The Middletown Press (Middletown, CT)
Yalie with disability ‘just astonishing’
Yale student tells how new FDA approved drug treats her rare genetic disease
“I’ve been in the operating room over 20 times my entire life. I’ve been in clinical research as long as I can remember.”
Arya Singh, Yale University junior
NEW HAVEN — For Arya Singh, a junior at Yale University, the weakness in her muscles is a challenge, not a barrier.
President of the Yale Undergraduate Legal Aid Association, an undergraduate teaching assistant in professor Howard Forman’s “Health Economics and Public Policy” class and a member of the New Haven Commission on Disabilities, she is making her mark on Yale and the city.
She has even written a children’s book, “Courageous Calla and the Clinical Trial,” based on her experience helping to develop three drugs.
Singh, 20, has had spinal muscular atrophy her whole life. She has used a wheelchair since she was 5. She will tell you she requires “extreme dependency on friends and family for tasks of daily living that most people would not think about.” Just raising her hand in class takes effort.
Now that she is on Evrysdi, a drug recently approved by the Food and Drug Administration, she no longer will have to undergo a lumbar puncture, in the operating room under anesthesia, in order to receive medication that keeps her muscles from weakening further.
“I’m a full-time student but I also have three hours of physical therapy every day,” she said. “I’ve been in the operating room over 20 times my entire life. I’ve been in clinical research as long as I can remember.”
Those clinical trials have kept Singh’s condition somewhat stable for years, but they have not been without pain and risk. Spinraza, which must be injected into the spine, was one of the three clinical trials in which she has taken part. While it helped keep her somewhat stable, it was “incredibly invasive” to receive, she said.
“A lumbar puncture is a really dangerous procedure in that you can have leakage of spinal fluid,” she said. “That happened to me and I was out of school for three weeks
on and off for the rest of the year, because a side effect of that is you get these incredible headaches. … You have to lie down in order for that to stop.”
Evrysdi (Genentech’s trade name for risdiplam) differs from Spinraza both in how it’s administered and in its effects.
“What’s important about this drug is that it delivers this protein all over the body instead of just the central nervous system, and I think for most SMA patients they would say that what they notice is the fact their muscles are getting weaker. You don’t really notice loss of nerve function,” Singh said.
“What I have said time and time again is that I’m so grateful that I was part of that trial,” Singh said of Spinraza. “I think that drug is lifesaving.” Evrysdi, though, “achieves more than I think Spinraza did for me in a way that is less scary, less invasive and less dangerous.”
Evrysdi “doesn’t disrupt my daily life and that is hugely beneficial to anyone, but especially someone who’s a college student,” Singh said. “It improved my quality of life in an unparalleled way.”
Targeting a backup gene
Spinal muscular atrophy is a genetic disorder, which in severe cases can be fatal. The SMN1 and SMN2 genes tell the body to create survival motor neuron (SMN) protein, which maintains the neurons that transmit signals from the brain to the muscles. “SMA is caused by a mutation in the SMN1 gene,” said Kelly Howell, associate director of the SMA Foundation, which was founded by Singh’s parents.
The SMN2 gene is a backup to SMN1. It does not produce SMN protein as efficiently as SMN1, but people can have multiple copies. “There’s a little bit of luck involved with SMA because it does have the backup gene that therapeutics can target,” Howell said. The more copies of SMN2 a person has, the less severe the disease will be. Evrysdi targets SMN2 throughout the body to increase the amount of protein created.
Spinraza “also targeted SMN2, but it only reaches the motor neurons in the spinal cord,” Howell said.
Singh credits the clinical trials she has participated in with her being able to live a full life with a progressive disease.
“I would argue that the most challenging part of SMA is not being able to keep up with the disease,” she said. “You acclimate to your life and then you lose function. For me the ability to stay at my baseline and stay stable is more than I could have ever asked for. Improved strength is only a huge bonus.”
Evrysdi has helped a great deal in stopping the regression in her muscle strength in the three years Singh has been part of the clinical trial. But she said she knows she “is coming from a place of extreme privilege and not what would be the normal path for someone with SMA at all.”
Relying on friends
It’s not only the medications that have helped Singh achieve what she has, though. She knows how dependent she is on friends, family and medical professionals.
Tiana Lopez, who has known Singh since their first year at Pauli Murray College, is one of those friends.
“She’s always so positive and always willing to persevere,” Lopez said. “I really think that even though she has these extremely harmful health scares and health issues, you would never know it because of how positive she is, how she is able to put you first.” That attitude allows Singh “to experience things in the fullest way,” Lopez said.
Another friend at Yale, Solana Craig, said of Singh, “I
think she’s the best friend anyone could ever have. She’s so genuinely interested in your life, which is a great quality.” Singh and Craig often would leave campus to have dinner downtown. “She’s possibly the most social person I know … but she’s also the best student I know,” Craig said. “She always has her work done and on deadline.”
For Singh, it’s just natural to care about those on whom she depends. “Empathy has become really important to me,” she said. “My ability to live my life is entirely dependent on other people being there for me and other people’s goodwill. I feel that they do so much for me.”
