In a recent New York Times article, Dr. Siddhartha Mukherjee, a cancer expert from Columbia University wisely recommended that potential clinical trial participants ask their investigators "Why is the trial being done?" And "What were the data that led to the clinical trial in the first place?"

So, what about LEGATO and laquinimod? What are the data that led to this drug being tested in HD?

What is Laqunimod? Laquinimod is an experimental drug from TEVA Pharmaceuticals that has already been tested in previous clinical trials in several diseases including Multiple Sclerosis (MS). This drug is thought to affect (or modulate) immune activity by shifting an injurious inflammatory situation to one that is more protective and anti-inflammatory. There is also evidence from various clinical trials that laquinimod may delay progression of disability in MS, and that it reduces brain atrophy as measured by MRI brain scans. By reducing brain atrophy, this drug may have neuroprotective effects [Varrin-Doyer M 2014]. This drug can trigger protective neuron factors like BDNF (as measured in blood of MS clinical trial participants) that supports the health of neurons.

Why a Laquinimod Clinical Trial in HD? It is thought this type of drug may be helpful because inflammation is thought to be one of the key destructive factors in HD. Further, if this drug can increase levels of neuroprotective factors like BDNF, this may be beneficial in HD as well. While the endpoints being measured in this trial are related to motor symptoms, and hoped for improvements will be used for purposes of the FDA, investigators will be looking for a neuroprotective signal as well. That's why this trial includes MRI brain scans at the beginning and end of this 1 year long trial.

There are no studies (that this author could find) regarding testing of laquimimod in cell or mouse models of HD, but one reported on fingolamod, a similar drug [Di Pardo A 2014] where neuroprotective effects were described.

Author's Comments Dr. Siddhartha Mukherjee suggestions about what our patient and family community should be asking about drugs coming to clinical trials, re "Why is the trial being done?" And "What were the data that led to the clinical trial in the first place?" is vital. This is particularly important as our clinical trials become more complicated, and several are recruiting concurrently. This information should be provided to the community in a format that is easily assessable and in language that potential participants can understand for every new trial. Can sponsors or investigators expect participants to sign up when rationale for testing the drug isn't more available?


Varrin-Doyer M, Zamvil SS, Schulze-Topphoff U. Laquinimod, an up-and-coming immunomodulatory agent for treatment of multiple sclerosis. Exp Neurol. 2014 Dec;262 Pt A:66-71. doi: 10.1016/j.expneurol.2014.04.002. Epub 2014 Apr 13. PubMed abstract

Di Pardo A, Amico E, Favellato M, Castrataro R, Fucile S, Squitieri F, Maglione V. FTY720 (fingolimod) is a neuroprotective and disease-modifying agent in cellular and mouse models of Huntington disease. Hum Mol Genet. 2014 May 1;23(9):2251-65. doi: 10.1093/hmg/ddt615. Epub 2013 Dec 2. PubMed abstract