Laquinimod (previously known as ABR-215062) is an investigative immunomodulator being developed by Active Biotech and Teva Pharmaceuticals to possibly treat Huntington’s disease. It is also being studied as a treatment for multiple sclerosis (MS).

How laquinimod works

Laquinimod is a quinoline-3-carboxamide derivate (known as ABR-215062) with roquinimex as its main component. It is an orally administered, small molecule that can reach the brain and works to reduce inflammation.

Laquinimod enters the brain, crossing the blood-brain barrier, a natural barrier that protects the brain from many substances circulating in the blood. Preclinical animal studies have shown that laquinimod increases the amount of a substance called brain-derived neurotrophic factor (BDNF) and prevents programmed cell death. BDNF is essential for the survival of nerve cells, and is present at lower than normal levels in patients with Huntington’s.

Laquinimod also reduces inflammation, which is a possible underlying mechanism that causes the death of nerve cells in Huntington’s disease.

Laquinimod in clinical trials

The effects of laquinimod have been investigated in two main studies using a mouse model of Huntington’s disease. Results for both studies showed improvements in movement in the animals, but differences in other outcomes were noted.

One study, with results published in 2017 in the journal Nature, found that laquinimod caused no significant increase in survival times or improvement in weight. However, it did improve motor coordination and balance in older mice. It worked to increase the activity of the gene encoding for BDNF in a region of the brain called the striatum, but not in the motor cortex. Both the striatum and the motor cortex are affected in Huntington’s disease.

The other study, whose results were published in 2016 in the journal Neurology, Neurosurgery & Psychiatry, found that laquinimod improved motor impairment and weight, and extended survival. It found increases in BDNF in the nerve cells of the motor cortex, but not the striatum.

Despite these differences, the treatment’s apparent tolerability and effectiveness justified further testing, as researchers in the 2017 study noted, writing that “laquinimod may be a potential disease-modifying agent for the treatment of HD and other neurodegenerative diseases.”

Laquinimod is currently being investigated in a Phase 2 clinical trial (NCT02215616) in patients with Huntington’s disease. The trial, called LEGATO-HD, is assessing the safety and effectiveness of different doses of laquinimod in 351 patients, ages 21 to 55. Participants are being given either laquinimod (0.5 or 1.0 mg/day) or placebo for a total of 12 months. Testing of a third and higher dose, 1.5 mg daily, in a patient group was stopped in 2016.

The trial, which is no longer recruiting patients, has as its primary outcome measure a change from baseline (study start) in the Unified Huntington’s Disease Rating Scale-Total Motor Scale (UHDRS-TMS), a measure of motor skills and function. It is expected to finish in June 2018.

Other information

Based on clinical trials testing laquinimod in patients with MS, its use at a low dose is considered to be well-tolerated. Higher doses were discontinued in active MS trials due to cardiovascular problems noted in some patients. The reason for stopping the higher dose in the Huntington’s trial was not released.

The most common reported side effects of laquinimod are headaches, back pain, and colds. Some people may also have elevated liver enzyme levels; this side effect was reported to be treatable.

Several clinical trials exploring laquinimod in multiple sclerosis patients treatment are ongoing or have been completed, but the medication is still under investigation and it is not currently approved for use in Huntington’s disease or MS.

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