SPV MEMO

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Transcript #

Hi, this is RJ Tevonian, co-founder and chief science officer of Aion Biosciences. At Aion, our goal is to bring aging under complete biomedical control. We think the way we will achieve this during our lifetimes is by reading and writing to bioelectricity.

Bioelectricity is an emerging field where people look at the electricity in the body. This manifests as voltage across cell membranes.

By looking at this biophysical readout and modulating it with simple methods like chemicals or salts, researchers have been able to achive remarkable outcomes.

Michael Levin has created cancer cells and reversed them to a healthy state with no genetic changes. He has made eyes appear in developmental stages in places where they shouldn’t by altering the voltage of a few cells. He has created two-headed worms.

Clarence Cone has been able to stop cells from dividing and make cells that don’t divide like neurons, just by changing the voltage.

This is an extremely powerful tool that is available in every organ system in the body. However, it has not been effectively applied to aging.

The real challenge is that patterning across the body is not uniform, so if you give somebody a drug that distributes across the whole body, it just doesn’t work because it might stop the heart while trying to change the voltage of liver cells. To address this, we are taking the tools of neuroscience which have been able to remotely read and write to neurons and are applying that to the rest of the cells in the body.

Every cell behaves like a neuron, but just on a longer timescale. On the left are skin cells that are depolarizing over 16 hours and on the right are neurons that are depolarizing over minutes. At Aion, are going to read these non-neuronal cells as quickly as neurons and write to them using closed-loop feedback with a machine that bypasses problems from drugs and pharmacokinetic where we can target individual organ systems outside the brain such as liver, kidney, and thymus.

We believe this can solve aging, given the outcomes from controlled drug experiments in dishes where we can control every aspect of cell fate. We believe we can reprogram cells to younger states using bioelectricity.

To do this we have developed a suite of technology of both read and write methods to monitor and modulate bioelectricity in real time and eventually do this in vivo.

One of the first things I am showing here is a genetically encoded voltage indicator, this is just an example of a marker we can view under a microscope that gives us real-time cell bioelectric data without invasively poking them with electrodes. We have developed imaging suites where we can segment cells and track on an individual cell level the bioelectric waveforms over time to verify that the interventions we are applying are doing what we want.

However these optical methods will not be useful in vivo because they are not amenable to deep tissue imaging.

To tackle that problem we use a custom MRI to image and write to cells in the same dish at the same time. This doesn’t seem directly related to bioelectricity on the surface however, if you look into the history of the MRI, the creator Raymond Damadian created it to image bioelectricity. He noticed that in cancer cells, cancer had a collapsed bioelectric state and that this could be imaged with NMR, later MRI, by looking at water dynamic differences between cancer cells and healthy cells which is correlated with bioelectricity.

We are taking our optical methods and correlating with these MRI observables so that we can translate all of our findings on the microscope to deep tissue.

We correlate optical methods with MRI observables to translate microscope findings to deep tissue. We have developed many different read methods in microscopy, MRI, and electrophysiology in general in our lab. We are ready to look at the complete suite of biophysical readouts that can get us closer to our goal.

We have also developed write methods which include a custom three-axis microscope magnet and benchtop MRI write coil. We look at the cells under MRI and microscope and apply magnetic fields in real time, looking at the functional readouts to detect the correct space of field parameters that will allow us to apply our work in animals.

We explore broad parameter spaces with alot of different tooling, however, we have narrowed in on the idea that everything needs to be usable in sub-centimeter voxels in deep tissue. What this means is that essentially we can just use accoustic fields and magnetic fields which both penetrate very well in the body and spatially encode information.

With all that in mind, we need to do as well as drugs are doing in the dish but with fields so that we have spatiotemporal control as effective as any drug you can take. We use state-of-the-art in drugs and dishes as controls, and we have with yamanaka factors to make stem cells and we are doing this with fields now and not any Yamanaka factors to develop stem cells without touching them so that this can actually be used in deep tissue in the body.

We have done this for both reprogramming for aging and stem cell applications and we have also done this with cancer applications where we have looked at other biophysical readouts correlated with bioelectricity and MRI observables such as water structure where we can use drug to convert the biophysical state of a cancer cell back to a healthy cell, and now we’re just doing that with fields.

We have a solid team here, we have Benjamin Anderson, our CEO; me, the chief science officer; 2 scientists and a founding engineer, all of us wear multiple hats and are super adaptable.

We aim to solve aging but need a beachhead market. The first thing we’re going after is thymus regeneration because the market is large. There is an $80B TAM for just patient who have thier immune system compromised after chemotherapy and their thymus is essentially shrunked.

We believe we can regrow the thymus using external fields. Essentially anything we can do to cell fates can help the thymus. If we can make cells differentiate, dedifferentiate or grow, this can be used for the thymus.

This is also attractive for longevity because everyone after age 30 starts to experience immunosenescence, the thymus shrinks and start to experience all the issues which come with inflammaging.

We want to build this into a giant company that puts a medbed in every home. We believe we can get there.

That’s Aion.