From the pages of Mayo Clinic Magazine.

The first thing the Arndts want you to know about them is their strong faith in God. They say it’s gotten them through some very tough times — mother Tara’s two bouts of cancer (one melanoma, one Hodgkin lymphoma); daughter Kelly’s head wound that sent her to the emergency room in an ambulance; and daughter Madison’s fight with H1N1 flu, which had killed several children in their home state of Minnesota that year.

Madison and Tara Arndt

They knew their faith would see them through another trial two years ago, but Mom and Dad were worried. Doctors at Mayo Clinic noticed lesions on Madison’s eye, and the 11-year-old’s vision was getting worse. Her sight had never been great — she’d gotten her first eyeglasses at age 4, starting with a +3 prescription. Then at age 6, local doctors saw scarring on both eyes and referred her to Mayo.

In the years between 6 and 11, Mayo Clinic worked with Madison and her parents, and Madison’s vision remained fairly stable. But these new lesions worried Mayo Clinic ophthalmologist Jose S. Pulido, M.D., as did the inflammation in her eyes.

Mayo Clinic doctors placed a steroid implant, but soon Madison had headaches and blurry vision. Her eye pressures were extremely high at 43 (normal eye pressure ranges from 12 to 22), which Dr. Pulido relieved through a prescription of four eyedrops and a pill. And even though Dr. Pulido was doing everything he and colleagues could to control Madison’s symptoms, the future frightened her family.

“We worried about the unknown,” Tara says. “That was the scary part — is she going to go blind? As a parent, you just want to know what’s wrong. Let’s get this fixed.”

Doctors were determined to provide answers to Madison’s family. They performed more tests — visual field, blood, urine, DNA — and discovered Madison has a rare recessive form of the already rare Best disease, an inherited form of macular degeneration. A recessive form of the disease means both her mom and dad, Sean, carry a mutation in the gene that causes the disease, and Madison inherited them both.

Best disease affects the macula, which is part of the retina. Usually the disease doesn’t impair vision until later in life, which made Madison’s early onset tough to detect. And her even rarer recessive form makes it just as difficult to predict how the disease will progress, though doctors believe she’ll never go totally blind. However, legal blindness is a real possibility, and there is currently no treatment to prevent it.

The news shocked the Arndts and scared Madison, who began to cry as they left the doctor’s office after the diganosis. Her mom gently joked that God gave Madison the Best eye disease there was, and then reminded her that God had a plan for her. Perhaps her suffering would help others.

A year later, the Arndts would find out how right Mom was.

A New Optimism

In August 2013, during Madison’s routine checkup at Mayo Clinic, Dr. Pulido entered the exam room very excited. Mayo Clinic had just hired Alan D. Marmorstein, Ph.D., one of the world’s experts on Best disease. And Dr. Marmorstein wanted to apply the power of Mayo to develop an innovative stem cell treatment to help Madison. If successful, the treatment could help people around the world with Best disease.

Dr. Marmorstein has worked on Best disease since 1998, when the gene that causes the disease was discovered. He came to Mayo Clinic because he believes bioengineered stem cells might halt the disease’s progression, or even cure it, but the institution he was at previously didn’t have such capability. Mayo Clinic and its Center for Regenerative Medicine do.

The Center for Regenerative Medicine is conducting several stem cell clinical trials. Its experts are perfecting the viability of stem cells taken from adult fat tissue as well as pioneering methods to convert skin cells into bioengineered stem cells, then differentiating them into other cells. One research group converted skin cells into functioning heart tissue that beats in the petri dish.

What’s more, the center houses the Regenerative Medicine Biotrust, which would enable Dr. Marmorstein to test a number of possible treatments at once.

As soon as he arrived at Mayo, Dr. Marmorstein partnered with the Biotrust to develop a regenerative medicine protocol focused on Best disease. Biotrust experts would do a bulk of early work required to use cells as therapy — take biopsies from patients, convert the biopsies into bioengineered stem cells, and validate and store the cells — as well as train his staff in how to handle and apply these specialized cells.

“We went from being experts in Best disease to being able to apply stem cells to Best because of the assistance of the Biotrust experts,”

Dr. Marmorstein says. “I can’t emphasize how critical they have been for this work. If you start doing this on your own, it’ll take years. But they took what would have been a very steep learning curve and made it a very shallow one. We’ve been able to accomplish in a year what would have taken five years anyplace else.”

A Permanent Fix

On Valentine’s Day, Madison and her mom traveled to Mayo Clinic in Rochester, Minnesota, to give blood and skin samples. Soon Dad donated, too.

The Biotrust converted Madison’s skin samples into bioengineered stem cells and is now helping Dr. Marmorstein and colleagues convert those cells into functioning retinal pigment epithelium (RPE) cells, the cells affected by Best disease.

Because these cells are alive, the team will be able to test, in the petri dish, a number of solutions for Madison before ever treating her. The first solution the team will try is gene therapy, which is already being performed in other eye diseases. The team will also use the cells to test a whole host of drugs that show promise but are not approved by the Food and Drug Administration for this disease.

However, both of these approaches have drawbacks. Gene therapy might lead to the unregulated expression of the protein involved in the disease, and medications always carry the risk of side effects.

Dr. Marmorstein believes the most effective solution may be to remove Madison’s damaged RPE cells and replace them with RPE cells bioengineered from her skin cells. It would be a permanent fix with no side effects since Madison will be treated with her own cells.

“Gene therapy doesn’t remove the bad protein, and finding a drug would mean Madison would be on that drug the rest of her life,” Dr. Marmorstein says. “The best approach may well be to replace her RPE cells with new ones in which we have restored the gene.”

Alan Marmorstein, Ph.D.

While Dr. Marmorstein develops these treatments, Madison and her family continue to work with Dr. Pulido to control the symptoms as best they can, and the Arndts’ lives go on. Madison dances on the high school dance squad, plays flute in the junior high band, goes to football games and dances with friends, and reads whatever she gets her hands on. The family goes fishing when they can. And though Madison is still only 13, they are beginning to think about college. (Madison is considering animal medicine, but doesn’t like the idea of giving shots.)

Whatever comes their way, the family is confident that God will see them through and Madison will get the help she needs.

“The future always brings more technology, and I know our prayers are being answered and believe Mayo will help stop Madison’s disease from progressing,” Tara says. “That gives us hope for her future.”

Tags: alan marmorstein, best disease, biotrust, eye disease, Jose Pulido, Madison Arndt, Mayo Clinic, News, regenerative medicine, Research, stem cells, Tara Arndt