Society For Neuroscience

News from the 31st annual meeting of the Society for Neuroscience in San Diego:

¿ Acadia Pharmaceuticals Inc., of San Diego, reported the successful application of its chemical genomics platform to discover compounds that differentiate between insect and human genomic targets. Acadia scientists reported that they discovered compounds that are potent and highly selective for a specific insect G protein-coupled receptor. The company said this demonstrates the utility of Acadia¿s platform in the discovery of novel chemistries for various applications where differentiation between mammalian and nonmammalian targets is desired, such as agriculture and infectious disease.

¿ Cephalon Inc., of West Chester, Pa., said studies conducted by partner, H. Lundbeck A/S, of Copenhagen, Denmark, demonstrated that CEP-1347 improves the survival of transplanted dopamine neurons in a preclinical model of Parkinson¿s disease. The study was designed to test whether CEP-1347, a semi-synthetic compound shown to protect multiple nerve cell types from a variety of insults leading to programmed cell death, could improve the survival of dopamine neurons prior to and after transplantation. Out of 36 rats, one group was treated with CEP-1347 prior to transplantation, while a control group received placebo. At least 300 percent more transplanted dopamine neurons survived when treated with CEP-1347 as compared to untreated transplants.

¿ Incara Pharmaceuticals Corp., of Research Triangle Park, N.C., said its investigational catalytic antioxidant, AEOL 10150, was shown to significantly reduce brain damage in a standard mouse model of stroke. AEOL 10150 administered intravenously after the obstruction of blood flow significantly reduced cortical and subcortical infarct volume, improved neurological recovery and modulated changes in gene expression and protein synthesis induced by the experimental stroke injury. Incara¿s catalytic antioxidant molecules inactivate reactive oxygen species, such as superoxide, hydrogen peroxide and peroxynitrite.

¿ Vasogen Inc., of Toronto, released new findings demonstrating the ability of its immune modulation therapy to significantly reduce key measures of inflammation and cell death in the brain and to improve physiological measurements that correlate with memory and learning. The preclinical research was conducted at Trinity College in Dublin, Ireland. In the cerebral cortex of the brain, the immune modulation therapy led to a significant decrease (p<0.05) of reactive oxygen species, key mediators of inflammatory responses and cell death, as well as a decrease (p<0.05) in the expression of certain enzymes involved in the intracellular response to inflammation, among other findings. Results from studies performed on the hippocamus also demonstrated that the therapy can significantly reduce cell death (p<0.01) and is associated with an increase (p<0.05) in the anti-inflammatory cytokine IL-10.

American College of Rheumatology

News from the Scientific Meeting of the American College of Rheumatology conference in San Francisco:

¿ Alexion Pharmaceuticals Inc., of Cheshire, Conn., presented clinical safety, efficacy and biological data from a Phase II trial of 5G1.1 in rheumatoid arthritis patients. The data showed that the primary endpoint of improvement in ACR (American College of Rheumatology) 20 score was successfully met in one of the 5G1.1 treated groups after three months of treatment. Data from the double-blind, randomized, placebo-controlled trial also showed that 5G1.1 administration was associated with a dose-dependent improvement in ACR20 score in a subset of patients with elevated baseline levels of terminal complement activation. The study enrolled 209 patients at 28 U.S. clinical sites.

¿ Celgene Corp., of Warren, N.J., presented data on a preclinical study of novel small-molecule IkB kinase-2 (IKK-2) inhibitor CDC 839/AS602868. When evaluated in an in vivo model of rheumatoid arthritis, CDC 839 significantly reduced joint inflammation and destruction. The data demonstrated that IKK-2 inhibitors may have significant disease-modifying potential in treating rheumatoid arthritis.

¿ Human Genome Sciences Inc., of Rockville, Md., reported data that support the potential of LymphoStat-B, a human monoclonal antibody targeting BLyS (B lymphocyte stimulator), as a treatment for autoimmune diseases, such as systemic lupus erythematosus, rheumatoid arthritis and Sjogren¿s syndrome. Results of one study showed that serum and synovial (joint) fluid BLyS levels in patients with inflammatory arthritis were significantly greater than BLyS levels in the serum or synovial fluid of patients with osteoarthritis or traumatic arthritis (p<0.0001 and 0=0.043, respectively). Another study showed that measurements of serum from 49 patients demonstrated that BLyS levels were significantly increased in patients with Sjogren¿s syndrome as compared to control patients (p<0.0001).

