There are currently no disease-target treatment options or trials for CLN1. After identifying a patient with CLN1 and two missense mutations, an individual IND for expanded access was approved by FDA using TSHA-118 (development program on hold) provided by Taysha Gene Therapies. The patient was treated with 1e15 vg TSHA-118 via lumbar intrathecal delivery, with steroid and sirolimus immunosuppression. Only mild expected issues with vomiting, fever and lethargy were observed about 72 hours post-delivery, and steroid side effects of sleep disruption, excessive appetite and behavioral dysregulation. This patient had moderate cognitive/adaptive delay but good motor skills at baseline. He has retained generally good motor skills (walking, running, jumping) over two years post-treatment, despite cognitive/language decline. Assessments have been compromised by abrupt vision loss starting about 4 months after gene transfer, progressing to near complete vision loss over the next 6 months, unresponsive to intravitreal TSHA-118 administration to one eye. PPT1 levels in blood and CSF have normalized. MRI has shown ongoing volume loss. The patient has developed drop spells with no EEG correlate that require close monitoring limiting mobility. Based on good safety and normalized PPT1 levels, the FDA approved conversion of the IND to an intermediate-size patient population IND. Three additional patients with at least one missense mutation have been treated, all with minimal-mild neurological symptoms but full vision loss in two. These patients have also had only mild expected vomiting and low-grade fever about 48-96 hours post-infusion and expected steroid side effects. PPT1 levels have normalized in blood and CSF in the second patient. Laboratory testing has not shown significant abnormalities. Ongoing follow up will help determine if TSHA-118 can stop or slow progression in CLN1. It is expected that impact will be largest in patients and symptom domains which are least affected at the time of treatment.