She knows that when she goes to Blue State Coffee, someone will open the door. A friend will help put her books in her backpack or open a water bottle. “Because of SMA, my life has been one where I have to think 20 steps ahead,” she said.
A family foundation
Singh was diagnosed with spinal muscular atrophy at 18 months old. Her parents, Loren Eng and Dinakar Singh, launched the SMA Foundation shortly thereafter. The foundation is “a unifier of pharma and government and patient groups in essentially funding research that then went into the development of these drugs,” Arya Singh said. “So I’ve collaborated with pharma companies for almost two decades now.”
In that time, she has learned that medical research can be difficult on the patients who volunteer to take experimental drugs. She brings her experience to her
studies. In one class, “Communicating Pain,” she wrote a paper about “the pain that patients feel in clinical trials and how that’s often minimized in advertising of drugs.”
Her major is the history of science, medicine and public health. “It’s obviously very niche,” she said. “I love it. I’ve loved every single class.”
Her classes have included “Global Health: Responses and Challenges,” “Bioethics and Law” and “Media and Medicine in Modern America.” Other than last spring, when Yale did not issue grades because of the COVID-19 pandemic, she has received an A on each one.
She did so well in Forman’s “Health Economics and Public Policy” that this semester she is an undergraduate course assistant, creating lesson plans, acting as a gobetween with students and
running the online technology.
“In the all-around picture, she’s just astonishing,” Forman said. “I can’t imagine anyone being better. … She’s just objectively one of the most extraordinary students you could ever know.”
Forman said Singh has also helped raise awareness of SMA and disabilities. “She’s advanced people’s understanding of her disease and people with challenges,” he said. “She has really helped people understand challenges in ways that other people have not.”
A range of severity
Spinal muscular atrophy is a relatively rare disorder, affecting one in every 6,000 to 10,000 newborns, according to the SMA Foundation. About one in 50 people is a carrier, meaning they have mutations in the SMN1 gene.
When both parents are carriers, their children may inherit two defective copies of the gene and have SMA.
There are several types of the disease. Babies born with the most severe type often die before they turn 2. With Evrysdi, 90 percent of infants reached 1 year old without needing permanent ventilation, said Dr. Dalia Moawad, head of neurological rare diseases and U.S. medical affairs at Genentech. Without it, “most if not all would require permanent ventilation,” she said. Another study measured motor function in patients between 2 and 25.
“When we look at the SMA community and the status of available treatments just a decade ago … it’s a very hopeful time for the community,” Moawad said.
An early diagnosis
Singh said her disease is about the middle of the spectrum, between types 2 and 3. “We thought she was a perfectly healthy child at birth,” said her mother. But by the age of 1, Arya was walking with a stiff-legged gait.
“All of a sudden, she would be standing and just crumbling under the weight of just standing and get badly injured,” Eng said. Singh was diagnosed with SMA two days before her brother Kiran was born. Neither he nor their sister, Tara, have the disease.
“She’s been blessed by a really great community, generally, of students and parents who are incredibly supportive,” Eng said. Singh attended the Friends Seminary in Manhattan, where she lives, a Quaker school that is the oldest coed school in New York City. When she graduated, she gave the commencement speech.
“I think she’s figured out a way to take things that might be impossible and turn them into the possible,” Eng said. “She really has that grit. … She really has the tenacity to make a happy day out of every day.”
$150 million invested
Eng and her husband decided to do what they could and started the foundation. “We didn’t know if we can create a drug, but you might as well try,” she said. The foundation has spent $150 million to sponsor research into treatments.
“We have three federally approved drugs that we have helped get across the finish line and we have had lots of failures along the way,” Eng said. In addition to Spinraza and Evrysdi, the FDA has approved Zolgensma, a gene therapy for patients under 2 years old. Evrysdi was developed under an agreement between the foundation, Roche and PTC Pharmaceuticals. Genentech is part of the Roche Group.
Howell said, “Even though we have a lot of successes, the three approvals, we still see an unmet need.” Future research needs to go toward regenerating motor neurons, increasing muscle strength, she said.
Helping children understand
Singh’s children’s book, illustrated by Julia Yu, a family friend, is one more way she has taken the message to children who may be overwhelmed by the idea of taking part in a clinical trial. It wasn’t easy for her.
“It’s essentially rooted in my experience in clinical research my whole life,” often with mixed feelings, she said. “Something that I’ve struggled with a little bit is the immense gratitude that I have felt to be in clinical research.”
She said when she was given a dose of Spinraza on her 10th birthday, she cried in the operating room and told her mother, “I don’t want to be here.” “And my mom turned to me and said, ‘This is the greatest birthday gift you could have ever had.’ I was 10 but that’s one of the moments I look back on and really think about and still remember.”
“I think that what was always challenging for me was I knew that that was true and I knew there were countless and countless doctors and scientists and researchers fighting so hard for making my life better essentially,” Singh said. “Still, it was something no one else that I knew was going through. It was something that I didn’t really understand was happening to me.”
She said she hopes the book will offer adults as well as children “this very digestible way to understand what clinical research is like … And my hope is that it ultimately offers children especially with a source of education, but also comfort and encouragement that they’re not alone in what they’re going through.”