¿ La Jolla Pharmaceutical Co., of San Diego, presented data from an earlier Phase II/III clinical trial indicating that treatment with LJP 394 appeared to be as effective as current immunosuppressive therapy in reducing antibodies to double-stranded DNA that are believed to be responsible for lupus renal disease. These findings were from a Phase II/III study of more than 200 patients with lupus renal disease who were treated for up to 18 months with LJP 394 or placebo. In previous clinical trials, LJP 394 was shown to specifically reduce antibodies to double-stranded DNA and appeared to be well tolerated.

¿ Regeneron Pharmaceuticals Inc., of Tarrytown, N.Y., released preliminary results from a Phase I trial of its Interleukin-l Cytokine Trap. The study is assessing the safety and tolerability of IL-l Trap in patients with rheumatoid arthritis, and results indicate that it generally was well tolerated and displayed a favorable safety profile. Based on the results, Regeneron plans to begin Phase II studies with the IL-l Trap and to begin clinical trials of two additional product candidates from its custom-designed Trap platform.

American Heart Association

News from the annual meeting of the American Heart Association¿s Scientific Sessions 2001 in Anaheim, Calif.:

¿ AVI BioPharma Inc., of Portland, Ore., demonstrated that stents coated with its NeuGene antisense compound Resten-NG (AVI-4126) significantly reduced coronary restenosis. The preclinical study results also showed AVI-4126-coated stents healed almost as quickly as those treated with uncoated stents. Arteries treated with stents coated with dactinomycin (Cosmegen or actinomycin-D) and paclitaxel (Taxol) healed much more slowly, AVI said.

¿ Corgentech Inc., of Palo Alto, Calif., said a Phase IIb trial, known as the Prevent 2 trial, demonstrated that its lead product candidate, E2F Decoy ¿ an oligonucleotide ¿ significantly reduced graft failure following coronary artery bypass graft surgery. Additional intravascular ultrasound data generated in the study showed grafts treated with E2F Decoy did not have the same wall thickening and intimal hyperplasia observed in the untreated vein grafts. The new treatment decreased the overgrowth of the graft wall that occurs after bypass operations from a mean of 115 mm3/cm to 79 mm2/cm.

¿ Valentis Inc., of Burlingame, Calif., said results of a 54-patient Phase II trial showed the VEGF165 gene, which is incorporated into one of Valentis¿ lipid delivery systems, can induce angiogenesis in the legs of patients with peripheral arterial disease. The randomized, double-blind, placebo-controlled trial also demonstrated that the VEG165 gene delivered with Valentis¿ lipid delivery system was as effective as the VEGF165 gene delivered by an adenoviral vector. Additionally, the safety issues associated with adenoviral vectors were not seen in patients receiving the gene delivered with the system.

Study Of Liver Diseases

News from the 52nd annual meeting of the American Association for the Study of Liver Diseases in Dallas:

¿ Enzo Biochem Inc., of New York, reported the results of a preclinical study in which its oral immune regulation medicines were used to suppress liver cancer cell growth in experimental animals. Human liver cancer cells were implanted into mice with no immune system and the mice were then transplanted with immune cells from nontreated donor mice. After transplantation, the recipient mice were divided into three groups. All the mice treated with the tumor cell medicine and about 28 percent of the mice treated with the HBV proteins survived. None of the control mice treated with bovine serum albumin survived.

¿ Gilead Sciences Inc., of Foster City, Calif., reported data from Study 435 of adefovir dipivoxil 10 mg once daily in post-liver transplant patients with lamivudine-resistant chronic hepatitis B virus infection. Treatment with adefovir dipivoxil 10 mg once daily for 48 weeks resulted in a statistically significant decrease in HBV DNA of 4.6 log¹⁰ copies/mL (n=28). At baseline, patients had a median serum HBV DNA of 8.2 log¹⁰ copies/mL.