Winter Quarter

1. Work continues on a paper that describes our transgenic Alzheimer’s fly model and the human pilot study we conducted as a result of studies using that model.
2. Some preliminary data analysis of the MX100a patient registry, which has grown to over 150 individuals, shows that the human pilot results are in fact being replicated, and patients’ cognitive and functional test scores are stable, or improving.
3. NOTE: The registry data is not a controlled trial, and can only be looked at in terms of trends.

Spring, Summer Quarters

1. Wrapping up our paper describing our transgenic Alzheimer’s fly model and the resulting human pilot study.

Fall Quarter

1. After Thanksgiving, we decided to divide the paper into two separate papers: a paper describing our transgenic Alzheimer’s fly model, and a paper describing the human pilot testing our formulation.
2. The transgenic fly paper is submitted to the Journal of Biology and Medical Research in December.

Winter Quarter

1. Our Gen31 experiment assays the transgenic Tau Alzheimer’s Disease (AD) flies and our “B” flies with MX100a, memantine (Namenda), and combinations of the two therapies.
2. Memantine (Namenda), is one of only a few “first line” therapies used to treat AD. Genescient made the decision to test memantine using our fly model to validate the model and verify our results to date.
3. We observed that memantine did indeed reduce symptoms in our transgenic Tau flies, thus helping to validate our platform for testing of AD treatments.
4. We saw the most positive results with the co-therapy of MX100a and memantine, suggesting a possible synergistic effect, and a possible avenue for us to explore potential collaborations.
5. Genescient enlists te help of Bob Cruise, Ph.D., to help with our analysis of the human pilot data.
6. We find that Memex seemed to help people with the ApoE4 genotype associated with the onset of AD.

Spring Quarter

1. During our continued analysis of the human pilot data, we compare our data to a study titled “Age and Rate of Cognitive Decline in Alzheimer Disease” by Charles Bernick, et. al., that analyzed 471 AD patients “mild to moderate AD assigned to the placebo arm of 3 clinical trials.”
2. Our patient trajectories are positive compared to the placebos in the Bernick paper, suggesting that MX100a has a positive effect on AD patients.

Fall and Winter Quarter

1. The MX100a patient registry has continued to grow to over 200 participants.
2. The patients appear to be stabilizing, and Dr. Shankle continues to recommend MX100a to all of his patients.
3. At this time, it’s the further fortified MX100a+ that the patients are taking.
4. Genescient begins work on a paper to report our results with the transgenic AD flies and subsequent human pilot study.

Winter Quarter

1. Dr. Robin Mockett, at University of Alabama, confirmed the longevity benefits of MX-100 on his fruit flies under certain conditions.
2. We begin writing the MX-100 paper, reporting these longevity results, with the goal of submitting to Plos One.
3. The Genescient Lab begins planning transgenic fly experiments with the 9 genes that we think make the O Flies live so long, according to our AI analysis. We also plan on testing the transgenic AD flies.
4. Preliminary testing is done to sort out the crawl test procedure and induction of A-beta in transgenic AD flies using RU486 (Mifpristone).
5. Dr. John Tower of USC has told us that other transgenic flies, ie with our longevity genes, should also be inducible with RU4486.

Spring Quarter

1. We have acquired, increased numbers, and maintained our targeted transgenic fly lines: 9 “O” longevity genes, transgenic AD flies carrying Tau, and transgenic AD flies carrying Abeta.
2. A new stress test is planned (on B flies) testing substances known in literature to act on the “O” genes.
3. Our preliminary AD fly crawling assays show that selenium, genestein (low and high dose), lithium, HCTZ, tretinoin, silymarin, and MX-100 all mitigate AD symptoms in transgenic flies with ABeta and Tau genes.

Summer Quarter

1. Our Gen18 stress test assays 13 new substances and compares them to the effects of MX-100.
2. The goal of Gen18 is to decide what should be added to MX-100 to make a novel and effective AD treatment to test using the transgenic AD fly model.
3. These results are another proof of concept for Ben Goertzel’s AI selection techniques, as the substances selected seem to be successful.
4. Our Gen19 experiment is a replicate of Dr. Robin Mockett’s protocol with MX-100, and we plan to include the results in the Plos One paper. Dr. Mockett’s protocol has flies living in vials instead of cages, and separated by sex. We are able to replicate his results: fly longevity is extended greatly in sex separated vials treated with MX-100.

