study for the treatment for cln7 disease

Conditions: CLN7

Summary: this is a phase 1 open-label, single-administration of gene therapy agent aav9/cln7, administered intrathecally into the lumbar spinal cord region of pediatric patients with cln7 batten disease. this study consists of a one-time injection of aav9/cln7. there are two cohorts with a low dose and a high dose. the primary objective for this clinical study is to evaluate safety. the secondary objective is to determine the efficacy of aav9/cln7. the secondary outcome measures include motor, cognition and intelligence assessments. the exploratory outcome measures include visual impairment assessment, cognitive evaluations, brain magnetic resonance imaging (mri), electroencephalogram (eeg), electrocardiogram (ecg) and echocardiogram (echo).


Eligibility criteria:
inclusion criteria: * 1-18 years of age * clinically symptomatic patients with diagnosis of cln7 based upon molecular testing with homozygous or compound heterozygous and pathogenic mutations in mfsd8 gene with symptom onset before age 4 * patients selected to be included in this study will have no more than moderate severity of the disease and will have to meet the following criteria; not dependent on chronic invasive ventilatory support and have either * expressive language sub test on mullen and/or vineland consistent with an age equivalent score of a 2 year 0 month old. this means they should have 20-50 words (all comprehensible) in their vocabulary and putting 2-3 words phrases in a sentence or, * patients can complete and obtain a score of 2-3 on gmfm sub domain e (walking, running \& jumping) item 67 (ie with 2 hands held can walk 10 steps forward) * written informed consent provided by participant/parent/guardian and willingness to participate and comply with all the study related visits and procedures. assent provided by children 10 -17 years old based on their ability to understand the risks and possible benefits, and the activities expected of them as participants. exclusion criteria: * diagnosis of a second neurodegenerative disease or another genetic syndrome with a progressive course * hypersensitivity to any drugs used per procedural protocol * inability to tolerate anesthesia or study procedures * advanced stage disease defined by the use of chronic invasive ventilatory support (tracheostomy with ventilator dependence) and a non communicative status * concomitant illness that places patient at risk for gene transfer or gene transfer related procedures and immunosuppression * active, symptomatic viral infection (including but not limited to hiv or serology positive for hepatitis b or c, or covid-19) at the pi's discretion * bacterial infection requiring antibiotics within the 6 weeks prior to infusion * new antiepileptic medications initiated within 90 days of infusion * status epilepticus within 30 days of infusion * generalized tonic-clonic seizure without returning to baseline within 24 hours of infusion * family is unwilling or unable to participate with required follow-up assessments * abnormal lab values that are clinically significant: * platelet count \< 100,000/mm3 * abnormal absolute neutrophil count (anc) of \< 1000/mm3 * persistent leukopenia or leukocytosis (total white blood cell count \ 15,000/mm respectively) * significant anemia (hb \<10 g/dl) * abnormal prothrombin (pt) or partial thromboplastin time (ptt) * abnormal liver function tests (\>2 x uln or \> 2 x the baseline value at time of dosing) * abnormal pancreatic enzymes (\>2 x uln or \> 2 x the baseline value at time of dosing) * renal impairment defined as urinary protein concentration greater than or equal to 0.2 g/l on 2 consecutive tests * any other abnormal lab values that are clinically significant per pi's discretion * if labs are abnormal, these can be rechecked during the screening period. if labs normalize with or without intervention, patient can be enrolled at the discretion of pi. * contraindications for intrathecal administration of the product via lumbar puncture, such as bleeding disorders or other medical conditions (e.g., spina bifida or clotting abnormalities) * contraindications for mri scans (including but not limited to cardiac pacemaker, metal in the eye, aneurysm clip in the brain, etc.) * history of or current chemotherapy, radiotherapy, or other immunosuppression therapy within 30 days preceding screening (corticosteroid treatment may be permitted at the discretion of the pi) * receipt of any other investigational agent within the previous 3 months * positive beta hcg pregnancy test (females of child bearing potential will have a pregnancy test on day -1) * any other medical condition that puts the subject at increased risk of adverse events related to the investigational product or study-related procedures.

Keywords: cln7 batten's disease aav9/cln7