It sounds like something out of science fiction. Someone needs a new kidney, liver or pancreas, but instead of acquiring the relevant tissue from a donor, the body part needed is grown in a lab, and then transplanted into the patient’s body without complication.
The concept of “organ banks” is becoming closer to reality, driven by the science of regenerative medicine which has made major advances in the past decade, in turn enabled by breakthroughs in stem cell biology. An Australian regenerative medicine company is part of this growing revolution by developing an exciting new technology in stem cell-based therapeutics.
The future is now
While the above scenario may seem far-fetched, it’s coming.
Melbourne-based biotech company Cynata Therapeutics is making inroads to bring the future forward at lightning speed. with a particular type of cell medicine—mesenchymal stem cell (MSC).
Partnering with Japanese multinational giant Fujifilm, Cynata has developed a potentially world-changing product. Its solution is currently the subject of a world-first clinical trial in Australia and the United Kingdom. And scientists—and governments—faced with ageing populations, are watching this little Aussie biotech’s clinical trial with keen interest.
Cynata’s first MSC product is called CYP-001, and it is hoped it will be the heavy artillery in medicine’s war against a rare, devastating and often fatal condition: graft-versus-host disease (GVHD).
Unlike a heart or kidney transplant, when a patient’s immune system may reject the transplanted organ as ‘foreign’, GVHD occurs when newly transplanted bone marrow turns on its host.
The body’s defences turning on itself
Bone marrow is the soft, fatty tissue in the cavities of your bones which produces blood cells and platelets, including white blood cells. These are considered the ‘army’ of the immune system, which identify any foreign matter as a threat and seek to destroy it. Bone marrow transplant procedures are often undertaken in cancer patients whose own bone marrow has been destroyed as an unwanted side effect of the treatment of their underlying cancer. Without a functional bone marrow, and therefore in turn a functional immune system, the patient would succumb very quickly to the types infections that normally would not affect us.
“But the immune cells in the donor bone marrow are very smart,” Cynata CEO Dr Ross Macdonald says. “After a transplant, unless they are a very close or perfect match with the patient, they know they’re in a foreign body, surrounded by foreign tissue”
If the white immune cells from the donor marrow go on the attack, GVHD may occur. The condition carries risk of severe health effects, and can damage major organs, including the lungs and liver.
Current treatments include steroids, which suppress the graft immune system’s overreaction, but this requires a fine balance to prevent suppressing the new immune cells too far which could leave patients back at square one.
While there are approximately 25,000 GVHD cases reported worldwide annually, if CYP-001 works, this treatment—and the science behind it—has the potential for far wider applications. The potential applications for Cynata’s technology includes more prevalent conditions like asthma, heart disease and stroke. Cynata is actively investigating the use of their technology in these and several other areas.
“CYP-001 in GVHD is like a policeman at a riot,” Macdonald explains. “The ‘riot’ is the reaction being had in the patient, caused by the donor bone marrow.
“CYP-001 is the cop or fireman who comes in and calms down the rioters, saying, ‘Nothing to see here, everyone calm down and go home’. It’s like an anti-inflammatory cream you might put on itchy and inflamed skin: it allows the body to repair itself.”
The technology behind CYP-001 takes advantage of a recent scientific discovery, the ability to reprogram mature human cells (skin cells or lymphocytes, for example) to an embryonic-like pluripotent state. Such pluripotent cells, called induced pluripotent stem cells (iPSCs), have the capacity for essentially limitless self-renewal and are able to develop into any other type of human cell. This enables all the future requirements for CYP-001 to be met through a single blood donation from a single donor.
Human iPSCs were first described in 1998 by Professor James Thomson at the renowned University of Wisconsin-Madison. Professor Thomson and his colleague and Cynata Co-Founder Professor Igor Slukvin are the inventors behind Cynata’s technology, which draws on this capacity of iPSCs as the starting material to create a consistent and reproducible finished therapeutic mesenchymal stem cell (MSC) product.
Because MSCs do not express the particular markers that identify our own tissues from donor derived tissues, cell therapy with MSCs does not require donor matching, allowing for an “off the shelf” product.
Looking to Japan
“Japan has one of the oldest populations in the world, so the Japanese interest in regenerative medicine is very strong,” Macdonald says. “They understand you can reduce these ballooning healthcare costs substantially if chronic, degenerative and age-related conditions like heart disease, osteoarthritis and Parkinson’s can be stopped in their tracks.”
Japanese multinational Fujifilm may be known historically as a photographic products company, but in more recent years they have become renowned for their growing business in healthcare, particularly regenerative medicine.
“Fujifilm have their own research and development departments but like many big pharmaceutical companies, [they] look to smaller, innovative, agile companies to find new technologies,” Macdonald explains. “We don’t plan to develop our own tech fully for every potential application as the cost is incredibly high, so our relationship with Fujifilm is strategically important for us.”
In 2015, Fujifilm acquired Cellular Dynamics International, a biotech company founded by Thomson in 2004 and the ‘sister’ company of Cynata. Cynata approached Fujifilm and, in January 2017, Fujifilm purchased a 9 per cent stake in Cynata, along with the option to take an exclusive licence to manufacture and market CYP-001 worldwide. Under the agreement, Fujifilm will pay Cynata up to an additional $60m, plus royalties on product sales, as well as fund the further development of CYP-001.
“In Fujifilm, Cynata now has a company with global resources in healthcare which can quickly and effectively develop technology and bring it to clinical trial and to market,” Macdonald says. “This technology will reach people. That is the most important thing.”