Our unique understanding of the complexities of neurologic systems allows us to turn clinical potential into clinical meaning. The Ovid pipeline includes several candidates that would potentially be the first to make a meaningful impact in the lives of individuals with certain rare neurological conditions, and all address significant markets.
Angelman syndrome (AS) is a genetic disorder in which the still-developing brains of young children are overloaded with excitatory neuronal signals, leading to a range of severe neurological symptoms affecting behavior, sleep, learning, motor skills and communication, and which are present throughout life. Many people with AS also suffer from epilepsy. The key deficits are in:
• Behavior: Heightened hyperactivity and anxiety leading to maladaptive behaviors such as biting and pinching
• Sleep: Increased nighttime awakenings and diminished total sleep time
• Learning: Impaired cognitive performance and memory loss
• Motor: Uncoordinated movements, tremors, and abnormal gait limit mobility and independence with walking
• Communication: Significantly delayed development with little or no verbal speech, often leading to frustration and aggression
• Epilepsy: Those with epilepsy most frequently experience atypical absences, generalized tonic-clonic, atonic or myoclonic seizures. Angelman syndrome (AS) occurs when a mutated gene, UBE3A, creates a nonfunctional protein of the same name. Without functional UBE3A proteins, the levels of GABA, one of the most important neurotransmitters in the brain, are absent or low in the extrasynaptic space, which is a key area surrounding the space between nerves and where each nerve passes signals from one to the other. The absence of GABA in this area greatly reduces tonic inhibition, a critical process in neurons (brain cells) across the brain.
AS was first described in 1965—yet in over 60 years not a single treatment option has been approved. There is an urgent need for effective, disease management treatment options. The neurological dysregulation in AS results in significant impairments that can be as difficult for individuals with AS to manage as it is for their caregivers to continuously manage:
• Living with AS: Individuals with AS require around-the-clock care and are unlikely to ever live independently
• Caring for someone with AS: Caregivers constantly supervise their loved one with AS, often experiencing their own stress, anxiety and exhaustion in co-managing symptoms.
Fragile X syndrome (FXS) is an inherited disorder characterized by an overload of excitatory signals in the brain, leading to significant intellectual impairments that can be difficult to manage for both individuals and caregivers. The key disturbances are:
⦁ Behavior: Hyperactivity, anxiety and increased sensitivity to auditory stimuli
⦁ Sleep: Disrupted sleep patterns
⦁ Learning: Cognitive dysfunction
⦁ Motor: Reduced fine motor skills
⦁ Communication: Delayed speech development and impaired use of language (exacerbated by concomitant autism)
Fragile X syndrome (FXS) is caused when the presence of a mutation on the FMR1 gene (located on the X chromosome) disrupts signaling pathways in nerve cells across the brain. This signaling shutdown causes the production of GABA, one of the most important neurotransmitters in the brain, to be reduced and plummet in key areas surrounding the space between nerves and where nerves pass signals from one to the other. The absence of GABA in this area greatly reduces a critical process in each cell and across all of the brain, called tonic inhibition. Tonic inhibition is crucial as it modulates the ability of cells in the brain to distinguish a real signal from noise—and without it leads to the severe symptoms of Fragile X.
There is a significant unmet medical need as there are no approved therapies that treat the underlying cause of the condition. Current treatment options are limited to physical, behavior, communication, and symptomatic therapy—as such a large, multidisciplinary team is needed to care for individuals with Fragile X, including specialists in psychiatry, psychology, neurology and genetic counselling.
In certain cases, due to the severity of the condition, caregivers provide extensive support to their loved ones with Fragile X syndrome even for basic daily activities like feeding and bathing.