Couple give embryos, 'hope' to UM in fight against rare disease

Kim Kozlowski
The Detroit News

Alexandra Cellucci was 28 when she was diagnosed with neurofibromatosis, a rare genetic disease that causes noncancerous tumors to grow on the body's nervous tissues. She was also eight months pregnant at the time, but she would eventually deliver a healthy baby girl.

Neurofibromatosis, known as NF for short, runs in Cellucci's family, so she knew her daughter could have the disease and she could pass it on to future children. So she and her husband, Marc, used reproductive medicine to conceive another baby, had the embryos tested for the gene that causes NF and had doctors implant embryos in her womb without the mutated gene.

Alex Cellucci, 35, rubs fabric on her right eye, where she had a tumor removed the previous day, while watching a movie with her daughter, Maible, 6, at their home in Quincy, Mass. on Tuesday, Aug. 6, 2019. Alex and Maible both have neurofibromatosis, a genetic disorder that causes tumors to form on nerve tissue. Alex was diagnosed with neurofibromatosis type 2 at age 28 and has since endured two MRI scans every year to monitor tumors.

Cellucci, now 35, never got pregnant again, despite many attempts. She and her husband have since learned their daughter Maible, now 6, also carries the gene for NF2, one of the three forms of the disease. The day before Maible's birthday last November, the girl asked if she had the disease. Cellucci said she told her yes and that she would be OK.

That's why the Massachusetts couple donated seven embryos with the NF2 gene to the University of Michigan so researchers could create an embryonic stem cell line that other researchers could study, with the hope of one day discovering a breakthrough. In a perfect world, such a development would come before their daughter endures any symptoms.

Alex Cellucci, 35, poses for a portrait at her home in Quincy, Mass. on Tuesday, Aug. 6, 2019. Alex and her 6-year-old daughter, Maible, both have neurofibromatosis, a genetic disorder that causes tumors to form on nerve tissue.

“I just wanted hope," said Cellucci, who had surgery last month to remove a benign tumor behind her eye. "They could possibly find a cure for (Maible) ... and offer hope for other families."

UM researchers have turned the Celluccis' embryos into the first stem cell line that models NF2, which is one of the more rare forms of the disease. Besides the tumor growth, NF2 comes with a host of issues, including hearing loss, ringing in the ears and loss of balance. Symptoms typically appear in the teen years.

The embryonic stem cell line modeling the disease, created by Professor Gary Smith, director of the MStem Cell Laboratories, has been accepted onto the National Institutes of Health Human Embryonic Stem Cell Registry for other scientists to study and make discoveries around interventions and a possible cure. Another line also is under review.

Alex Cellucci, 35, watches a movie at her home in Quincy, Mass., a day after having a tumor removed from behind her right eye.

Researchers can apply to access the stem cell lines on the federal registry to study how diseases form and develop, with the aim of finding ways to better understand, treat, delay and possibly even cure diseases.

Smith has derived all of UM's 56 embryonic stem cell lines on the national registry, including 36 disease-specific lines. He said the personal stories behind all of those stem cell lines are important.

"We just don't do science to do science," Smith said. "We do science to help others. Here is a family that recognizes that. Sometimes that gets lost on people. ... We really do want to help people."

The NF2 stem cell line comes as neurofibromatosis scientists and clinicians prepare to gather next month for their annual conference in San Francisco.

Alex Cellucci, 35, and her daughter, Maible, 6, watch a movie at their home in Quincy, Mass. on Tuesday, Aug. 6, 2019. Alex and Maible both have neurofibromatosis, a genetic disorder that causes tumors to form on nerve tissue. Alex was diagnosed with neurofibromatosis type 2 at age 28 and has since had two MRI scans done every year to monitor tumors. Most recently, Alex had a tumor removed behind her right eye on Aug. 5, 2019.

It also comes as Detroit businessman and Cleveland Cavaliers owner Dan Gilbert has used philanthropy to support the small research community of neurofibromatosis. His 23-year-old son, Nick, was born with neurofibromatosis type 1

NF2 afflicts 1 in 33,000 people worldwide, while NF1 is more common, occurring in 1 in 3,000 to 4,000 people, according to the National Institutes of Health. NF1 typically begins in childhood and leads to skin changes and bone deformity. Schwannomatosis, the rarest type of NF, causes intense pain. 

Gilbert, who suffered a stroke in late May, has spoken about neurofibromatosis and also about how Nick, a Michigan State University student, had to undergo brain surgery in 2018 to remove tumors.

Gilbert, a billionaire, has invested $64 million over the years through the Gilbert Family Foundation, including $12 million for gene therapy initiatives to address the underlying cause of NF1 and $11 million for vision loss in NF1 patients, which Nick grapples with, according to YooRi Kim, the foundation's scientific officer.

Marc and Alex Cellucci, and their daughter, Maible, 6, and dog Pedalino, pose for a portrait outside of their home in Quincy, Mass. on Tuesday, Aug. 6, 2019. Alex and  Maible both have neurofibromatosis, a genetic disorder that causes tumors to form on nerve tissue.

"With deeper understanding with each of these diseases that we've obtained over time, it's becoming more and more clear that the strategies that you would use to help each of those patients are going to look different," Kim said. 

Even so, she said there is excitement about advances in research on other forms of NF, such as the stem cell line modeling NF2.

There are four embryonic stem cell lines on the registry that model NF1, but the line UM created is the first for the research community studying NF2, according to Smith.

"It means a lot to the couple that somebody is using something that otherwise would have been discarded and instead trying to make it something that can be used worldwide to understand this disease better," he said. 

The stem cell line has been applauded by Sally Temple, scientific director of the Neural Stem Cell Institute in Rensselaer, New York, which uses stem cell technologies to develop therapies that affect the nervous system.

Alex Cellucci, 35, and her daughter, Maible, 6, pose for a portrait outside of their home in Quincy, Mass. on Tuesday, Aug. 6, 2019. Alex and Maible, both have neurofibromatosis, a genetic disorder that causes tumors to form on nerve tissue.

"It's a really wonderful and generous for the parents to do," said Temple, who is also a UM adjunct professor in the ophthalmology department. "When you make these human embryonic stem cell lines, they are essentially a resource forever for the community. It's available and it will be there for (researchers) to use forever in the future. It's not a one-time donation."

She added that this is important for the NF2 community since it is such a devastating disease. 

Marc Cellucci is beyond thrilled, and hopeful of the possibilities for the stem cell line that he and his wife helped create and what it could do for his daughter, wife, in-laws and so many others with NF.

“It all has to start somewhere,” said Cellucci, “where the scientific breakthroughs happen, and the miracles begin.”

kkozlowski@detroitnews.com