A Profile of Tissue Engineering Efforts at LyGenesis

LyGenesis is the company founded to develop the technique of implanting organoid tissue into lymph nodes in order to allow it to survive and grow in the body. Some organs can carry out much or all of their function more or less regardless of location in the body, such as the liver and thymus. Thus any viable transplant strategy that leads to functional tissue thriving in the body should help patients. LyGenesis is initially focused on restoring liver function via this approach, but the thymus is next in line, with an eye to reversing some of the age-related decline in immune function.

Let's spend a little bit of time talking about your therapy. Let's say I hop into a time machine and go to the future, to whatever time it may be for it to have fully hit the market. What's your procedure going to look like?

So let's start with the present. Today, when a person needs a new liver, then a major transplantation surgery is their last option. This is an expensive and major operation - if you ever search online for "liver transplantation," you really do want to brace yourself. And then there's our approach, which uses endoscopic ultrasound to engraft cells into a patient's lymph nodes, and transforms the transplantation process into an outpatient procedure. That's one of the fundamental value propositions of our technology. The patient would be put under light sedation, the endoscope would be moved into a place where it can access your lymph nodes - the mesentery, in your abdominal region - and thirty minutes later you'd have multiple ectopic cell clusters placed there, engrafted by a cellular therapy, and you'd potentially even be able to leave the same day. Over the course of the next few weeks and months your lymph nodes would serve as bioreactors to grow multiple ectopic organs - a process called 'organogenesis' - that would begin filtering your blood and providing life-saving support. That's our vision of the future for our lead candidate in liver regeneration.

So the question that follows from that is: is this a therapy that would be a final procedure? Or is it a stopgap for those who are waiting on a transplant list for a full replacement?

One group of patients, for whom we hope this will be a single procedure and a curative therapy, are the many people with end stage liver disease. Those who have gradually and progressively lost liver function over time. Right now, once you get to a certain threshold where you've lost enough liver function, if you're healthy enough (and don't have any contraindicated medical comorbidities) you might make it onto the liver transplant list. Once you've made it on there you'll wait, oftentimes hundreds of days, or even longer, to receive an organ. And that's if you're lucky. So there's a huge unmet need. Patients need a new liver, but they're too ill and that prevents them from being eligible for a full organ transplantation. Right now there's no viable therapy for these people. So we think our therapy will be the first in line therapy for those patients.

How many lymph nodes, on average, would you need to use for this to work? Are there going to be any side effects from this process?

Right now, our best guess is that we will be grafting ectopic livers into, probably, three to five lymph nodes. You spread the mass of the ectopic organs across multiple lymph nodes, not just a single lymph node. That's our best guess and clinical development plan right now. In the research we've been doing for almost decade now, we've tried everything from a single lymph node to twenty lymph nodes or more, in the different animal models. And we've seen no adverse effects in terms of the transition from the lymph node to an ectopic organ. One thing we stress is that when you look at what happens over time, the lymph node disappears. The lymph node acts like a bioreactor in this process - once it's kicked the organ growth into gear, the organ takes over and the lymph node disappears. And because our bodies have hundreds of lymph nodes distributed throughout, we don't expect that losing a handful of them will produce any untoward effects.

How could this enhance people's longevity going forward?

Another great regenerative medicine story from our platform is based on our work on the thymus, which is fascinating. So, we have proof-of-concept data showing that we can regenerate the thymus ectopically inside the lymph nodes, as well. The thymus, as you may know, has a complicated biology; it does a lot of different things. But there is some indication that one of the effects of rebooting the thymus is to reboot the immune system - which absolutely could have regenerative, and therefore potential longevity, effects. We have try to be very careful about this, lots of things work in small animals that do not translate to people - there are jokes that the medical field has cured cancer in mice so many times over by now. We have to be careful when talking about longevity. Here's this dream of man since the beginning of time, to live longer. I think with some of the regenerative medicine and our understanding of biology we can start to make some inroads but, for what it's worth, I'm very careful not to promise that we're unlocking the fountain of youth. That's not the case. We're trying to develop science-based, FDA-regulated therapies to address unmet medical needs - even though, admittedly, the famous one would be potential downstream effects on aging and longevity.

Link: https://www.longevity.technology/exclusive-profile-lygenesis-and-growing-ectopic-organs/