BPAN

Wearing a white T-shirt with a massive star in sparkling shades of pink, yellow and seafoam green on the front, Morgan Kozole sits in front of a fold-up chalkboard in the living room of her family's Detroit-area home and starts to draw.

Using pink and yellow chalk, she sketches Mickey and Minnie Mouse. The Disney characters are dominant fixtures in the 5-year-old's life and therefore become a soundtrack for the Kozole family: Morgan constantly saying "Mickey," with her long, blond ponytail bouncing to whatever song happens to be playing on the Mickey Mouse Club.

"These are the two Mickeys," Morgan says, pointing to the chalkboard. Her mother, Detroit Lions senior vice president of business development Kelly Kozole, explains that this is her way of communicating that she would like a visitor to draw Mickey too. If it's close, Morgan accepts it. Another Mickey to fawn over.

For Morgan's birthday earlier this year, the family went to Disney World. On this trip, the Kozoles saw what they had longed for: the potential of progress.

"She knew where we were. She knew Mickey Mouse," Kelly said. "Before, she wouldn't go to the characters, and now she's jumping up and down, hugging. She really, along those lines, is also really into birthdays.

"The 'Happy Birthday' song. Before that, she was just kind of looking. Sometimes it was too much for her with everyone singing -- sometimes loud noises are too much. This year, we had to sing 'Happy Birthday' to her three times."

Birthdays, for children, are happy occasions -- reasons for grand celebrations of progress toward adulthood. For the rest of Morgan's family it is more complicated.

Morgan has a rare neurological disease called beta-propeller protein-associated neurodegeneration, known as BPAN. It's a disorder, more prevalent in girls than boys, that causes delayed development and seizures, communication issues and, sometimes, motor dysfunction. It's unclear exactly how many people are living with BPAN worldwide due to its rarity, although Dr. Sami Barmada, a scientist at the University of Michigan studying BPAN, estimates roughly 500 to 600 people.

It's rare enough that Dr. Henry Paulson, the director of the Michigan Alzheimer's Disease Center, said there are experts in neurodegeneration who are unfamiliar with BPAN. While Kelly is trying to advocate for her daughter and others with BPAN through fundraising for research, science moves only so fast.

The Kozoles understand that. So birthdays for the family aren't always happy. They are a reminder of what could come.

"That ticking time clock," Kelly said. "Every birthday isn't exciting for me for her. Because it's one year closer to when this bomb is going to go off." 

BPAN's rarity makes the reality heartbreakingly simple: There are very few effective treatments, little research and no cure. As Morgan learns how to organize her Peppa Pig characters and learns new words on her iPad -- her future looms.

At some unpredictable point in Morgan's teen and adult years -- the average is around age 25, according to Barmada -- development will just stop. Progress will decline and, in some cases, disappear. Those afflicted with BPAN begin suffering from progressive dystonia parkinsonism -- making it difficult to walk, talk or stand.

"Any day," Kelly said, "it could be like, 'Oh, your daughter's gone.'"

When Morgan was born on Jan. 12, 2015, she was, largely, a healthy baby. She was a little jaundiced but nothing worrisome.

When she would go to the doctor's office for shots, Morgan didn't cry. It was a little abnormal, but when you're a parent of a young child, no crying is viewed as a minor miracle. Kelly and her husband, Kevin, took this as a sign of a tough kid. Nurses even said how great it was.

Looking back, it was a warning sign that something was wrong. BPAN causes a high pain tolerance. Before long, more concerns popped up. Morgan wasn't crawling at nine months, wasn't walking at a year. Expected milestones passed without Morgan reaching them. Kevin and Kelly put her in therapy in late 2016 to work up to these childhood progressive traits and began researching potential causes. They wouldn't find an answer for more than two years.

"She was diagnosed with cerebral palsy at first. One doctor diagnosed her with that, and then another, our neurologist, said she doesn't have that," Kelly said. "Then there was speculation but not a full diagnosis she had autism, so we did all the tests for that.

"So through this kind of journey of trying to find out what was wrong, it was exciting that she didn't have something that you were going to this test for, but you still had so many more questions as you were eliminating all these potential diseases that she could have."

Befuddled, they began genetic testing and in November 2018 received a letter about a mutation on Morgan's WDR45 gene. Kelly Googled it, stumbled upon BPAN and freaked out, calling their neurologist. The neurologist told Kelly not to worry -- BPAN was very rare, and Morgan didn't have it.

Doctors diagnosed her with epilepsy because of seizures. Morgan took Keppra, which helped accelerate her vocabulary to about 50 words, typical for a 1-year-old, when she was 3. Then doctors said no, it wasn't epilepsy either. 

