Tolerability of SRX246 in Huntington's Disease Patients

DESCRIPTIONprovided by applicantHuntington s DiseaseHDis an inherited disease that results from expansion of a trinucleotideCAGcytosine adenine guaninerepeat that encodes a polyglutamine tract in the huntingtin proteinPsychiatric symptomsincluding irritability and aggressionare common in HD patientsThese are among the most distressing aspects of the diseaseThey have adverse effects on daily life and often result in institutionalizationDespite the frequent occurrence and severe consequences of irritability and aggression in HDthese symptoms have received little attention to dateEffective treatments are lacking and well validated scales for measuring changes in these symptoms are not availableFaced with a significant unmet needneurologists cannot currently determine whether new drug therapies might be useful in treating neuropsychiatric symptoms in HDThe Phase II clinical trial we propose in HD patientsn" A randomizedplacebo controlleddouble blindmulti center study to assess the tolerability of SRXin irritable aggressive subjects wit Huntington s DiseaseHD" will allow us to rigorously evaluate the tolerability of a potential ne drug for the treatment of irritability and aggressionIt will also provide additional safety data n the compound and explore various rating scales for the assessment of changes in these symptomsThuswe will obtain critical data that can be used to plan future Phase II or III clinicl trials of drugs that might blunt irritability and aggression in HDThe compound that we propose to test is SRXa first in class vasopressinaV areceptor antagonistSRXcrosses the blood brain barrier following oral administrationexhibits high affinity and selectivity for is target receptorhas a strong safety profileis well tolerated in healthy volunteersand has excellent pharmacokineticsExtensive preclinical pharmacology studies and an experimental medicine fMRI study in healthy volunteers have shown that SRXhas CNS effects after oral administration and that it modulates brain circuits involved in responses to stimuli that elicit aggression fearThese findings strongly suggest that SRXmight have a beneficial effect on the irritability and aggression seen in a sizable proportion of HD patientsThe proposed project will generate data needed to plan a future clinical trial that can rigorously test SRXfor efficacy as a treatment for irritability and aggression