Fall Quarter

1. Our Gen20 experiment tests the effects of RU induction on our 9 “O” longevity genes. If the genes are properly induced, the flies should live longer.
2. We find 2 out of the 9 genes significantly increase longevity when induced with RU, a “good” discovery rate using our machine learning and AI methods.
3. Our Gen21 experiment is a stress test assaying MX-100, individual components of MX-100, synthetic versions of components of MX-100, and some different combinations of the natural and synthetic components. The MX-100 formulation is still the best performing.
4. Our Gen22 experiment is another stress test assaying more substances and combinations based on Gen21. MX-100 and the other best performing combinations are to be tested using the transgenic AD fly model.

Winter Quarter

1. We collected the remaining O flies (“RO”) from the Rose lab at UCI, and Genescient now houses ALL O flies.
2. In our Gen9 experiment, we tested MX-100 again. This time, we included a cohort of flies that didn’t get the treatment until mid-life. The reasoning behind this was to simulate what it might look like if someone in their 50’s started taking MX-100, as opposed to someone that started from youth, which has been the standard model of our fly experiments.
3. MX-100 extended lifespan in all treatment groups by about 50%, including the delayed treatment group.

Spring Quarter

1. To check for normal reproductive function in the flies, we performed a fecundity assay with MX-100 treated flies. No negative fecundity effects were observed, and female egg production was normal.
2. Genescient has decided to shift the focus of our research from cardiology and septic shock to Alzheimer’s Disease (AD).
3. We will use a crawling assay developed by Linda Partridge at University College London using a transgenic AD fly model to screen substances that attenuates the impaired movement of the flies.
4. We will start testing MX-100 and other neuro-protective supplements on these transgenic AD flies.

Summer Quarter

1. In the Genescient Lab, we developed a technique for rapid substance screening using starvation as a means of inducing stress in the flies.
2. This new assay will help us screen substances that help the flies mitigate this stress and live longer, but on a shorter time scale.
3. Our Gen10 experiment uses this new technique, and tests MX-100, as well as 3 reportedly neuro-protective substances: horny goat weed, milk thistle, and PQQ.
4. In this first stress test, we starved the flies using only agar treated with substances. The flies died off within a week, but MX-100 was the most “protective” followed by PQQ.
5. We decided to use MX-100 and PQQ in the next experiment, but using 10% and 20% of normal banana food treated with substances, rather than starving the flies outright.
6. Our Gen11 stress experiment shows that 10% of food is the optimal amount that still shows enough separation in survivorship trajectories, and also mirrors “normal” trajectories, but on a shorter (faster) scale.
7. MX-100 and PQQ performed about equally in Gen11.
8. aOur Gen12 experiment used the stress assay with B and O flies, testing MX-100, PQQ, alone and in combination.
9. During this Gen12, there was an extreme heat wave, and we didn’t yet have incubators in the lab. The heat added another element of stress and caused more rapid deaths, especially for the B flies. We were able to observe some stress resistance provided by the supplements, especially the combination of MX-100 and PQQ.
10. Our Gen13 experiment used the stress test to assay varying doses of Rebuilder and Milk Thistle.
11. Another heat wave was experienced during Gen13, but it appeared that the low dose of MX-100 and medium dose of Milk Thistle were most effective at maintaining survival.
12. Our Gen14 experiment used the stress test to assay Milk Thistle and PQQ alone and in combination.
13. PQQ alone, and combined with Milk Thistle, gave the best stress resistance in Gen14.
14. Our Gen15 experiment was our first large-scale stress test, assaying 13 different substances, including 2 forms of MX-100.
15. The most successful substances in the Gen15 experiment were MX-100a, selenium, low dose Genistein, and lithium.
16. In September, we moved to new lab location in Huntington Beach. We also purchased incubators for flies to help with temperature control during experiments.

Fall Quarter

1. Discussions began about ordering transgenic flies with 9 genes of interest, as well as AD genes.
2. Ben Goertzel submitted his report on the genetic analysis of O and B flies, distinguishing different genes that contribute to “O-ness.”
3. We begin to work with John Tower at USC about AD flies and experimental design ideas such as the crawl tests.
4. Our Gen16 experiment uses the stress test to assay MX-100a, varying doses of lithium, and silymarin. MX-100a + 5mg lithium was the most successful for stress resistance.
5. Our Gen17 experiment uses the stress test to assay MX-100a, BioPQQ, Genestein, Trentinoin, Coumarin in varying doses and combinations. MX-100a was still the most successful.