Another meeting with another neurologist led to a different diagnosis. Three days after she and Kevin returned to Michigan from Super Bowl LIII in February 2019, they received a call. Doctors figured out what was wrong.

It was BPAN.

"In my mind, it's worse than cancer," Kelly said. "How is this even possible? That this can even be so painful for kids later on in life. You try so hard to gain all these abilities, and then early adolescence or early adulthood, it's just [gone] one day, and I've seen a lot of these stories.

"There's a BPAN Facebook website, and that's where the doctors sent us. There's no cure. There's no therapy. 'Go to this website.' That's what I was told."

For months Kellycried, angry and heartbroken. The Kozoles initially told their families and no one else.

In May 2019, Kelly went to her first Neurodegeneration with Brain Iron Accumulation (NBIA) conference. She met other parents, heard their stories and began the new normal.

She used her skills -- organization, fundraising and business -- to brainstorm ways to help. Hardly anyone had researched BPAN. Without it, there would be no chance for a cure -- not in Morgan's lifetime, which could reach her 40s, and not in the lifetime of those who might come after.

She shared what was happening with her boss, Detroit Lions president Rod Wood, and his wife, Susan, using a website link to explain BPAN. Wood knew something was wrong because of texts and emails saying they had to take Morgan to this specialist or that appointment.

"As that was confirmed and became her reality, she is now able to talk about it, in a way," Wood said. "Because she's full bore on trying to help generate awareness and financial resources to find a cure for it.

"She went from the unknown to the very tragic known to, 'OK, what are we going to do about it?'"

Kelly consulted her aunts, both of whom worked in medicine. Linda Narhi worked in biotechnology for Amgen for more than 30 years; Dr. Diane Narhi was the first female chief of staff at Simi Valley (California) Hospital. From talking with another group of fundraising BPAN parents -- BPAN Warriors -- Kelly found a guide.

"Any day, it could be like, 'Oh, your daughter's gone.'"

If her aunts had not been resources, she might have joined BPAN Warriors. But Kelly admittedly needs to be in control, and this was her daughter. She needed to manage this herself. She created a nonprofit called Don't Forget Morgan.

Kelly's aunts provided guidance, and Wood offered contacts he had in the finance industry and Silicon Valley. Wood and Lions general counsel Jay Colvin sit on the board. Other Lions coworkers -- with Wood's blessing -- built the website, designed the logo and created social media plans and the first pitch video for Don't Forget Morgan's rollout in 2020.

Progress started with a $15,000 grant to help with a mouse model study at Sanford Research in South Dakota, with another, larger, potential grant to come. In recent months, Kelly has focused largely on fundraising, and another parent of a child with BPAN, Christina Mascarenhas Ftikas, has focused on the medical side of the nonprofit.

"This is why I'm here," Kelly said. "I'm supposed to be a vehicle to get all of this awareness and hopefully a cure for BPAN so the child one, two, three, five years from now, there is hope.

"There is no, 'Go to Facebook.' There is something where you can actually give a parent, 'Here's the symptoms to look for.'"

About an hour away in Ann Arbor, Michigan, Kaci Kegler and her husband, Brian, had been in the same Facebook community. Kelly, new to the group and looking for a nearby connection, wrote Kaci a message.

"Hey, my daughter was just diagnosed, could we connect?"

Kaci understood. She did the same thing, reaching out without success in 2016 after her daughter, Elle, was diagnosed. Kaci wanted to be a resource.

They talked for an hour. There wasn't much Kaci could say to soothe her. Kelly pinged a year later with another message: I'm starting a nonprofit. Kaci offered to help.

Despite suffering from BPAN, Morgan is like any other 5-year-old who enjoys playing with her brother, Connor. Michael Rothstein

Days later, on Feb. 28, Kaci and her husband, Brian, an assistant athletic director for development at the University of Michigan, had their yearly fundraiser for BPAN research on Rare Disease Day at Pizza House in Ann Arbor. They met a doctor who had a connection to researchers at Michigan.

"I literally came home and texted [Kelly] and was like, 'Oh my gosh, we may have inroads,'" Kaci said. "We just started texting. I have never met Kelly face-to-face. We still haven't. But we've texted a lot and we've emailed quite a bit.

"It just kind of started."

By summer, they went from nothing to putting pieces in place for a full-fledged research project with a two-year, $140,000 grant for Barmada and Dr. Jason Chua to help start to solve BPAN.

