People often equate seizures with convulsions, but in reality, seizures are any abnormal, uncontrollable firing of neural networks within the brain. As a result, seizures can impact any function controlled by the brain, and so they can take on many forms - not just convulsions. Because epilepsy doesn’t always come with dramatic and obvious seizures, it is much more widespread than most people would assume, and much more difficult to treat.
Epilepsy affects approximately 50 million people worldwide. Around 30% of those patients routinely have seizures that are not adequately treated by current medical therapy. While there are many types and causes of epilepsy, they all ultimately result from an imbalance of excitory and inhibitory brain-cell function. Restoring this balance can reduce or eliminate seizures, bringing epilepsy under control. While current medications manage some types of epilepsy effectively, other types are highly resistant to therapy (i.e. they are refractory). In addition, many patients feel lethargic and sleepy while taking their medication due to the sedative nature of these drugs.
NeuroCycle Therapeutics plans to evaluate its non-sedating compounds in models of rare and severe forms of pediatric epilepsy that are refractory to treatment.
NeP has a significant, negative impact on patients’ quality of life. In fact, more than 35% of patients with neuropathic pain develop depression or anxiety. At best, only 15-25% of patients achieve a 50% reduction of symptoms with current first-line therapies - and side effects are common. The other 75-85% of patients often receive little to no benefit from therapy, and they are left struggling to find an effective treatment regimen.
It is clear that patients suffering from NeP need new, effective therapies with fewer side effects.
While there are many forms and origins of NeP, the three most commonly studied subtypes are diabetic neuropathic pain (DNP), postherpetic neuralgia (PHN), and HIV-related neuropathic pain. Together, these three subtypes afflicted over 6 million patients across the United States, Japan, and Western Europe in 2010. Estimates predict the U.S. market for NeP drugs will reach nearly $3.6 billion by 2020.
Standard of Care: Risks and Limitations
Current first-line therapies include tricyclic antidepressants (e.g. amitriptyline), serotonin and norepinephrine reuptake inhibitors (e.g. duloxetine), and antiepileptics (e.g. gabapentin and pregabalin). Side effects are common with these treatments and include drowsiness, dizziness, nausea, and adverse anticholinergic effects in the case of tricyclic antidepressants. Often, doctors must customize treatment plans to find one that is both efficacious and tolerable.
Second-line therapies typically include opioids and topical drugs (e.g. lidocaine, capsaicin). Opioids are effective in acute management of NeP. However, a systematic review of randomized trials found the evidence of benefit over three months “was poor based on either weak positive evidence or indeterminate or negative evidence.” (Christo, P.J. et al. Pain Physician 2011).
In addition to the significant abuse potential of opioids, they are also associated with increased bone fracture, hospitalization, and mortality which limits their usefulness - especially for the elderly. Although topical therapies may be efficacious in some patients, the therapeutic gain is usually only slightly greater than the placebo.