Neurology
Trigeminal Neuralgia
Trigeminal Neuralgia is a devastating disorder characterized by frequent, debilitating, and recurrent paroxysmal pain attacks. Trigeminal Neuralgia affects the trigeminal nerve, the fifth cranial nerve that innervates the face, causing severe, “electric shock-like” facial pain.
Trigeminal Neuralgia affects approximately 400,000 people in the United States and European Union.
Current treatments include anticonvulsants, which can have significant tolerability issues and waning efficacy over time. Medically-refractory patients may be candidates for neurosurgical interventions, which are invasive and carry significant risks.
Kriya is developing KRIYA‑748, a potential one-time gene therapy for trigeminal neuralgia that expresses a chemogenetically-gated ion channel and is designed to be administered as an injection into the trigeminal nerve, with the objective of reducing the frequency and severity of pain attacks. Once expressed in the nerve, this channel is designed to selectively open in the presence of varenicline, an orally-administered small molecule that penetrates the central nervous system (CNS), leading to the passage of chloride ions and reduced excitation of target neurons. Varenicline is an FDA-approved generic medication for smoking cessation, originally marketed under the brand name “Chantix®”.
Kriya has designed KRIYA‑748 for trigeminal neuralgia with the following potential goals in mind:
- Pain reduction. Reducing the frequency and severity of pain attacks by focally inhibiting neuronal hyperexcitability in the trigeminal nerve
- Long-term durability. One-time administration of gene therapy to eliminate the need for cycling through anti-epileptic medications and surgical procedures
- Regulatable activity. Targeted delivery to the trigeminal nerve, additionally engineered with the ability to “turn off” the gene therapy through withdrawal of the orally-administered small molecule, varenicline
Approach to Treating Trigeminal Neuralgia with Gene Therapy
There is strong experimental evidence that neurons and associated behavioral networks are shaped by the interactions of ion channels expressed in specific neuronal groups. Kriya’s adeno-associated virus (AAV) gene therapy is designed to durably express an engineered ion channel focally within the trigeminal nerve, which may provide targeted pain relief. Preclinical studies have demonstrated that this ion channel is selectively opened in the presence of varenicline, an orally-administered and CNS-penetrant small molecule, leading to the passage of chloride ions and reduced excitation of target neurons. Kriya believes that this approach to treating trigeminal neuralgia may provide targeted and durable pain control – compared to anticonvulsants that may wane in efficacy over time or invasive neurosurgical interventions that carry procedural risks.
Ophthalmology
Metabolic
Neurology