Day: 12/02/2010

Pregnancy Loss Linked to Increased MI Risk Later in Life

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Women who’ve had recurrent miscarriages or a stillbirth may face elevated risk for myocardial infarction later in life, according to a prospective study in Heart.

Over 11,000 women (aged 35 to 66) who’d ever been pregnant were followed for roughly 11 years. During that time, 79 first MIs and 107 first strokes occurred. After adjustment for age and cardiovascular risk factors, women who reported having experienced more than three miscarriages had five times the risk for MI as those who’d never had a miscarriage. In addition, those reporting a stillbirth had more than three times the risk for MI, compared with those without a stillbirth.

There was no apparent association between pregnancy loss and stroke.

The authors say their findings are biologically plausible because many conditions that predispose to pregnancy loss also predispose to heart disease. They conclude: “Recurrent miscarriage and stillbirth … should be considered as important indicators for monitoring cardiovascular risk factors and preventive measures.”

 

Prostate Cancer Hormone Treatments May Raise Risk of Colorectal Cancer

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A large, retrospective population study suggests that prostate cancer treatments that lower male sex hormones may increase the risk of colorectal cancer. Men treated with gonadotropin-releasing hormone (GnRH) agonists or surgical removal of their testicles (orchiectomy) to lower their testosterone and PSA levels experienced an increased risk of colorectal cancer of about 20 to 40 percent. The findings were reported online November 10 in the Journal of the National Cancer Institute.

More than half of nearly 108,000 prostate cancer patients identified in the linked SEER-Medicare database received androgen deprivation therapy between 1993 and 2002. Approximately 90 percent of those men had been treated with GnRH agonists, and the rest had had orchiectomy. They were followed for about 5 years after their prostate cancer diagnosis.

After adjusting for possible confounders such as obesity, diabetes, and radiotherapy, the researchers found a dose-response effect for GnRH agonists in which colorectal cancer risk increased with longer duration of treatment. Compared with prostate cancer patients who received no hormone treatments, those who had GnRH agonist therapy for 13 to 25 months had a 19 percent increase in colorectal cancer risk, those who had GnRH agonist therapy for longer than 25 months had a 31 percent increase in risk, and those who had orchiectomy had a 37 percent increase in risk.

Lead author Dr. Silke Gillessen of Kantonsspital St. Gallen in Switzerland and her colleagues noted that an inverse association between androgen levels and colorectal cancer risk is biologically plausible. “Androgen receptors are present in both normal and malignant human colonic tissues, and in various animal studies, administration of androgens protects against colon carcinogenesis, whereas androgen ablation promotes it,” they wrote. The authors went on to say that their evidence “may have broader implications beyond the field of prostate cancer” because nearly half a million men in the United States develop androgen deficiency each year.

source: NCI

Advanced Cell Technology Receives FDA Clearance For the First Clinical Trial Using Embryonic Stem Cells to Treat Macular Degeneration

