Neurogenesis
Adult neurogenesis refers to the formation of new neurons in the brain of an adult organism. Neurogenesis occurs in discrete regions of the adult mammalian brain, particularly in the hippocampus, a area particularly vulnerable to Alzheimer’s disease. Hippocampal neuronal cells in the adult are formed from proliferating neuronal progenitor cells, and these new neurons form functional connections.

Drug screening and development for neurogenesis with KineMed technology
With the KineMarker™ method, cell proliferation in the brain is measured from the synthesis of new DNA and new cells with heavy water (²H₂O). Measuring the proliferation of the progenitor cell population is an indicator of neurogenesis.

Potential applications include the assessment of neurogenic effects of drugs being developed for Alzheimer’s disease, stroke, traumatic brain injury, as well as agents for learning and memory. Survival and differentiation of progenitor cells into neurons was assessed by a pulse chase protocol.

Hippocampal progenitor cell proliferation serves as the initial screen for neurogenesis. Compounds that show a positive response (increase) will be further characterized with dose response studies, testing other agents in class, as well as assessing efficacy in combination with other agents.

In addition to assessing drugs approved for mood and/or cognitive disorders, we tested drugs approved for other indications and discovered novel agents that increase cell proliferation in the hippocampus. The effectiveness of these drug compounds has been further confirmed with dose-response studies.

Neurodegeneration: ALS
ALS (or Lou Gehrig's disease) is a rapidly progressive, invariably fatal neurological disease that attacks neurons that control the voluntary muscles.

Familial ALS patients have mutations in a gene called SOD1.

Through KineMed's work with the transgenic SOD1 mouse model of human ALS, KineMed has identified a critical imbalance of a key metabolic pathway in the motor neurons-the turnover of tubulin, an important component of the cytoskeleton, into microtublues. This kinetic imbalance results in disruption of the flow of neurotransmitters and nutrients along the axon, which leads to neuronal dysfunction and irreversible damage.

Drug screening and development for ALS
The development of a drug screen for ALS has been hindered by the lack of an identified mechanism to target and a specific biomarker of neuronal dysfunction.

KineMed's unique technology allows it to screen drug candidates that modify changes in the dynamics of microtubules in the ALS model and thus correct the kinetic imbalance before neuronal damage occurs.

With its unique mechanistic insights, KineMed's ALS/neurodegeneration program has identified and filed IP on two active ALS drug candidates that have demonstrated human safety. KineMed is working to complete its IND-enabling studies and file an IND in 2008.

KineMed's translational medicine may provide an opportunity to confirm this mechanistic approach in patients. KineMed's lead compounds are eligible for Fast-Track and Orphan Drug protection in ALS. Additionally, the company is pursuing expansion of this mechanistic approach to Parkinson's disease, Alzhiemer's disease and other neuropathy indications.