Use of antidepressant found to ease anxiety in young girl given Upstaza

Treatment with sertraline, sold as Zoloft, also helped patient communicate

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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An adult hugs a child while also placing one hand on the youngster's head.

Treatment with sertraline, an antidepressant sold under the brand name Zoloft among others, worked to ease anxiety in a young girl with AADC deficiency who had received treatment with the gene therapy Upstaza (eladocagene exuparvovec).

The youngster was able to more effectively communicate, eat better, and walk independently after starting on sertraline, according to the researchers.

The team detailed the child’s case in a report titled “Selective Serotonin Reuptake Inhibitor Treatment Post Gene Therapy for an Ultrarare Neurometabolic Disorder (AADC Deficiency),” which was published in the Journal of the American Academy of Child and Adolescent Psychiatry.

Sertraline belongs to a class of medications called selective serotonin reuptake inhibitors or SSRIs.

Current guidelines for AADC deficiency suggest that SSRIs should not be used to treat patients because they generally are not effective and may in fact worsen disease-related motor problems. However, these guidelines were developed prior to the availability of Upstaza — and this child’s case shows they might not apply for patients who have been given gene therapy.

“This case highlights a need for methods to generate, revisit, and disseminate objective evidence on treatment effects in ultrarare conditions,” the scientists wrote, stressing a need for further research in this area.

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Child was given Upstaza at age 5, with great benefit

AADC is a genetic disorder characterized by abnormally low levels of serotonin and other neurotransmitters, which are signaling molecules nerve cells use to communicate with each other. Upstaza, being developed by PTC Therapeutics, is designed to deliver a working version of the gene whose defect causes AADC deficiency to cells in the brain. The gene therapy is approved in Europe and is currently being considered for approval in the U.S.

The girl at the center of this report, now age 7, was diagnosed with AADC deficiency in infancy. For the first five years of her life, she had no ability to move voluntarily and could only eat via a feeding tube.

She also showed “severe irritability and sleep disturbance,” as well as frequent episodes of abnormal twisting motions known as dystonia, and several weekly oculogyric crises, or instances of an eye movement disorder in which the gaze is involuntarily fixed upward due to spasms in the eye muscles.

At age 5, the child had received one-time treatment with Upstaza. Within one month of gene therapy, her condition improved dramatically: She no longer had any oculogyric crises, she slept better, and was less irritable.

The girl’s motor function also improved after gene therapy. By six months after Upstaza treatment, she was able to sit unsupported and feed by mouth. By 1.5 years after Upstaza, she could walk under her own power.

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Gene therapy’s promise seen in its success for AADC deficiency

Antidepressant worked to ease anxiety and improve walking ability

Cognitive assessments done when the girl was 6 showed she had challenges with cognition and communication compared with what would be expected for a typically-developing child. She also met criteria for autism spectrum disorder, as she engaged in atypical repetitive movements, such as flapping her hands, and had limited ability to engage in typical social interactions.

A psychiatric assessment done the next year also noted that the girl showed signs of notable anxiety — she often seemed fearful when attempting to move objects with her hands or during care routines like bathing, and her mood could quickly shift from laughter to tears.

Behavioral and occupational therapy were not helping with these issues, and the researchers noted that other members of the girl’s family had also reported clinically relevant anxiety.

Because the girl hadn’t experienced any abnormal movements since getting Upstaza, clinicians and the child’s parent made the collaborative decision to try sertraline.

“There are no data to guide psychiatric care post-gene therapy for AADC or other neurologic disorders to date,” the researchers noted.

In this particular case, the treatment “was well tolerated and resulted in marked reductions in anxiety,” the team wrote.

[The child] was able to engage more thoroughly in therapy, including expressing a choice, signing for more, nodding yes/no, [and] using an augmentative/alternative communication system.

After starting on the SSRI, the girl “was able to engage more thoroughly in therapy, including expressing a choice, signing for more, nodding yes/no, [and] using an augmentative/alternative communication system,” the researchers wrote. She also was better able to feed herself and walk independently.

The scientists noted that it’s impossible to draw far-reaching conclusions from this one report, and they also cautioned it’s impossible to definitively conclude whether these improvements were due to setraline, or were delayed benefits from Upstaza, or both. The team called for more studies into the possible use of SSRIs post-Upstaza.

Until there’s well-established information, the scientists stressed it’s important for clinicians to work with patients’ families when making treatment decisions, writing, “collaboration across disciplines and with family partners is essential.”

The use of “novel as well as commonly prescribed therapies [should be] included in case descriptions of rare genetic conditions, as well as in longitudinal rare disease registries,” the team also noted.