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Advanced Cell Technology announced today that the US Food and Drug Administration (FDA) has cleared the Company’s Investigational New Drug (IND) application to immediately initiate a Phase I/II multicenter clinical trial using retinal cells derived from human embryonic stem cells (hESCs) to treat patients with Stargardt’s Macular Dystrophy (SMD), one of the most common forms of juvenile macular degeneration in the world. The decision removes the clinical hold that the FDA had placed on the trial. Stargardt’s Macular Dystrophy causes progressive vision loss, usually starting in children between 10 to 20 years of age. Eventually, blindness results from photoreceptor loss associated with degeneration in the pigmented layer of the retina, called the retinal pigment epithelium (RPE). “There is currently no treatment for Stargardt’s disease,” said Dr. Robert Lanza, ACT’s Chief Scientific Officer. “Using stem cells, we can generate a virtually unlimited supply of healthy RPE cells, which are the first cells to die off in SMD and other forms of macular degeneration. We’ve tested these cells in animal models of eye disease. In rats, we’ve seen 100% improvement in visual performance over untreated animals without any adverse effects. Our studies showed that the cells were capable of extensive rescue of photoreceptors in animals that otherwise would have gone blind. Near-normal function was also achieved in a mouse model of Stargardt’s disease. We hope to see a similar benefit in patients with various forms of macular degeneration.” The Phase I/II trial will be a prospective, open-label study that is designed to determine the safety and tolerability of the RPE cells following sub-retinal transplantation to patients with advanced SMD. A total of twelve patients will be enrolled in the study at multiple clinical sites. The sites which are currently under consideration are the Jules Stein Eye Institute at UCLA (headed by Dr. Steven Schwartz); the Casey Eye Institute in Portland, Oregon (headed by Dr. Peter Francis of the Oregon Health Sciences University); the University of Massachusetts Memorial Medical Center in Worcester, Massachusetts (headed by Dr. Shalesh Kaushal, Chair of the Department of Ophthalmology); the UMDNJ – New Jersey Medical School in Newark, New Jersey (headed by Dr. Marco Zarbin, Chair, Institute of Ophthalmology and Visual Science); additional sites may be considered. Earlier this year the FDA also granted Orphan Drug designation for the company’s RPE cells. As a result, the company is eligible to receive a number of benefits, including tax credits, access to grant funding for clinical trials such as this one, accelerated FDA approval, and allowance for marketing exclusivity after drug approval for a period of as long as seven years. Raymond Lund, Ph.D., a scientific collaborator with ACT, and considered one of the world’s foremost experts in retinal cell physiology and vision restoration, commented, “The study results of ACT’s RPE cells implanted in the various animal models of macular degeneration was phenomenal. If ACT observes even a fraction of that benefit in humans, it will be nothing short of a home run.” “Initiating our macular degeneration clinical trial represents a significant milestone in the progress of developing human embryonic stem cell-based therapies aimed at large worldwide markets,” said William M. Caldwell IV, ACT’s Chairman and CEO. “I think generations will look back at this time as one of the most exciting in the history of medicine. With the initiation of this clinical trial, and that of Geron’s earlier this fall, the field of regenerative medicine is poised to take embryonic stem cell therapies from the realm of nebulous potential to that of tangible and real treatments that will make a significant difference in the lives of millions of people worldwide. This is truly a ‘game changer’ for the medical community.” Among the most common causes of untreatable blindness in the world are degenerative diseases of the retina. As many as thirty million people in the United States and Europe suffer from macular degeneration, which represents a $25-30 billion worldwide market that has yet to be effectively addressed. Approximately 10% of people ages 66 to 74 will have symptoms of macular degeneration, the vast majority the “dry” form of AMD – which is currently untreatable. The prevalence increases to 30% in patients 75 to 85 years of age. “These patient numbers are staggering in size,” stated Edmund Mickunas, ACT’s Vice President of Regulatory, “and when the impact on health and quality of life is considered in that context, macular degeneration represents one of the more significant unmet medical needs in our society. With the momentum of this Stargardt’s trial, and the unique experience we have gained as one of the few companies in the world having succeeded in taking an hESC program into the clinic, we are preparing to extend our lead with an IND in the use for treating age-related macular degeneration, as well as filing to begin clinical trials in Europe, in the very near future.”

Treatment of Influenza with Intravenous Peramivir

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Intravenous peramivir given within 48 hours of influenza symptom onset was well tolerated, reduced fever, and shortened time to resumption of usual activities.

To date, influenza treatments have consisted only of oral (oseltamivir) or topical (zanamivir) neuraminidase inhibitor formulations, but an intravenous option is also being investigated —the selective neuraminidase inhibitor peramivir. This sialic acid analogue is characterized by a strong affinity for influenza neuraminidase and a low off rate. Researchers recently reported the results of a manufacturer-sponsored, phase II, randomized controlled trial investigating the effect of a single dose of intravenous peramivir on the course of community-acquired influenza in previously healthy individuals during the 2007–2008 influenza season in Japan.

Within 48 hours after onset of typical influenza symptoms, 99 study participants received a 300-mg dose of peramivir, 97 received a 600-mg dose, and 100 received placebo. The clinical effectiveness of peramivir became evident within the first 24 hours after treatment initiation, and, by 36 hours, both the 300-mg and the 600-mg dose groups had significantly higher proportions of afebrile patients than the placebo group. Both peramivir groups also had a significantly shorter time to resumption of usual activities (median duration, 126 hours in the 300-mg group, 127 hours in the 600-mg group, and 169 hours in the placebo group) and to reduction of viral shedding; the three groups had similar viral titers at baseline, but by day 3, the proportion of virus-positive patients was significantly lower in the 300-mg group (37%) and the 600-mg group (26%) than in the placebo group (52%). Tolerability of peramivir was excellent.

Comment: Peramivir appears to be a promising new antiviral in the armamentarium against influenza and has already received FDA emergency-use authorization for the treatment of severe pandemic H1N1 influenza. Its intravenous formulation makes it particularly attractive for treating severely ill patients, but dose-finding trials have not yet been completed in this population. Animal studies indicate that multiple doses of peramivir for up to 15 days might be appropriate for such patients.

— Thomas Glück, MD

Published in Journal Watch Infectious Diseases December 1, 2010