UX055 AAV9 Gene Therapy for the potential treatment of CDKL5 Deficiency Disorder (CDD)

CDKL5 Deficiency Disorder (CDD): a severe and debilitating neurological disorder with epileptic seizures starting early in life

CDKL5 Deficiency Disorder (CDD) is a rare early infantile epileptic encephalopathy. CDD is characterized by the onset of seizures at a very early age (usually in the first months of life) and severe developmental delay, hypotonia, and cortical visual impairment. CDD has an estimated global incidence of one in 40,000 – 60,000 live births. Infants and children with CDD can present with a broad range of clinical symptoms and severity. CDD symptoms include early-onset, intractable epilepsy and neurodevelopmental delay impacting cognition, motor function, speech, and visual function. Other symptoms of CDD include gastrointestinal and sleep disturbances. Most CDD patients require around-the-clock care and management of their complex symptoms.

CDD is an X-linked dominant disorder caused by genetic mutations in the CDKL5 gene, which provides instructions for making the CDKL5 protein that is essential for normal brain and neuron development. CDKL5 loss of function results in impaired communication between neurons. There are currently no approved treatments that address the root cause of the disease.

Evaluating UX055 to improve CDKL5 protein expression in the brain

UX055 is an investigational gene therapy in pre-clinical development for CDD that aims to deliver a functional copy of the human CDKL5 gene to the brain using an Adeno-Associated Vector Serotype 9 (AAV9). This vector contains a neuron-specific promoter intended to drive expression of functional CDKL5 protein specifically in neurons. UX055 is delivered via an injection into the cerebrospinal fluid space to target the central nervous system. Early preclinical studies of UX055 showed motor and cognitive behavioral improvements in a mouse model of CDD. In addition, UX055 treatment led to correction of neuronal hyperexcitability in a human brain organoid model derived from induced pluripotent stem cells from patients with CDD.