A family’s mission: ‘Deep down, we need to know we’ve done everything we can’

The Panwala family (l to r Anil, Leena, Ariya and Alaya) has partnered with JAX to find a cure for their daughter's rare disease.The Panwala family (from left: Anil, Ariya, Leena and Alaya) has partnered with JAX to find a cure for their daughter's rare disease.

Parents of a child with a rare nervous-system disorder partner with the JAX Rare Disease Translational Center to test therapies.

The Panwala family's rare disease odyssey begins

Leena Panwala’s odyssey began in 2015 with a note from her 1-year-old daughter’s daycare center, saying teachers had noticed Ariya’s pupils shaking. Not all the time, the teachers assured her, but noticeable if you sat and watched the child for a bit. 

Panwala and her husband Anil thought Ariya might have a virus or be showing signs of fatigue. They had just returned from a trip to Mexico and started Ariya in daycare not long after. It was a time of transition, and as first-time parents with no medical background and no history of illness, they weren’t sure what to consider cause for alarm.  

“I did not in my wildest dreams or nightmares imagine she was battling anything like this,” Panwala said. 

Within a few weeks, Ariya’s intermittent problem with involuntary eye movement had become constant. So the Panwalas visited their pediatrician, then an ophthalmologist and finally a neurologist, who was the first to suggest Ariya’s condition might be genetic.

Panwala called as many geneticists' offices as she could, finally securing an appointment about two hours from their home in Fairfield, NJ at the Children’s Hospital of Philadelphia. There, Ariya underwent genetic tests and an MRI, but all results came back normal. Panwala later learned that the testing panel didn’t include the gene that causes her daughter’s disease, and so life went on for Ariya without a diagnosis.

At home, the Panwalas saw troubling signs of regression. Ariya began to lose strength in her torso, and her crawling slowed. She never took her first steps, and by the time she was 16 months, she could no longer move at all. 

“We never thought we wouldn’t see her crawl again,” Panwala said, her voice breaking as the memory took its toll. “We never thought there would be a last time we would see her sit up on her own. But it’s all part of her story, which she tells through us.” 

Connecting to JAX in the search for a cure 

Just after her second birthday, genetic testing confirmed Ariya’s diagnosis of Infantile Neuroaxonal Dystrophy (INAD). INAD is an autosomal recessive disorder, meaning it is inherited from two carrier parents who never exhibit symptoms. It is caused by a mutation of the PLA2G6 gene, and while considered rare, may affect hundreds of children in the United States. 

The family launched their nonprofit organization, the INADcure Foundation, in 2017 to fund research, raise awareness and connect other families battling the progressive disease that affects the nervous system. With support from INAD-afflicted families around the world, their objective is to discover and develop a safe and effective treatment for their children.

“Anything you read about rare disease tells you gene therapy is currently the most promising treatment,” Panwala said, “and we need treatments for these kids now.” 

Gene therapy strategy refers to the process of placing a healthy gene into a viral vector (a tool that delivers genetic material into the cells of a mouse model) to express the protein missing from the mutated gene. After six years, INADcure has multiple disease models and a gene therapy strategy and has manufactured vectors that are in various stages of testing. 

To help INADcure deliver proof of concept for the next round of studies, independent gene therapy consultant Neil Hackett, Ph.D., connected the foundation to The Jackson Laboratory’s Rare Disease Translational Center (RDTC) and Vice President Cat Lutz, Ph.D., MBA. 

Delivering proof of concept can be complicated because there many variables to consider, including determining the best route of administration and dosing for the virus. Preclinical data can take up to six months to analyze.

“We want to help INADcure’s program move to the clinic as quickly as possible,” Lutz said. “These children don’t have time for us to try one therapy at a time. Our strategy involves delivering different vectors at the same time to rapidly determine which one is the best therapeutic possible.”  

To that end, JAX will conduct studies to help the foundation generate data strong enough to support a dosing study – in which potential therapeutic doses are tested against each other to see which works best and/or is least harmful – and other studies to test the physiological effects of each treatment.

Testing multiple therapeutics in a meaningful way requires much coordination and planning. “These are big experiments – the type that can only be done in a place like The Jackson Laboratory,” said Jennifer SanMiguel, Ph.D., who is driving the studies as lead scientist in the RDTC. “We have an incredibly talented group of individuals working on this project who are committed to making a difference for the Panwalas and other INAD-afflicted families.” 

Fostering hope for the future

After discovering through Ariya’s diagnosis that they both carry a genetic mutation for INAD, Panwala and her husband usedin vitrofertilization to welcome their second daughter Alaya, who underwent early-detection genetic testing.

“We learned early on that Alaya was not even a carrier, and she was in fact born healthy in October of 2017,” Panwala said.

Panwala said the work she does at the INADcure Foundation serves as her emotional outlet, and that she and her husband always find it uplifting to share their story with others. She takes pride in powering the science of a potential cure, pushing the research that may one day make a difference for future children and families. 

“We knew we would do everything in our power to help our daughter,” Panwala said. “Deep down, we need to know we’ve done everything we can for her, and for all children affected. I know our fellow INAD-afflicted families share this sentiment.” 

 “The patients and families are at the center of everything we do,” Lutz added. “The science and technology definitely enable our work, but it’s the families and promise of therapies that motivate our days.”

Visit the Rare Disease Translational Center site to learn more about JAX’s vision to provide rare disease patients and families with an efficient path from diagnosis to therapy.