Both GABA and NMDA systems contribute significantly to regulating CNS function. However, dysfunction in these two systems is known to be at the core of numerous neurological disorders. Navigating these complex circuits is a challenge, but a welcome opportunity for the teams at Sage as we seek to provide new treatments for patients.
We are using our unique development approach to systemically evaluate our drug candidates in a range of neurological, neurodegenerative, and neurodevelopment disorders:
Dementia, including Alzheimer’s disease and a broad spectrum of other forms, affects more than 36 million people worldwide. This neurodegenerative disorder is characterized by a decline in cognitive function. Evidence suggests that enhancing the excitatory NMDA pathway in the brain could work to treat several kinds of dementia. Researchers have found elevated anti-NMDA antibodies in many people with dementia.
Epilepsy is a group of neurological disorders characterized by recurrent seizures (a sudden surge of electrical activity in the brain). Despite there being more than 25 approved therapies for epilepsy, about 30% of patients still suffer from refractory (resistant to treatment) seizures. Imbalance with the inhibitory and excitatory pathways in the brain contributes to the frequency and length of seizures. We’re exploring how enhancing GABA or NMDA signaling could potentially help these patients.
Essential tremor is the most common movement disorder − 8 times more prevalent than Parkinson’s disease. It is a progressive, often inherited, condition that causes rhythmic trembling of the hands, head, voice, or legs. Researchers think it may be caused by electrical fluctuations in the brain that send abnormal signals out to the muscles. For millions of people, essential tremor makes the simplest activities of daily life difficult, if not impossible. Tremors usually worsen with stress, fatigue and stimulant use. Essential tremor has been associated with reduction in GABA receptor activity.
Parkinson’s disease is a chronic and progressive movement disorder that affects approximately 700,000 people in the U.S. In this disease, nerve cells in the brain slowly stop producing dopamine, the neurotransmitter responsible for coordinating movement. As Parkinson’s disease progresses, dopamine produced in the brain decreases, leaving patients less able to direct their movement. Parkinson’s disease may cause tremors, stiffness, slow movement and balance trouble, as well as mood changes and sleep difficulties. Current treatments for Parkinson’s disease focus on dopamine replacement, and are effective in reducing symptoms initially, but lose effectiveness over time.
GABA receptors may be a possible therapeutic target in the treatment of Parkinson’s disease. GABA signaling is known to help regulate the nerve cells that produce dopamine. Researchers have also found decreased levels of allopregnanolone, a naturally-occurring GABA modulator, in patients with Parkinson’s disease.