Treatment of Aging Related Diseases – TORC1

Dr. Joan Mannick, Co-Founder, Chief Medical Officer of resTORbio, a clinical-stage biopharmaceutical company focused on the development and commercialization of novel therapeutics for the treatment of aging-related diseases, discusses their lead program that is selectively targeting TORC1, an evolutionarily conserved pathway that contributes to the decline in function of multiple organ systems, including the immune, cardiovascular and central nervous systems.

Dr. Mannick is Co-Founder and Chief Medical Officer of resTORbio. Prior to joining resTORbio, Dr. Mannick was Executive Director in the New Indications Discovery Unit of the Novartis Institutes of Biomedical Research where she led the clinical program that targets fundamental pathways regulating the rate of aging as a new approach to treating aging-related diseases. Prior to joining Novartis in 2010, Dr. Mannick was a Medical Director at Genzyme working in multiple therapeutic areas and a faculty member at Harvard Medical School and University of Massachusetts Medical School. Her NIH-sponsored laboratory focused on the role of protein S-nitrosylation in physiology and pathophysiology. Dr. Mannick received her A.B. from Harvard College and her M.D. from Harvard Medical School. She completed her residency in Internal Medicine at Brigham and Women’s Hospital and an Infectious Disease fellowship as part of the Harvard Combined Infectious Disease Program.

Transcript

Neal Howard: Welcome to Health Professional Radio. I’m your host Neal Howard, thank you for

joining us. We’re going to have a conversation with Dr. Joan Mannick, she’s co-founder, chief medical officer of resTORbio. Now resTORbio is a clinical stage biopharmaceutical company focused on the development and commercialization of some novel therapeutics for the treatment of age-related diseases and she’s joining us today to talk about their lead program and TORC1 and I’m not familiar with that but I’m going to let Dr. Mannick explain all of it to us. Welcome to the program Doctor.

Dr. Joan Mannick:  Thanks very much Neal for having me on your show.

Neal: Glad that you take the time. Give our listeners a bit of background about yourself as co-founder and chief medical officer at resTORbio.

Dr Mannick: Sure. I started a career in academic medicine the trade in infectious disease and ran a basic science lab. Most of the time was at Harvard Medical School but then some of it was also at the University of Massachusetts Medical School and eventually ended up in this biopharmaceutical area and in particular, I ran a program at Novartis where we were targeting fundamental biologic pathways that underlie why we age as a new way to treat aging related diseases. And the lead program would spun out into its own separate company and that is resTORbio and I moved to resTORbio.

Neal: So what exactly is resTORbio involved in that differs greatly from what you were involved in at Novartis?

Dr Mannick: We use sort of most advanced program where we are targeting in human, fundamental biology of aging as a new way to treat aging and other diseases.

Neal: So researching why we age in order to slow down the aging process, stop the aging process? What exactly was the goal here?

Dr Mannick: It’s a great question. So we all have assumed that we just sort of fall apart as we age and it’s inevitable and it’s due to random wear and tear. There’s increasing scientific data that aging is just biology and this biology, there’s a few key mechanisms that contribute to why we age and why our organs … and it’s been shown that if you target this biology, you can keep the function of aging organ systems healthier and you can prevent and treat age-related diseases. So that at least complete … species that the organisms live longer and healthier and so resTORbio is seeing “Does the same biology happen in humans so that we can target these fundamental processes as a new way of treating or preventing aging related diseases in humans?”

Neal: And does this occur in humans you’ve discovered that it does and no how are you dealing with the discovery?

Dr Mannick: Yes. In validated pathway in preclinical species TORC1. TORC1 is a protein complex and … it’s the main … that is activated when we’d and it stimulates cell growth and it stimulates our ability to make proteins and let so we need the activity of this protein when we’re growing and reproducing. But the scientific, many many papers now are suggesting we need less of this protein activity as we age because when you turn down the activity of this protein complex, it stimulates repair pathways and these repair pathways are very important as we get older. So turning down the activity of this complex has a health benefit as we age and this is our lead program – is targeting this protein complex and inhibiting it and we do it for … the function of multiple organ systems gets better in aging organisms. The function of neurologic system … the vascular system improve. We started by just looking at this immune system because it was something we could look at in a short period of time in clinical trials and our data to date suggests that if you inhibit TORC1 in humans in elderly humans, the function of the immune system gets better and they have fewer infections.

