A scientist and company founder at the Buck Institute for Research on Aging in Novato has developed stem cell lines from patients with Parkinson’s disease that will accelerate research on the motor disorder which results from death of brain cells that generate dopamine, a crucial neurotransmitter. Dopamine controls the human brain’s regulation of movement and emotions, including response to reward and pleasure.
Xianmin Zeng, a faculty member at the Buck Institute, published her findings May 18 in the Public Library of Science. Zeng derived 10 lines of pluripotent stem cells from tissue donated by Parkinson’s patients. These stem cells can differentiate into many human cell types, especially to replace dopamine-producing neurons lost in the disease that affects nearly a million Americans and 7 million people worldwide.
Humans have far more dopamine than most species. High dopamine levels are associated with aggression and competitiveness (business ambition), as well as intense sexual feelings, euphoria and control of impulses. Low dopamine levels are found in people with Parkinson’s, Alzheimer’s, depression, binge eating, drug and gambling addiction, schizophrenia, bipolar disorder and attention-deficit disorder.
Canadian actor Michael J. Fox, who acquired Parkinson’s at age 30 and turns 55 on June 9, poured resources into propelling research into the disease. About 4 percent of people with the disorder develop it before age 50. Parkinson’s disease causes tremors, muscle stiffness, lack of facial expression, speech impairment, and loss of balance and coordination. There is no cure yet, but Zeng’s work holds huge promise.
About six years ago, Zeng founded XCell Science, a Novato-based company that sells nearly 80 products including 20 engineered lines of induced pluripotent stem cells, neural cells, and models to promote gene-editing research on diseases of the central nervous system: Parkinson’s, Alzheimer’s, amyotrophic lateral sclerosis, Huntington’s Disease, schizophrenia and autism.
AVOIDED VENTURE CAPITAL
XCell Science, which has six employees in addition to Zeng, also does gene cloning, toxicity screening, drug testing and contract research. The company is funded with private money, Zeng said in an interview with the Business Journal. She avoided venture capital investors because they usually exert major control over a startup company’s growth and focus. “I was very uncomfortable — if they tell me that another area is hotter,” she said, VC funds could jump to another venture.
“It’s a company based on technology developed in my lab,” Zeng said of XCell. “I just got a small-business-innovation grant” from the National Institutes of Health, awarded on March 1. “That provided $1.5 million.” She brings scientific direction for the company “and business strategy,” as well as “executive decisions,” she said. “I don’t run daily operations. I make sure they have enough business.”
She recruited an executive who worked for a large biotech company to take the reins of XCell at the end of the summer. Zeng won’t disclose his name.
“Eventually my goal is to develop and sell therapy,” Zeng said. “That’s why I spun out the company. It needs to have a commercial entity.” The Buck Institute is an academic institution. XCell was one of the first private companies to emerge there.
LABS AS CUSTOMERS
Hundreds of laboratories in the United States and worldwide study Parkinson’s disease and other diseases of aging, and these laboratories are potential customers for products developed at XCell Science, which has distributors in Europe and Japan. A one-milliliter vial of induced pluripotent stem cells costs an estimated $5,000. Pluripotent stem cells can differentiate into nearly any type of human tissue, including dopamine-producing neurons lost in Parkinson’s.
Scientists start with adult somatic or embryonic stem cells, which can differentiate into cell types including muscle, skin and bone. In adults, stem cells remain quiescent until disease or injury activates them. Stem cells can be cultured to divide and replicate into a stem-cell line of identical stem cells, then stimulated to specialize. Embryonic stem cells can differentiate into more cell types than adult stem cells.
Totipotent: Able to differentiate into all cell types, such as zygotes, formed at egg fertilization and first few divisions thereafter, can produce entire organism.
Pluripotent: Able to differentiate into most cell types, such as embryonic stem cells and those formed in early embryonic cell differentiation.
Multipotent: Able to differentiate into closely related family of cells, such as hematopoietic adult stem cells that become red or white blood cells or platelets.
Oligopotent: Able to differentiate into a few cells, such as adult lymphoid or myeloid stem cells.
Unipotent: Able to reproduce only their own type of cell or to self-renew, such as adult muscle stem cells.
Total estimated cells in human body: 37 trillion (37,000,000,000,000)
Neural stem cells: Differentiate into nerve cells (neurons), astrocytes and oligodendrocytes.
Transdifferentiation: Reprogramming stem cells to produce cell types not of the stem cells’ lineage, such as neural stem cells differentiating into muscle cells.
Induced pluripotent stem cell: Adult cells genetically reprogrammed to resemble embryonic stem cells by being forced to express particular genes or factors. First created in 2007 in humans, useful for drug development, disease modeling and transplantation. Viruses used to introduce reprogramming factors into adult cells.
Countries that distribute XCell Science products
Belgium, Luxembourg and Netherlands: Sanbio
Denmark, Finland, France, Germany, Italy, Norway, Spain and Sweden: tebu-bio
Japan: Veritas Corp.
Commonly mutated genes implicated in Parkinson’s
SNCA, PARK2, LRRK2 and GBA