Strangers in a strange land

Picture it: a spaceship lands on Earth, opens, and an alien steps out. The alien has a mission – to assimilate and fit in anywhere he goes (US, Russia, China), immediately. Eat what we eat, speak our language, become part of a human family, instantly. No learning curve, no practicing, no time to acclimate to his surroundings. Become human or die. His surviving chances are slim to none.

While this story is science fiction, it’s how Gong Chen, founder of NeuExcell, explains a very real process by which some researchers are attempting to use external stem cell injections to repair brain damage, and why he believes it’s the wrong approach.

“The stem cells are strangers in a strange land after being injected into an adult mammalian brain,” he says. He points a finger at me. “It’s like asking you to get on a plane this afternoon and land in China and instantly speak Mandarin fluently, instantly make a home and family and friends, and launch a successful career. It’s not realistic.”

“Let’s take a really low number,” Chen goes on. “Let’s say that 5% of one patient brain has been affected by Alzheimer’s. That’s four billion neurons. Using the high limit of a 10% survival rate for stem cells (remember the alien who probably won’t make it) and we are at 40 billion cells that would need to be injected – about half of total the neuronal cells in the brain. Let’s do the math and really think it through quantitatively… it’s just not realistic.” 

Neighbor (cells) helping neighbor (cells)

So, forget about our alien friend from outer space. Now, simply picture that a local person steps up to fill the vacant position instead. They’ve always lived there together, already speak the same language, and already have a support system of family and friends. They even have connections in ancestral lineages. Asking a neighbor to help is far more convenient than asking for help from a Martian.

This is the model NeuExcell is using to repair damaged brains. Gong Chen explains why it offers a better chance of success.

Every neuron in our brain is surrounded by a group of supporting cells called glial cells. When a person suffers from neurodegenerative disease like ALS or Alzheimer’s, or suffers a neural injury like stroke, neurons are injured or die. While neurons cannot replicate themselves, their neighboring glial cells can.

As soon as a neuron dies or is damaged, the neighboring glial cell become reactive and proliferate by replicating itself to fill in the gap. NeuExcell is working on a new technology that converts these reactive glial cells into functional neurons.

When a person leaves his job, for example, rather than introducing someone who has never worked in that field, the position is filled by someone with experience at a neighboring desk. “We aren’t introducing aliens,” Chen says. “We are using neighbors and friends to fill in for the damaged neurons.”

The power to heal has potential to disrupt the healthcare landscape

To say that this technology has the potential to change the world is not an exaggeration. Imagine slowing the progress of Alzheimer’s, returning mobility to stroke victims, and restoring quality of life to someone who has suffered a concussion brain injury. It’s big.

Neurological disorders such as stroke, Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, Amyotrophic Lateral Sclerosis (ALS), and spinal cord injuries have inflicted millions of patients in U.S. and even more worldwide. In fact, stroke is the leading cause of long-term disability in U.S., with nearly 800,000 people experiencing a stroke each year, and totaling 7 million stroke survivors. Alzheimer’s disease now affects 5.7 million patients in U.S. and the number is growing.

The medical and financial burdens are extraordinary, not only to the families, but also to the society – the annual cost to care for Alzheimer’s patients in America is projected to be over one trillion dollars by 2050.

Finding and funding success

In 2010, Penn State Professor and Verne M. Willaman Chair in Life Sciences Dr. Gong Chen and his team started working on in vivo neuroregeneration. Research moved quickly, and by 2012, they had filed the first patent for the technology, and obtained the issued patent on NeuroD1 in 2017 by USPTO.

They published their first paper on in vivo conversion of glial cells into functional neurons in mouse model with Alzheimer’s disease in the end of 2013. The success attracted a lot of media attention and exposure in many scientific journals. Recently, their further work on stroke brain repair has been accepted for publication in the journal of Molecule Therapy.

In their documentation, they were able to show 90% conversion efficiency, the highest in the world. Even better than that conversion rate is the fact that glial cells can divide and replace themselves, providing an endless reservoir that can never be depleted. In preclinical studies, Chen’s team has demonstrated success in a stroke model where up to 80% of ischemic injured neural tissue was repaired and motor function and cognitive deficits significantly rescued.

In 2015, the Skip Smith family made a donation of $5 million dollars, making a huge impact on the study. After the Smith’s donation, angel fund money was invested into the company, providing them with the money to establish its own lab and office space independent of the university lab. They made the move to Innovation Park’s Technology Center Incubator. “It’s very convenient to have the company so close to my office at Penn State,” Chen says.