Neal: Now inhibiting TORC1, one you say this enzyme is activated not only when we eat but I guess during the digestion process. I mean it’s not something that happens simply because we put something in our mouth, is that what’s going on?

Dr Mannick: What happens is when you eat and you breakdown foods in particular, that stimulate those amino acids in the blood will stimulate the activity of this protein complex. And what’s interesting is when the activity of TORC1 is inhibited and that’s probably some of the benefits of why intermittent fasting is good for our health. We’re turning down intermittently the activity of this protein complex and that allows repair pathways to be activated so normally TORC1 it goes it’s activated when we eat and inhibited when we fast. What happens as we age is this TORC1 complex stops responding to fasting and it stays on all the time. So not only do we need less of it as we get older, we actually end up with more of this protein activity and it’s it stops shutting down in response to fasting so we never have the opportunity to up regulate these repair pathways. So our compound intermittently, in the way we’re dosing it for improving … function, turns down the activity of TORC1 the way it should turn down intermittently in the  way it does in younger adults and what were shown is if elderly people take this, our TORC1 inhibitor once a day and we dose it right now for immune function just on winter cold and flu season, we can significantly decrease respiratory tract infections that the elderly get during winter or flu season and it looks the data suggests this is because their immune function is working better in fighting all sorts of different viruses better.

Neal: Making nature better because as we get older, we lose a bit of our desire to eat like we did when we were younger, we’re less active, we have less to eat and his TORC1 is still on, it’s still highly activated I guess that is what accelerates the dying process.

Dr Mannick: Yes, it’s our bodies get out of tune. We have to re-tune them back to how it is normally functioning and one of the things that seems to get out of tune is this TORC1 activity and we have to tune it back down to younger levels so that our body starts functioning again at a young, healthy way.

Neal: What can we do in our 20s, 30s, 40s and even 50s in order to prepare for this TORC1 decline, We have a quality of life that equals those better functioning organs?

Dr Mannick: What’s nice is when were younger or talk one activity functions normally and the normal function again is that when we eat, it’s activated and when we fast, it turns down. This would suggest the best thing to do when you’re younger is to have some periods of the day where you’re not eating and that’s that intermittent fasting like in a 12 hours day and not eating for another 12. The exact number of hours where you should be fasting, if it’s from 7:00 at night or 7:00 in the morning … but there certainly should be periods of the day where we just stop eating to let TORC1 go down, that is what current scientific data suggests. As we get older, that’s not going to work anymore, at least in some organ systems that they can’t turn the activity down with fasting and that’s when I think the TORC1 inhibitors are going to be beneficial as we get to ages which is probably 65 and above.

Neal: If we’re eating those three square meals a day like we were told you know throughout the 50, 60, 70s and beyond and now we’re told … that we’re consuming all of the processed foods, a serious regimen of fasting would be recommended for everyone. Maybe one meal a day, maybe one meal every other day, who knows.

Dr Mannick: … I think if you just eat for 12 hours a day, three meals at 7:00 in the morning, at noon, at 7:00 at night I mentioned stop eating and snacking. Just stop – looks like it has health benefits. That’s going from eight o’clock at night to eight o’clock in the morning around, that 12 hour period should be beneficial. There is data that that has health benefits and the health benefits may be as good as much more rigorous fasting and much less painful.

Neal: Great, painless is good. Where can we get more information about your company?

Dr Mannick: Yes, we have a website that if you google ‘resTORbio,’ click on our website and it has more information.

Neal: restorbio.com. Dr. Joan Mannick it’s been a pleasure thank you for joining us here on Health Professional Radio today.

Dr Mannick: Thank you Neal, it’s been a pleasure talking to you.

Neal: You’ve been listening to Health Professional Radio and I’m your host Neal Howard. transcripts and audio of this show are available at hpr.fm and healthprofessionalradio.com.au

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