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Genomic Screens for Longevity Therapeutics

Genescient has a proprietary screen for substances that can extend human lifespan and healthspan. Using genetically selected long lived Drosophila (Fig. 1) and the latest genetic tools, Genescient has identified over 100 gene networks (∆’s) that are altered in long lived strains of Drosophila melanogaster and that are also linked to longevity and age-related diseases in humans (Fig. 2).
Fly Mortality Data
Fig. 1: Selected Long Lived Drosophila
Genescient overlapping Genes
Fig. 2: Genetic Overlap → Human Longevity Genes
 
Using our 100 proprietary longevity gene pathways, combined with the public data on human gene dysfunction associated with age-related disease, we have identified Designer Therapeutics δ**’s for the genetic pathways controlling aging (Fig. 3). In selecting compounds to test, we search the published literature for compounds that act on one or more of our proprietary genetic pathways of aging. Genescient has sophisticated software that cross links gene function in Drosophila with possible human therapeutics for age-related diseases. Drosophila is an excellent model system of aging and age-related disease that has many genetic pathways that are highly conserved in humans. Therefore, therapeutic substances that act on genetic pathways in Drosophila often work similarly in humans.
Genescient nutrigenomic screen
Fig. 3:  Genescient Uses 100 Longevity Genes (∆’s) as Targets to Screen for Therapeutics (δ**’s)
 
We focus on gene functional relations to human physiology and age-related diseases. This highlights various networks of pathways and genes described in the literature. We then make maps of networks pointing to the genes appearing in our proprietary list and their relationships. This elucidates possible human therapeutics to treat chronic diseases of aging and improve function.

Once found, we then quickly test these compounds in Drosophila for their effects on median lifespan, background mortality, and the rate of aging at different doses. Later Drosophila tests focus on fertility and mating success to determine the functional vitality of the Drosophila with increased lifespan and to test for any potential side effects of each therapeutic substance.

Because the selected Drosophila genetic pathways are also linked to conserved age-related disease genes in humans, direct therapeutic effects on human health can be expected. In our first attempts at selection using this screening procedure, we have already initially tested 13 compounds on normal flies. We found 12 that extend significantly the normal Drosophila lifespan, reduce background mortality rates, or slow the rate of aging. The thirteenth was a null test: we used a compound that acts in humans but not in Drosophila, and as expected, the flies did not respond. Two of the substances that passed our initial tests have also passed our functional tests for fertility and mating-success; we are now performing additional tests of this type on the other promising substances.

The speed and efficacy of our Drosophila testing allows us to test various combinations of compounds to acquire a highly synergistic set of compounds that act through differing aging pathways. This adds greatly to the therapeutic efficacy of the final treatment. Slowing the aging process requires several compounds, acting on several genetic pathways simultaneously. Our screening procedure allows us to identify quickly the best combinations of compounds that can act simultaneously on multiple genetic networks (cardiovascular, metabolic, neurological, etc).

When we find a multipath set of therapeutic compounds, we then do final nutrigenomic testing in humans. We establish dosage levels by prior literature data and our own testing. Once a group of 3 to 4 nutrigenomic compounds has been identified as synergistic in Drosophila, we can evaluate therapeutic efficacy of the nutrigenomic combination in humans using clinical tests such as: athletic performance, cognitive performance, lung capacity, skin elasticity, blood lipids, serum glucose, as well as inflammatory markers like CRP and IL-6. For any particular age-related disease, our proprietary therapeutic compounds could also be tested in specific disease mouse models or in human clinical trials.

Genescient’s Designer Therapeutics fine tune the body’s gene expression to mimic genetically selected longevity and reduced all cause mortality. This approach is in marked contrast to competing Pharma and biotech companies that focus on a single age-related disease or disorder. Genescient is the first company to develop genetic Designer Therapeutics to delay aging and the age-related diseases.

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For more information, a copy of Genescient's business plan, or a detailed description of Genescient's technology please contact us at info at genescient dot com, or at +1 949.244.2862.

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