Dr. Fossati’s Work Opens a Window into MS

Dr. Valentina Fossati conducts research in The New York Stem Cell Foundation Laboratory to unlock the mysteries of multiple sclerosis (MS), a disease that affects over 2.5 million people worldwide.

Following her doctoral studies, Dr. Fossati's fight against MS became personal. She was diagnosed with the disease in 2008 when, as she puts it, "I woke up one morning and my leg didn't wake up with me."

As both a scientific expert and, now, a patient, her diagnosis has only strengthened her resolve to strive to find treatments to this intractable, mysterious disease.

MS is a demyelinating disease of the brain and the spinal chord, meaning that the disease causes damage to the myelin sheath, or the protective covering that surrounds nerve cells. When this protective sheath is damaged, nerve signals slow down or stop. As a result, MS patients have difficulty with movement as well as other symptoms.

What exactly causes MS is unknown. The most common thought is that autoimmunity, a virus or genetic predisposition, leads to this disease. Environmental factors also play a role.

In a healthy brain, cells called oligodendrocytes help the nerve cells carry electrical signals to other parts of the brain and body to control movement, heartbeat, breathing, and other physical impulses. In MS patients, oligodendrocytes and eventually nerve fibers are damaged, failing to conduct these electrical signals properly, which can lead to severe physical and even cognitive disabilities. There is no known cure to the disease.

"The best way to study MS and test possible new treatments is with live, human diseased brain cells," says Dr. Fossati. "Studies in animals really don't translate to humans, because animals aren't known to get MS naturally. The difficulty of studying MS in humans is that you can't remove diseased brain cells from someone who is still living, and brain cells from someone who has died aren't as viable for research."

So Dr. Fossati is doing the next best thing – creating a live, human model of the disease in the laboratory. Thanks to a collaboration with Dr. Saud Sadiq and the Tisch MS Research Center of New York, MS patients have been recruited to donate skin cells. These cells are thereafter reprogrammed to create induced pluripotent stem (iPS) cells, capable of becoming every cell type in the body. Through a process known as differentiation, Dr. Fossati's team manipulates the cells to become neural (brain) cells that have MS.

"By creating a model of oligodendrocytes and neurons using stem cells and then reproducing the stressors of the disease, I hope to create a window into the brain to observe and to better understand how, in MS, the oligodendrocyctes, the myelin sheaths, and the nerve fibers get damaged and how we can fix or prevent that. My ultimate goal is to find more effective treatments to stop and reverse the damage of this disease."

Dr. Fossati's interest in the promise of stem cells brought her to the U.S. after she received her PhD in Italy, where regulations would have made her work with embryonic stem cells (hESCs) difficult. After post-doctoral work at Mount Sinai School of Medicine, Dr. Fossati received the NYSCF – Druckenmiller Fellowship to initiate her work with The New York Stem Cell Foundation, where she has conducted her research since 2009. She is currently a NYSCF-Helmsley Investigator.