In a new laboratory study from Italy, investigators have reported a very exciting result for Huntington's (HD). Pridopidine, the drug presently in clinical trial for HD was shown -- not just to treat motor symptoms -- but also to provide neuroprotective benefit in a genetic mouse model of Huntington's.

Though the important pridopidine human study, the PRIDE-HD trial has another year to be completed, and more time needed to complete analysis, this mouse study suggests we might get more than symptom benefit from this new drug. Exciting indeed that it might give neuroprotection too.

The Mouse Study

Motor benefit: Squitieri and colleagues from Italy [Squitieri F 2015] showed that giving pridopidine to mice at a time just before usual onset of motor symptoms greatly improved subseqent motor behavior and coordination until fairly late in the usual life-span of the R62 mouse. They then found that giving a larger dose of the drug at this later stage gave a longer time of motor benefit. This larger dose had too many side effects in the early stage mice. They showed -- at least in this mouse model -- that "best" dose of this drug for treating motor symptoms depends on the stage of disease.

Neuroprotective benefit: The investigators showed that pridopidine treated R62 mice lived longer and that mutant huntingtin aggregates were smaller in the drug treated mice. Both of these findings suggest a neuroprotective effect. Though brain weights trended greater in the treated group, the difference was not significant. The authors go further to show that protective neurochemicals (BDNF and DARPP32) are higher in the drug treated mice.

The Human Studies

Two earlier clinical trials in North America and Europe showed improved overall motor function at a 45 mg twice daily dose. The present international PRIDE-HD trial is testing a range of doses up to 112.5 mg twice daily. Though this study is designed to test for motor symptom benefit, the one-year duration of this trial may give a hint of a signal for neuroprotection, though it is unlikely to be definitive.

The "Drugs for HD" Heroes We can hope that the PRIDE trial will be successful. But whether successful or not there is a long list of heroes in the pridopidine story. Avrid Carlsson, a Nobel prize-winning neuroscientist was first to study and develop drugs similar to pridopidine. In 1999 one of these drugs was tried, with reported benefit in a first individual with advanced HD [Tedroff J 1999]. Rights to that drug were then bought by a large drug company who chose not to develop it further for HD. Dr. Carlsson then developed a similar drug (ACR-16) specifying that it must used in HD. Rights to ACR-16/pridopidine then went to NeuroSearch, a small biotech company who sponsored the two earlier large clinical trials in HD. And finally, TEVA, a large pharmaceutical company with Michael Hayden leading the HD effort is sponsoring PRIDE. And there are so many more heroes; A legion of hundreds of laboratory scientists, HD clinicians investigators and coordinators around the world.

The HD Medical Heroes (past, present and future): And finally there are the hundreds and thousands of unsung medical hero participants and families across the world who give selflessly, and put themselves at unknown risk to be in this and other clinical trials and studies. They do this for the benefit of us all. PRIDE is nearing complete enrollment, but to complete this HD drug story, and others that are sure to follow, we all need to take that courageous step to become an HD medical hero.

References

Squitieri F, Di Pardo A, Favellato M, Amico E, Maglione V, Frati L. Pridopidine, a dopamine stabilizer, improves motor performance and shows neuroprotective effects in Huntington disease R6/2 mouse model. J Cell Mol Med. 2015 Nov;19(11):2540-8. doi: 10.1111/jcmm.12604. Epub 2015 Jun 22. PubMed abstract

Tedroff J, Ekesbo A, Sonesson C, Waters N, Carlsson A. Long-lasting improvement following (-)-OSU6162 in a patient with Huntington's disease. Neurology. 1999 Oct 22;53(7):1605-6. PubMed abstract