NeuExcell is a testament to President Barron’s commitment to entrepreneurship to have this resource available within the Penn State family. “He is very supportive and encouraging of faculty to start companies,” Chen says. “It’s very important that professors don’t just do mechanistic research, but that they actually also DO the translational work.”

New space, new talent, major progress

Since 2015, with limited angel investment resources, the company has been moving forward, and recently that pace has dramatically accelerated. Just this summer, NeuExcell added Executive Board Chair and Acting CEO Peter Tombros. Tombros helped build Pfizer’s pharmaceutical business from 1968 to 1994, served for eight years as CEO of Enzon, then as CEO and Chairman of the Board of VivoQuest, a private start-up drug discovery company, until 2005. A Penn State alumnus, he has had long-time involvement with Penn State’s Eberly College of Science and Hershey Medical Center. In 2006, Peter was selected for Penn State’s highest honor, the Distinguished Alumnus Award.

Joining Tombros on the board is Amsterdam Molecular Therapeutics (AMT) founding CEO Ronald Lorijn. Lorijn’s company AMT was responsible for bringing Glybera, the first recognized gene therapy product in the world, to the global market.

Chen notes that the transition from lab work to a therapy is a long journey. Once a company is running and has licensed a patent through Penn State, Penn State employees are not allowed to use Penn State resources to benefit the company in the most practical and scientifically efficient manner due to federal regulations. Instead, Dr. Chen has been instructed to use outside labs for testing and verification, at much higher costs. “I do wish it were more synergistic, and I hope over time we improve the interactions between the university and the spinoff companies to facilitate the technology translation.” Chen says.

Right now, a research lab of 40 people is conducting tests on mice here in Happy Valley, and a lab in China is conducting translational research in primates. The primate research, Chen says, is critically important, explaining that “a monkey brain is much bigger than a mouse brain. It’s closer to a human brain. We’ll never inject a human brain until we have big success in primates.”

The road to the marketplace

For the next two years, the company is in advanced R&D stage, which will entail investigational new drug (IND) enabling studies. After that time, they anticipate two years in Phase One, which will allow for FDA-approved human clinical trials. Once they can document positive effect in human clinical trials, it’s on to Phase II and Phase III, and then
the marketplace.

While they are testing in vivo direct reprogramming of glial cells into neurons using AAV-based gene therapy, they are also testing an oral drug that would target widespread neuron loss, and are also working on a drug that would effectively treat neonatal epilepsy.

The big goal? NeuExcell wants to bring hope to millions of patients by transforming billions of glial cells into neurons to treat stroke, Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and many more.

Game-Changing Donation Illustrates Philanthropic Trend in Medical Research

If you compare Gong Chen’s research into treatments for brain trauma patients to a smoldering campfire, then Charles “Skip” Smith’s $5 million donation was a jolt of kerosene. In 2015, Chen benefited from a growing trend in scientific research—private contributions. A 1948 Penn State alumnus, Smith was motivated to help Chen propel his research
and shorten the timeline for developing a treatment for neurogenerative diseases like Alzheimer’s to within ten years. In turn, Chen was able to license more advanced intellectual property into a start-up company, NeuExcell, to pursue commercialization.

The company has lab space in the Technology Center business incubator at Innovation Park. In 2015, the Chronicle of Philanthropy reported that private philanthropy was beginning to fill gaps left by stagnant or declining federal funding for scientific research. Although not a replacement for federal dollars, private funds offer researchers certain advantages:

Like Smith’s gift to Chen, a large infusion of cash can jump-start a project that may have been chugging along and significantly increase its pace.

Private donations also make it easier for researchers to conduct work internationally, while federal grants would bring restrictive limitations for researching overseas. Part of Smith’s gift helped Chen advance his research in China.

Most public funding has limitations. Private donations allow for a broader use of funds that compliment public funding.

Overall, philanthropic support for research leans heavily toward the medical field and, like Smith’s donation, is typically aimed at developing treatments or cures at a more rapid pace. Donors are often motivated by a personal experience with a specific medical condition, like MBI-Founder Ted Stanley who contributed $650 million to the Broad Institute to fund research into the connections between genetics and severe mental illness. Stanley said his gift was driven by watching his son, Jonathan, suffer from bipolar disorder.