Friday, June 16, 2006

CD40:CD40L as a target for Alzheimers...A new candidate oncology therapeutic to enter the clinic

Todays Headlines from across the DailyUpdates network. In today's edition (see it in full) we report on CD40:CD40L. Traditionally a target for autoimmune/transplant therapeutics, we highlight a study supporting the development of blockers of CD40:CD40L as candidate treatments of Alzheimer's disease. We also highlight a new oncology candidate in development by Lorus
  • Breaking News (from DailyUpdates-Oncology): Locus Pharmaceuticals about to enter the clinic with novel cell cycle regulator Cell cycle inhibitors represent a key approach to the treatment of cancer. Therapeutic agents have traditionally targeted early stages of the cell cycle (ie the G1/S phase checkpoint or the S phase) or mitotic spindle formation as exemplified by the alkaloids. Recently drug development activity has started to focus on later stages of the cell cycle from the G2/M check point all the way through to the mitotic checkpoint and late mitosis. We recently evaluated one molecular target which shows great promise as a target for therapeutic agents able to modify later stages of the cells cycle, the aurora kinase family (see Aurora Kinase inhibitors - The dawn of a new approach to cancer). Here we feature news from Locus Pharmaceuticals who have been targeting tubulin as a strategy for blocking the cell cycle. Tubulin has been well recognized as a target for the taxanes. Locus’ candidate, LP-261, which will hopefully soon be moving into the clinic interacts with tubulin at a unique binding site. Unlike the taxanes, LP-261 shows excellent oral bioavailability and it is also effective in cancer cells that are resistant to taxol, vinblastine and Gleevec. LP-261 does not appear to be a substrate for MDR [Source: Locus Press Release]
  • Featured Journal Article (from DailyUpdates-Neurodegenerative Disorders): CD40:CD40L (CD154) - A target for Alzheimer's disease: Alzheimer's patients remain poorly treated and are growing in number. Currently, cholinesterase inhibitors and the more recent NMDA-receptor antagonists provide only moderate and temporary symptomatic benefit. By the end of the decade, however, novel drugs with the ability to slow the rate of disease progression are expected to be launched (see Pipeline and Commercial Insight: Alzheimer's Disease). One new target for the treatment of Alzheimer's is CD40L (CD154). This T-cell molecule binds to CD40 on antigen presenting cells and plays a key role in T-cell coactivation and hence the drug development sector has been developing blockers of CD40L:CDL as treatments of autoimmune disorders (see Autoimmune Disorders & Transplant Rejection - The Potential of T-cells Targeted Therapeutics). CD40L:CD40 interaction is thought to regulate microglia in the brain of patients with Alzheimer’s disease thus modifying Abeta phagocytosis and the production of inflammatory mediators. Although studies have shown that blocking CD40L reduces Abeta deposition and improves cognition in models of Alzheimer’s, the effect of CD40 blockade has not been directly investigated. This is important with respect to target selection as CD40L can also bind GPII/III on the surface of platelets. Today’s featured study reports that as with CD40L, CD40 deletion also prevents the development of Alzheimer's disease-like pathology. Thus blocking either CD40 or its ligand may be of therapeutic interest and indeed the blockade of the former may be preferable as cardiovascular adverse effects may be reduced [Source: J Neuroinflammation. 2006 Feb 24;3:3.]


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