The Research Pipeline
Anelixis clinical portfolio contains the following assets:
CD40 Ligand (CD40L):
Amyotrophic lateral sclerosis (ALS) is a progressive neurological disorder characterized by muscle fiber atrophy resulting from the degeneration of motor neurons in the spinal column and
brain. Though ALS is characterized by loss of motor neurons in the spinal cord resulting in muscle atrophy, the disease also manifests itself with changes in axon transport, protein mis
folding, excitotoxicity, neuroinflmamation, mitochondrial dysfunction, and synaptic remodeling.
Neuroinflammation in the central and peripheral nervous system with infiltration of activated monocytes and T lymphocytes is an accepted pathophysiology associated with ALS animal models
and patients. Although the role of infiltrating immune cells is poorly understood recent work would suggest that infiltrating T cell populations are neuroprotective and not cytotoxic
however the role of infiltrating monocytes is less well understood.
It is generally accepted that two signals from antigen presenting cells (APCs) are required for maximal T cell activation and that this activation pathway is called the Costimulatory
Pathway. These two signals are the engagement of the T Cell Receptor (TCR) on T cells with antigen bound Major Histocompatibility Complex (MHC) on antigen presenting cells (APCs) and
the binding of activating ligand and their cognate B7 receptors on T cells and APCs respectively. The activation of APCs and up regulation of the B7 receptors and MHC molecules is
sufficient to activate T cells and induce a humoral immune response.
In addition to the B7 receptors the Tumor Necrosis Factor (TNF) family member CD40 is up regulated on APCs after activation by foreign antigens. CD40 is expressed on mature B cells,
macrophages, and dendritic cells. The receptor for CD40, CD40L (CD154, gp39) is a Type I membrane receptor and a member of the TNFR superfamily. CD40L expressed on activated T cells
as a result of antigen presentation. CD40 ligation induces expression of adhesion molecules and costimulatory molecules on APCs such as CD44, ICAM1, ITGAX (CD11c ), CCL3 (Mip1);
Fcgr2b (CD32); ITGAM (CD11b); ITGB2 (LFA1/CD18) and MHC class II molecules.All intellectual property regarding the role of CD40L in ALS that has been issues to ALS TDI has been l
icensed to Anelixis Therapeutics
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