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PipelineCognosci Inc. is focused on development of drugs to treat diseases with a pharmacogenomic linkage to the apolipoprotein E (apoE) protein including Multiple Sclerosis, Alzheimer's Disease, and Traumatic Brain Injury. For most of these diseases, people with the 4 allele of apoE typically suffer worse outcomes. Scientists from Cognosci have created and optimized novel apoE-based compounds with potent anti-inflammatory and neuroprotective activities using more than $7.5 million in Phase I and Phase II Small Business Innovation Resource (SBIR) grants from the National Institutes of Health. These funds have been used to identify lead candidates for each of the diseases described below with projects ranging from lead identification to full preclinical development programs. Current Leads
Multiple Sclerosis
Multiple Sclerosis (MS) is widely recognized as an autoimmune disorder that poses a significant medical challenge. Autoimmune disorders occur when the immune system, which normally functions to fight viral and bacterial challenges, undergoes aberrant activation to recognize human proteins as antigens. This aberrant activation results in attack of the immune system on structures in the body rather than invading infective agents. In the case of MS, one of the antigens is the myelin protein that insulates nerve fibers in the brain and spinal cord, which leads to destruction of the myelin sheath. Myelin is critical for nerve signaling and it's destruction results loss of nerve signal conductance and eventually, to nerve cell death. The neurodegeneration caused by the immune attack results in a progressive loss of neuromuscular control, increasing disability, and eventually death.
Histopathological Analysis: COG133 prevented spinal cord demyelination in MOG-induced EAE mice. The animals were sacrificed 30 days after MOG immunization and the whole spinal cord was dissected out and 5- m -thick sections were made from cervical segments of COG133-treated animals (B) and Normal Saline treated ones (A). These sections were stained with Luxol fast blue (for myelin, stained in blue) and then counterstained with eosin (showing peripheral infiltrates, in purple). The ability of the Cognosci compounds to reduce disability is derived from suppression of inflammation, protection of damaged neurons from endogenous neurotoxins release by degeneration of myelin producing cells, and promoting remyelination of damaged neurons. The anti-inflammatory effects are driven by inhibition of microglial activation, reducing secretion of proinflammatory cytokines, and suppression of nitric oxide production in both peripheral tissues and in the CNS (see left panel below; Laskowitz et al. 2001 for in vitro studies and Lynch et al. 2003 for in vivo studies). These compounds also protect neurons from NMDA excitotoxicity (see graph below; Aono et al. 2003).
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Latest News Cognosci Receives Funding for Advanced Testing of Lead Drug Candidate for the Treatment of Multiple Sclerosis For more information, contact:
Cognosci Inc. |
Cognosci has developed the first neuro-restorative compounds for treatment of Multiple Sclerosis that display a significant reduction of disability in animal models of MS. These compounds are small synthetic peptides of ten to seventeen amino acids that are based on the multifunctional apoE protein, and have potent in vitro and in vivo anti-inflammatory activity. In addition to inhibiting inflammation, Cognosci's "COG" compounds also directly protect nerve cells by blocking activity of endogenous neurotoxins released by injured brain cells. In the case of Multiple Sclerosis, the dual actions (immune suppression and direct neuroprotection) of our lead compounds are further bolstered by neuro-reparative activity where the compounds promote repair of damaged nerve cells to restore normal function.
