Spinal Cord Injury
Spinal Cord Injury (SCI) is a devastating condition for which very few medical treatment options exist. The relatively small patient population masks the incredible need for effective drugs.
Cethrin and acute spinal cord injury
We focused on Cethrin as the best investigational candidate because of very positive results in our preclinical studies. Immediately after injury is the most important time to limit damage and start repair. The spinal cord is vulnerable to secondary consequences of injury that include axon degeneration and cell death. Cethrin is the most advanced drug in development for the acute care period the first week after injury. It is applied during surgery, and approximately 90 percent of acute spinal cord injury patients will have surgery to decompress the spinal cord within the first week after SCI.
Cethrin and chronic spinal cord injury
Today there are many other types of treatments in development for neurotrauma, including cell based therapies. Studies in animals suggest that multiple treatments will enhance recovery, but from a translational drug development standpoint, the fastest way to get treatments to patients is to show safety and efficacy for individual therapeutics before experimenting with combinations. Cethrin is collaborating with other researchers to investigate combining Cethrin with cell-based therapies. BioAxone aslo has a discovery program to create new and better drugs.
How Cethrin works:
Cethrin is applied directly to the injured region of the spinal cord during surgery. The drug is deposited in a slow release matrix without injection into the spinal cord, and thus differs from other drugs in development that require risky and invasive delivery methods. Cethrin’s cell penetration sequence enhances the drug’s ability to enter cells and reverse damaging cellular responses by inactivating Rho, one of the master control proteins for axon regeneration.
Strong Proof-of Concept Supports Current Clinical studies
BioAxone evaluated the ability of Cethrin to improve locomotor functional recovery after spinal cord injury in two different animal models. It was found that rats with a contusion SCI recovered more quickly and to a greater extent than vehicle controls. In spinal cord injured mice and rats, a single dose of Cethrin improved locomotor function. Histological observations showed that the treated animals had regenerated axons, more spared tissue, and fewer dying neuron than untreated animals. Further experiments proved that functional recovery was achieved through effective Rho inhibition.
- Cethrin acts on neurons and stimulates damaged axons to regenerate
- Cethrin is neuroprotective and reduces tissue loss after neurotrauma
- Cethrin reduces invasion of damaging macrophages
- Cethrin acts on glial cells to reduce the lesion scar that blocks axon regeneration
Cethrin has been tested in a Phase 1/2a clinical trial designed to test safety and tolerability. The study was a multi-center, dose ranging study in 48 patients with ASIA A complete acute spinal injury, and patient recovery was followed for 12 months. Cethrin had a good safety profile at all of the doses tested. In the cervical patient cohorts, the improvement in ASIA motor score observed at the most effective dose was almost three times the recovery expected in untreated patients. Also, In the cervical patient cohort, 31% of patients treated with Cethrin regained some motor function, compared to 10% expected from historical controls.