Technology of the future: how LyGenesis is aiming for the immortal liver

Longevity Week’s Science Summit ended with a bang – and a mythical vulture.

The last in the series of overviews of the Longevity Forum’s Science Summit at Oxford’s Oriel College, part of Longevity Week and hosted by Professor Lynne Cox and Jim Mellon.

Longevity.Technology: When it comes to organ transplantation, LyGenesis is a disruption titan. But a solid vein of science runs through the company, with a sensible focus on scaffolding their developments with practical research wraparounds, such as vascularisation and business strategies such as scalability and practical routes into clinic. 

After a mind-blowing day of longevity science, the conference ended with a boom from a lecture by Michael Hufford, PhD. Michael is the Co-Founder and CEO of LyGenesis, a clinical stage drug development company whose cell therapies use lymph nodes as bioreactors to grow functioning ectopic organs. An entrepreneur and drug developer, he has over 20 years of experience in the development and regulatory approval of small molecules (Cypress Bioscience), biologics (Amylin Pharmaceuticals, LyGenesis), as well as drug delivery technologies (e-Nicotine Technology).

Michael Hufford, PhD - Co-Founder and CEO of LyGenesis
Michael Hufford, PhD – Co-Founder and CEO of LyGenesis

Dr Hufford’s lecture was titled “Prometheus unbound: From myth to the clinical reality of organ regeneration”, drawing on the parallels between LyGenesis cell therapies and the myth of Prometheus. “Prometheus stole fire from Zeus and gave it to humanity,” explained Hufford. “For his crimes, Prometheus was punished by Zeus, who bound him with chains and sent an eagle to eat at Prometheus’ immortal liver every day, which then grew back every night. This thousands of year’s old myth reflects a fundamental truth – the liver tries to regenerate itself.”

LyGenesis plans to create the immortal liver. For example, one of its main targets is to ensure the supply of liver transplants to those who need it.

“At the moment, the demand for organs far outstrips the supply,” said Hufford. “Twenty to thirty people die every day awaiting transplants in the US. Compounding this challenge is the fact that we discard a huge number of donated organs, approximately 30-40% of livers are donated but not transplanted in the US, so this precious resource is going to waste. There is a supply of livers and the billions of hepatocytes that comprise them, but we can’t use all of it.”

Cost is also an issue. Hufford described the overwhelming costs that are associated with liver transplants: “In the US, the acute costs of a liver transplant are around 800,000 dollars. Further, the sickest patients will not survive the transplant procedure and those that do may need lifetime immune suppression. LyGenesis’s technology aims to reduce the costs and increase the available supply to keep up with demand.”

So how are they going to do this? Hufford said that with just one donated liver LyGenesis can treat up to 75 patients. Not only this, but the cell therapy is engrafted using a minor surgical procedure conducted under light sedation.

“We use an endoscopic ultrasound to engraft cells into a patient’s lymph nodes, which transforms the transplantation process into an outpatient procedure,” Hufford explained. “That’s one of the fundamental value propositions of our technology. Instead of the costly and high-risk organ transplantation procedure that is available today, 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 twenty minutes later you’d have multiple ectopic cell clusters engrafted there, 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, slowly regrowing into functional livers, as LyGenesis has shown is possible in pre-clinical experiments in mice, pigs and dogs.

“Lymph nodes are basically 400 to 500 miniature bioreactors,” said Hufford. “Cancer hijacks lymph nodes to help tumours grow. LyGenesis hijacks them to help develop functional ectopic organs, including liver tissue.”

LyGenesis is getting ready to begin enrollment in a Phase 2a clinical trial for patients with End Stage Liver Disease next month at Harvard’s Massachusetts General Hospital.

“The FDA understood that for organogenesis to occur, the process is critically contingent on the presence of pro-growth factors secreted by the diseased liver,” Hufford said.

“Adjustment of liver size to 100% of what is required for homeostasis has been called the ‘hepatostat’. Removal of a portion of the liver is followed with local regeneration of a limited degree, so there are pro-growth signals that are trying to get native hepatocytes to thrive.

The engraftment of our cell therapy uses these pro-growth signals to support and sustain the growth of the new ectopic livers.”

Looking at the health economics, Hufford stated they could be restoring liver function at a fraction of the current price of a liver transplant.

During the lecture it was also announced that LyGenesis had achieved positive in vitro results of a novel combination drug-biologic product for infants with inborn errors of metabolism, and that it would be adding these orphan pediatric indications to its drug development pipeline. Read more about this here.

More from the Science Summit:

The environment and the exposome in longevity – Professors Sarah Harper and Paul Shiels

Care needs of an aging population – Professor Adam Gordon 

Immune systems and internal clocks in aging – Professors Liz Sapey and Aarti Jagannath