Laquinimod, Potential PPMS Therapy, Seen to Ease Damage to Vision in Mouse Model
Treating mice in a model of multiple sclerosis (MS) with laquinimod before the onset of symptoms eased inflammation so as to help preserve their vision — lessening damage to the optic nerve and retina, a study from Germany reports.
The study, “Laquinimod protects the optic nerve and retina in an experimental autoimmune encephalomyelitis model” was published in the Journal of Neuroinflammation.
In 30 percent of MS patients, eye diseases such as optic neuritis — inflammation of the optic nerve — is often a first symptom. As the disease progresses, 60–70 percent of these patients show some form of eye damage.
Laquinimod is an experimental immunomodulator — an agent that changes the behavior of immune cells of the central nervous system — being developed by Teva Pharmaceuticals and Active Biotech as a potential treatment for primary progressive MS and Huntington’s disease.
Far less is known about its anti-inflammatory effects on patients’ vision.
Researchers at the Ruhr-University Bochum investigated the therapeutic effect of laquinimod on the visual system — the optic nerve and retina — in an MS mouse model known as experimental autoimmune encephalomyelitis (EAE). (The retina is the layer of nerve cells lining the back of the eye; it senses light and sends signals to the brain.)
The mice were given either 1, 5, or 25 mg/kg of laquinimod orally each day for 29 days, starting with the day they were induced to develop MS (becoming EAE model mice, but asymptomatic). Researchers compared results of treated EAE mice with those of untreated EAE mice, and a healthy control group on day 30.
The team also tested laquinimod as a therapy in diagnosed patients, treating five diseased mice with 25 mg/kg of laquinimod daily beginning on day 16, when MS-like symptoms were evident.
Results showed that laquinimod given early eased inflammation of the retina and lessened optic nerve demyelination in treated EAE mice relative to untreated mice.
Microglia — a main form of active immune defense of the central nervous system in healthy people but a source of inflammation and neurotoxic processes in MS patients — were also affected by treatment. The number of microglia in the retina was significantly lower in treated mice at all three laquinimod doses used. But mice treated at the high dose, 25 mg/kg, showed the most significant benefits (87.4 cells per mm2) compared with untreated mice (393.2 cells per mm2).
Loss of the protective myelin sheath (demyelination) along the optic nerve is the hallmark of optic neuritis and was also examined. Researchers found that, compared with untreated EAE mice, those given 25 mg/kg of laquinimod daily had lesser optic nerve demyelination.
Ganglion cells are a type of nerve cell found on the inner surface of the retina, and their loss has been reported in EAE mice. Researchers reported that treatment with 5 and 25 mg/kg of laquinimod daily — but not the lowest dose — prevented ganglion cell death and increased their numbers in EAE mice.
Likewise, mice treated after the onset of MS symptoms showed improvements in vision and partly restored retinal function, but no protective effect was found regarding optic nerve demyelination.
The researchers concluded that laquinimod worked to ease neurological symptoms in EAE mice, so as to preserve vision. When given early in the disease course, it prevented inflammation and degeneration of the visual system in EAE mice.
“From our study, we deduce neuroprotective and anti-inflammatory effects of laquinimod on the optic nerve and retina in EAE mice, when animals were treated before any clinical signs were noted,” they wrote. “Given the fact that the visual system is frequently affected by MS, the agent might be an interesting subject of further neuro-ophthalmic investigations.”