Researchers can now make brain cells from the skin cells of patients with ALS, also known as Lou Gehrig’s disease, to better study the fatal disease.
The team used a genetic engineering technique to convert patients’ adult skin cells into “induced pluripotent stem cells,” which can then be coaxed into becoming brain cells.
“We make brain cells out of the patient’s own skin,” says Jeffrey Rothstein, professor of neurology, who directs the Brain Science Institute and the Robert Packard Center for ALS Research at Johns Hopkins University.
Lou Gehrig’s disease
ALS (amyotrophic lateral sclerosis) damages and eventually kills nerve cells in the brain and spinal cord. Patients lose voluntary muscle control—affecting movement of arms and legs, speech, swallowing, breathing, or other functions.
They may eventually become totally paralyzed. The ALS Association estimates that about 5,600 people are diagnosed with the disease in the United States each year.
There is no known cure. The only FDA-approved drug, riluzole, may only add a year to a patient’s life.
Since the 1990s, researchers have studied ALS and potential treatments in mice. The mouse model looks very much like what happens in people, Rothstein says, “but after 25 years, it has not led to the development of a drug that works in our patients.”
A handful of drugs were effective in mice but failed in humans.
“There has to be a sea change in how we approach ALS,” Rothstein says.
Because there is no ethical or simple way to obtain brain tissue from living human ALS patients, researchers turned to induced pluripotent stem cells, a technique that gives researchers a tool to look at diseased human brain cells, including specialized nerve cells called astroglia, which play a critical role in ALS progression.
Rothstein and his team have created 22 patient-specific cell lines that include some common mutations associated with ALS. The lines are deposited in a cell library, to be shared with other scientists.
“These human cellular tools will serve as a platform to understand ALS and someday discover new drugs to treat our patients,” says Rothstein, senior author of a study about the work published online in PLOS ONE.
The library includes cells from patients with inherited ALS, which accounts for about 10 percent of cases. The researchers have also generated cells from patients with the noninherited form of the disease, sporadic ALS, which makes up 90 to 95 percent of ALS cases.
A real model
From one patient, the researchers collected a genetic variant found in both inherited and sporadic forms of the disease, and added it to the library.
Scientists from around the world have already used the library, and Rothstein says he hopes it will grow, with researchers making deposits of their own patients’ cell lines.
Eventually, induced pluripotent stem cells may be used to model diseases other than ALS and to test potential drug treatments, Rothstein says. “Now we have a real model for what’s wrong with my patients.”
The National Institutes of Health, Johns Hopkins, the Emerald Foundation, the ALS Association, and the US Defense Department supported the work. The cell lines are freely available to all researchers from a public warehouse maintained by the Coriell Institute.
ALS is known as Lou Gehrig’s disease because the New York Yankee star and baseball Hall of Famer died of the disease in 1941 at age 37.
Source: Johns Hopkins University