, F.M. Kirby professor of Ophthalmology at Penn. They are able to walk around at night, go shopping for groceries and recognize peoples faces - all things they couldnt do before. At the same time, we were able to objectively measure improvements in light sensitivity, side vision and other visual functions. Other objective results came from brain signals seen in neuroimaging. When a dimly flickering checkerboard pattern flashed in front of a patients recently treated eye, an area in the brain responsible for vision lit up during functional magnetic resonance imaging (fMRI).This finding is telling us that the brain is responding to the eyes sensitivity to dim light, said radiology researcher Manzar Ashtari of The Childrens Hospital of Philadelphia, the studys co-leader. LCA is a group of hereditary retinal diseases in which a gene mutation impairs production of an enzyme essential to light receptors in the retina. The study team injected patients with a vector, a genetically engineered adeno-associated virus, which carried a normal version of a gene called RPE65 that is mutated in one form of LCA. The researchers in the current study previously carried out a clinical trial of this gene therapy in 12 patients with LCA, four of them children aged 11 and younger when they were treated. Exercising caution, the researchers treated only one eye - the one with worse vision. This trial, reported in October of 2009, achieved sustained and notable results, with six subjects improving enough to no longer be classified as legally blind. The Centre for Cellular and Molecular Therapeutics (CCMT) at The Childrens Hospital of Philadelphia sponsored both the initial clinical trial and the current study, and manufactured the vector used to carry the corrective gene. Katherine A High, a co-author of both studies, is the director of the CCMT, and a pioneering gene therapy researcher. The research teams experiments in animals had showed that re-administering treatment in a second eye was safe and effective. While these results were encouraging, the researchers were concerned that re-administering the vector in the untreated eye of the patients might stimulate an inflammatory response that could reduce the initial benefits in the untreated eye. Our concern was that the first treatment might cause a vaccine-like immune

4 response that could prime the individuals immune system to react against a repeat exposure, said Bennett. Because the eye is immune-privileged relatively isolated from the bodys immune systemsuch a response was considered less likely than in other parts of the body, but the idea needed to be tested in practice. As in the first study, retina specialist Albert M Maguire, MD, a study co-author, injected the vector into the untreated eyes of the three subjects at The Childrens Hospital of Philadelphia. The patients had been treated one and a half to three years previously. The researchers continued to follow the three patients for six months after readministration. They found the most significant improvements were in light sensitivity, such as the pupils response to light over a range of intensities. Two of the three subjects were able to navigate an obstacle course in dim light, as captured in videos that accompanied the published study. There were no safety problems and no significant immune responses. There was even an unexpected benefitthe fMRI results showed improved brain responses not just in the newly injected eye, but in the first one as well, possibly because the eyes were better able to coordinate with each other in fixating on objects. The researchers caution that follow-up studies must be done over a longer period and with additional subjects before they can definitively state that re-administering gene therapy for retinal disease is safe in humans. However, said Bennett, the findings bode well for treating the second eye in the remaining patients from the first trialincluding children, who may have better results because their retinas have not degenerated as much as those of the adults. Furthermore, Bennett added, the research holds promise for using a similar gene therapy approach for other retinal diseases. Ashtari said that fMRI may play a future role in helping to predict patients more likely to benefit from gene therapy for retinal disease. Funding support for this study came from the CCMT, the Foundation Fighting Blindness-sponsored CHOP-PENN Paediatric Centre for Retinal Degenerations; the National Institutes of Health (National Centre for Research Resources grants UL1-RR-024134, IR21EY020662, and 1R01EY019014-01A2), Research to Prevent Blindness, Hope for Vision, the Paul and Evanina Mackall Foundation Trust at the Scheie Eye Institute, anonymous donors, the Italian Telethon Foundation, and the FM Kirby Foundation. Dr High is an Investigator of the Howard Hughes Medical Institute, which also provided support. AAV2 Gene Therapy Re-administration in Three Adults with Congenital Blindness, Science Translational Medicine, Feb. 8. Penn Medicine is one of the worlds leading academic medical centres, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. The University of Pennsylvania Health Systems patient care facilities include: The Hospital of the University of Pennsylvania - recognized as one of the nation's top 10 hospitals by US News & World Report; Penn Presbyterian Medical Centre; and Pennsylvania Hospital the nation's first hospital, etc. Subscribe / Unsubscribe Mail to: ipabengal.dic@gmail.com