Dr Joan Mannick is one of the world’s leading rapamycin and mTOR researchers in the longevity field. Joan has a background in academic medicine and is currently CEO at her own company Tornado Therapeutics where they focus on developing the next generation of mTOR inhibitors. One of the company goals is to create a mTOR inhibitor which is better than Rapamycin. Throughout the years Joan has made important discoveries in humans when it comes to finding a connection between mTOR inhibition and improvement of the aging immune system. In this podcast we are going to talk about her research, drug development, mTOR, rapamycin, rapalogs and other interesting longevity topics.

00:00 Intro
01:59 Longevity interest and research
03:40 How Joan's longevity career started
06:24 What is mTOR and what makes it unique
08:55 Mechanisms underlying the effects of mTOR
10:56 How translatable is the effects of mTOR to humans
12:43 mTOR inhibition and it's upstream pathways
14:02 What is Rapamycin and how it was discovered
15:21 The weak points of Rapamycin
16:35 mTOR contains of mTORC1 and mTORC2
17:28 What is a rapalog
18:31 Detect early signs of mTORC2 inhibition
19:40 Tornado Therapeutics and it's portfolio of rapalogs
23:13 Joan proposed a courage trial to the board
27:07 Animal data show Rapamycin may improve the immune system
28:09 Designing the dosing protocol for phase 1 trial
29:26 The phase 1 trial and it's results
32:50 Aged immune system may drive aging
35:12 A good immune system may prevent cancer
36:05 Influenza and the aging immune system
38:29 The phase 2a trial and mTOR inhibition in elderly
39:32 The phase 2b and 3 trial
40:28 Antiviral genes are upregulated
42:26 Catalytic mTOR inhibitor RTB101
43:05 The phase 3 trial did not meet the primary endpoint
46:02 Pilot trial to decrease the severity
46:59 Dose protocol of Everolimus and RTB101
49:37 Safety profile between Everolimus and RTB101
52:10 Vaccines and/or mTOR inhibitor
54:51 Dosing protocol to improve the antiviral response
56:44 Taking a break or continue taking mTOR inhibitor during a common cold
57:49 Immune system biomarkers
59:24 Sarcopenia and mTOR inhibition
1:01:50 Leading candidate in Tornado Therapeutics portfolio
1:03:19 Safety profile of the rapalog TOR101
1:06:13 Next step for TOR101
1:08:25 Rhinovirus trial with TOR101
1:08:56 When will a mTOR inhibitor be FDA approved for longevity
1:10:28 Lifespan studies with TOR101
1:11:49 Joan's own personal approach to mTOR inhibitors
1:13:33 Most promising longevity interventions
1:15:30 Autophagy and mTOR inhibitors
1:16:40 Big challenges in the longevity field
1:19:20 What the field really needs
1:20:48 Contact information

Links
- Tornado Therapeutics
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- Joan's LinkedIn
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- Joan’s research publications
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- Big thanks to TimePie for the research help for this episode
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Rapamycin resources
- Rapamycin Longevity Lab
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- Rapamycin.news
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- Rapamycin Facebook group
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- Rapamycin Reddit group
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Connect with Krister on:
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Disclaimer: The podcast is for general information and educational purposes only and is not medical advice for you or others. The use of information and materials linked to the podcast is at the users own risk. Always consult your physician with anything you do regarding your health or medical condition.

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