Laquinimod Reduces Signs of Inflammation, Brain Atrophy in Huntington’s, Data Show

Laquinimod Reduces Signs of Inflammation, Brain Atrophy in  Huntington’s, Data Show

Laquinimod, an experimental immunomodulatory therapy developed by Active Biotech and Teva Pharmaceuticals, reduced signs of inflammation and brain atrophy (shrinkage) in patients with Huntington’s disease, data from an exploratory analysis of a Phase 2 trial show.

The new data were presented by Active Biotech in three posters during the International Congress of Parkinson’s disease and Movement disorders, held Sept. 22–26 in Nice, France.

Laquinimod is an oral immunomodulatory medicine that is able to cross the blood-brain barrier, which protects the brain from harmful substances carried in the blood, and change immune cells’ behavior to reduce inflammation and prevent neurodegeneration in the central nervous system (CNS, composed of the brain and spinal cord).

Previous studies in mice models have shown that laquinimod can regulate brain-related inflammatory pathways involved in the underlying mechanisms of Huntington’s disease.

The randomized, double-blind, placebo-controlled, Phase 2 LEGATO-HD study (NCT02215616) has been designed to assess the safety and efficacy of laquinimod for the treatment of patients with Huntington’s disease.

In the trial, patients were randomly assigned to receive either laquinimod, at a dose of 0.5, 1.0, or 1.5 mg, or a placebo, administered once a day for a year.

The trial’s primary outcome was to assess changes in patients’ motor function from baseline to a year after treatment, as determined by the Unified Huntington’s Disease Rating Scale Total Motor Score (UHDRS-TMS). Secondary outcomes included assessing the effects of laquinimod on brain atrophy.

Although the primary outcome of the trial was not met and laquinimod failed to improve patients’ motor function after one year of treatment, Active Biotech presented promising findings from an exploratory analysis of LEGATO-HD at the congress.

In a poster titled, “Magnetic Resonance Spectroscopy Evaluation of Neuronal Integrity and Astrocytosis in a Phase 2 study of Laquinimod as a Treatment for Huntington Disease (LEGATO-HD),” the company announced the findings of a sub-study of LEGATO-HD focused on assessing the effects of laquinimod on brain inflammation.

Results showed that laquinimod significantly reduced levels of myo-inositol, a marker of astrocytes (star-shaped nerve cells thought to provide support to neurons), compared to a placebo, in the putamen (a brain region involved in learning and movement control) of patients with early Huntington’s disease.

“[These findings] suggest that laquinimod treatment decreases astrocytosis and gliosis [two processes that normally occur in response to neuron damage and inflammation], consistent with its known in vitro and in vivo effects on neuroinflammation,” the poster stated.

In a second poster titled, “Brain MRI Volume Changes after 12 months laquinimod treatment of Huntington disease (LEGATO-HD),” the company presented the findings of a secondary outcome of LEGATO-HD focused on assessing the effects of laquinimod on brain atrophy.

Findings revealed that over one year of treatment, laquinimod significantly reduced volume loss in several regions of the brain compared to a placebo, successfully meeting the secondary outcome of minimizing volume changes in the caudate nucleus (a brain region involved in learning, memory, and movement control).

However, “[t]he reduction of brain volume loss in the laquinimod groups did not correlate with improvements in the primary endpoint, UHDRS-Total Motor Score (UHDRS-TMS), and other clinical outcomes,” the researchers stated.

In another poster titled, “Quantitative Motor (Q-Motor) Assessments Suggest a Beneficial Central Effect of Laquinimod in a Phase II Study in Huntington Disease (LEGATO-HD),” the company presented the findings of an exploratory outcome of LEGATO-HD focused on assessing the effects of laquinimod on quantitative motor (Q-Motor) measures that included evaluating the speed of finger and hand tapping and grip strength, among others.

Patients who had been treated with laquinimod at a dose of 0.5 mg had significant improvements in Q-Motor measures after one year of treatment, compared to a placebo. Patients who were treated with laquinimod at a dose of 1.0 mg also showed positive trends in several parameters analyzed by the Q-Motor measures.

“The results of the Q-Motor assessment must be viewed cautiously as corrections for multiplicity were not performed on these analyses, however these observations suggest a central beneficial effect of laquinimod in LEGATO-HD of unknown clinical significance and support a biological relevance of the imaging changes observed,” the researchers noted.

Joana is currently completing her PhD in Biomedicine and Clinical Research at Universidade de Lisboa. She also holds a BSc in Biology and an MSc in Evolutionary and Developmental Biology from Universidade de Lisboa. Her work has been focused on the impact of non-canonical Wnt signaling in the collective behavior of endothelial cells — cells that make up the lining of blood vessels — found in the umbilical cord of newborns.
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Ana holds a PhD in Immunology from the University of Lisbon and worked as a postdoctoral researcher at Instituto de Medicina Molecular (iMM) in Lisbon, Portugal. She graduated with a BSc in Genetics from the University of Newcastle and received a Masters in Biomolecular Archaeology from the University of Manchester, England. After leaving the lab to pursue a career in Science Communication, she served as the Director of Science Communication at iMM.
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Joana is currently completing her PhD in Biomedicine and Clinical Research at Universidade de Lisboa. She also holds a BSc in Biology and an MSc in Evolutionary and Developmental Biology from Universidade de Lisboa. Her work has been focused on the impact of non-canonical Wnt signaling in the collective behavior of endothelial cells — cells that make up the lining of blood vessels — found in the umbilical cord of newborns.
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3 comments

  1. L Lindsay says:

    I read each week studies
    of this and studies of that with
    HD. So many researchers but
    yet no one can come up with
    A treatment. At this rate our
    love ones will be gone.
    It’s been 25 yrs! Will it be
    25 more years?
    Someone has to come up with
    A treatment and soon.

  2. Karen Johnson says:

    This is great news, my daughter was in the legato study and I feel she was on laquinamod and seemed to improve while in the study. When the study ended I could see I rapid decline in her Huntington’s symptoms. Do you know what if further studies will be conducted for Huntington’s patients? Can she get the drug now?
    Thank you for any help,
    Karen Johnson

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