Chua was working on the regulation of autophagy, which is the cleaning out of damaged cells, and studying BPAN became a natural extension of the work he had already been putting in. BPAN alters that in neurons. Barmada said Chua's research provided a "rare win-win situation" to potentially help with BPAN and other diseases too.

"There are a set of questions in BPAN that nobody has the answer to," Barmada said. "And Jason and myself, we just seem to be in the right position, the right place to be able to help out."

The goal is to understand what is happening within BPAN itself and how people end up with it, while also trying to find therapies for existing patients. Within a year, they are hoping to grow stem cells from people with BPAN in their lab, allowing for the creation of their own stem cells missing the WDR45 gene. Then they will try to either replace the gene or "stimulate autophagy through genetic or pharmacologic means," Barmada said. The hope is this can prevent neurodegeneration.

So far, they've hired a research assistant to work with Chua, developed tools to manipulate the gene using the genome-editing tool CRISPR and applied for approval from Michigan and the institutional review board to get skin biopsies to obtain stem cells from BPAN patients.

It's a process, but it's also a start.

After partnering with Michigan and Sanford, Don't Forget Morgan also began working with Dr. Kathrin Meyer, a researcher at the Center for Gene Therapy at Nationwide Children's Hospital at Ohio State.

"Solving this disease is going to require more than Jason and Sami," Paulson said. "It's going to be a first shot across the bow, but it's going to require more than that. I'll say this, being in the field for a long time. Scientists who are coming up the pike say they want to look at Alzheimer's, want to look at epilepsy. They don't say, 'I want to look at a rare disease.'

"The only way to solve a rare disease is to get someone hooked. Sometimes when you hook a really good one, as I think we have with Jason here, you hook them for life and they make a difference."

Morgan is bouncing around the Kozoles' suburban Detroit home on this late August day. They just returned from northern Michigan, and having two kids, especially one with special needs, makes tidiness unrealistic.

COVID-19 changed things. Morgan hadn't been to many of her therapies for months. Online school barely kept her attention. There was concern she would have regression in her learning. Instead, her speech advanced by being around Kelly, Kevin and her older brother, Connor, all day. She has sung more songs recently to help increase her vocabulary. Sometimes, she'll listen 20 times in a row.

"Even more than that," Connor said. They aren't sure how much she's truly learning versus memorization. But it is something.

Morgan Kozole has inspired her mother, Detroit Lions VP Kelly Kozole, to marshal researchers and other advocates to develop a cure for BPAN, and perhaps help future generations of children who live with the disorder. Michael Rothstein

The family gathers inside Morgan's bedroom -- complete with a special Haven Bed with a zipper to keep her safe from wandering around at night, when she could accidentally turn on the stove and hurt herself or others -- sleep disorders are another BPAN issue. She sits on the floor and starts playing with her small, yellow dollhouse and a fake ice-cream maker. Kelly asks for an ice cream. Morgan makes one for herself instead and pretends to eat it.

Later, outside, Morgan kicks a soccer ball and plays a modified game of catch with a squishy football. Football, no surprise, is big. She says "hike" a lot. "She knows that term," Kevin says, laughing.

In these moments, Morgan seems like any other young child. She attends St. Hugo of the Hills Parish School in Bloomfield Hills, Michigan, but has a one-on-one para nanny to help. She interacts with people, often overly affectionate.

Sitting at the kitchen table after playtime outside, she plays with Starfall, a children's learning app, on her iPad. They hope it accelerates her word recognition. Morgan is entranced watching "Farmer in the Dell" and using her hands to eat orange slices and Cheerios. She needs a mirror in front of her to provide her a target for her mouth. She listens to books, another way to try absorbing information.

Morgan can now count to 20 and say three sentences in a row. Kelly and Kevin have tried to give Morgan a normal life in an abnormal situation, but they worry about the future -- what she won't have and won't be able to experience.

But Morgan has changed some of that outlook too.

"Focus on how she is so loving and has so much pure joy. A lot of parents of special needs [kids] say you can learn so much from these kids, and you really can," Kelly said. "She is, every morning, just so happy, and 'Mama!' Hugs and kisses to strangers. She has none of those behaviors you learn as an adult where you're not kind to people or you don't want to talk to someone.

"She is just open arms, will give you a hug and is so loving, and it's like, 'Wow, this is really what life is about.'"

https://www.espn.com/nfl/story/_/id/30371811/detroit-lions-vp-tries-save-daughter-rare-disease

Courtesy of a colleague

See:  https://childnervoussystem.blogspot.com/2018/02/beta-propeller-protein-associated.html