Science

Restoring neurons and neural circuits lost to neurodegenerative disease

Neurodegenerative diseases are defined by the progressive loss of specific neuron populations and the breakdown of the neural circuits required for normal function. While existing therapies can help manage symptoms, they do not address the underlying neuronal loss that drives disease progression.

Oryon is advancing a neuron replacement technology designed to restore neural circuitry. Unlike symptomatic therapies, this therapeutic approach is intended to produce durable biological restoration in neurodegenerative disorders, in which neuronal loss is well defined and directly linked to clinical impairment. The company’s initial program is in Parkinson’s disease.

Oryon’s program emerged from 30 years of scientific advances in stem cell biology and neurosurgical techniques, including foundational Parkinson’s disease research conducted at Harvard University and Mass General Brigham by Oryon Co-Founder Ole Isacson, M.D., Ph.D., and his team.

Neuron replacement to restore function

Objective imaging shows dopaminergic restoration

Autologous cells, no chronic immunosuppression

Loss of brain circuits in Parkinson’s disease

Parkinson’s disease is characterized by progressive degeneration of dopaminergic neurons located in the midbrain. These cells use the dopamine neurotransmitter to send signals to other neurons. As they degenerate, dopaminergic signaling is lost within the circuits that control motor function, specifically within the putamen region of the brain. This causes people with Parkinson’s to experience worsening motor symptoms, for example slow, stiff movements, lack of facial expression, shuffling gait, and decreased ability to perform ordinary tasks, such as buttoning a shirt, writing or eating with utensils. These functional losses result in increasing dependence on dopamine-replacement medications, and declining functional independence.

Currently, therapy is limited to symptomatic treatments, including medications to increase dopamine in the brain and, in cases where the medicines are no longer effective or cause intractable side effects, surgically implanted electrodes that provide Deep Brain Stimulation. Even with symptomatic therapies, people with Parkinson’s experience progressive loss of function, inability to work or to pursue their hobbies or activities of daily life, and declining functional independence.

Oryon’s autologous cell therapy

Oryon’s therapy is derived from a patient’s own (autologous) blood cells which are reprogrammed to become induced pluripotent stem cells (iPSCs). These cells are able to become any cell in the body, which are then guided to differentiate into the specific type of midbrain dopaminergic neuron affected by Parkinson’s disease. Because the cells are autologous, this approach does not require chronic immunosuppression.

Phase 1/2a clinical trial

Oryon is conducting and ongoing Phase 1/2a clinical study. In the first part of the study autologous dopaminergic neurons were implanted unilaterally into the patient’s post-commissural putamen—the brain region most directly implicated in Parkinson’s motor symptoms. This targeted delivery aims to enable the implanted neurons to reconstitute native neural networks, restoring sustained, physiological dopaminergic signaling.

Objective evidence of dopaminergic restoration

Preclinical studies have shown that Oryon’s implanted dopaminergic neurons result in improved function, associated with evidence of increased dopaminergic activity in the implanted region over time. The Phase 1/2a clinical trial assesses various aspects of the participants’ function and well-being over time, and also uses dopamine transporter imaging (DaT-SPECT), to measure dopaminergic activity in the brain.

In the patients evaluated in the study to date, DaT-SPECT imaging has demonstrated increases in dopaminergic signaling within the implanted brain regions, while non-implanted regions have not shown comparable changes.

The next cohort of trial participants will receive bilateral autologous dopaminergic neuron implants.