Clinical trial NCT02197104
Conditions: Fragile X Tremor/Ataxia Syndrome
Sponsor: Rush University Medical Center
Start date: 2015-01-01; Completion date: 2017-01-01
Enrollment: 10 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
The objective of this study is to determine if citocoline is effective for balance abnormalities and to stabilize cognitive decline in patients with fragile X-associated tremor ataxia syndrome. The study will test 1000mg twice daily of citocoline for 12 months in an open label pilot study, with study visits at baseline, 3, 6, and 12 months.

Detailed description:
The purpose of this study was to determine if citicoline was safe for the treatment of tremor and balance abnormalities and to stabilize cognitive decline in patients with fragile X-associated tremor ataxia syndrome. Ten participants with diagnosed FXTAS were administered 1000 mg of citicoline once daily for 12 months. Outcome measures and neurological examination were performed at baseline, 3 months, 6 months, and 12 months. The primary outcome was safety. Secondary outcomes included change in FXTAS Rating Scale score, a battery of neuropsychological tests, an instrumented Timed up and go test, computerized dynamic posturography, 9-hole pegboard test, and balance confidence and psychiatric symptom questionnaires.

Arms: arm 1: The intervention will be 1000mg of citicoline in capsule form once daily.
Interventions: intervention 1: citocoline
Intervention descriptions: intervention 1: Ten subjects will receive 1,000mg once daily of citicoline. Each subject will stay on the study drug for 12 months. The outcome measures will be assessed at baseline and then again at the end of month 3, month 6, and month 12. The subjects will continue taking the same study drug at the same dose throughout the entire trial.

Protocol documents:
Prot_SAP_000.pdf: 
PROTOCOL 
 
Principal Investigator:  
Deborah A. Hall, MD PhD 
Version date:  
 
1/12/2015 
Study Title 
Citicoline for neurological signs in fragile X-associated tremor/ataxia syndrome 
(FXTAS) 
 
Objectives 
The objective of this study is to determine if citicoline is effective for balance 
abnormalities and to stabilize cognitive decline in patients with FXTAS.   
 
Design and Outcomes 
The design of this study is an open label study conducted at one center.  The primary 
outcome is change in the FXTAS Rating Scale (FXTAS-RS).  Secondary outcome 
measures include neuropsychological tests (Behavioral Dyscontrol Scale, Stroop, WAIS 
PIQ, WASI, Animal Naming, Purdue Pegboard, Digits Backwards, Symbol Digits, and 
COWAT), instrumented Timed up and go (iTUG) test, Computed Dynamic 
Posturography (CDP), Activities-specific balance confidence (ABC) scale, Beck Anxiety 
Inventory (BAI), and Center for Epidemiological Studies Depression Scale Revised 
(CESD-R). 
 
Interventions and Duration 
The intervention will be 1000mg of citicoline once daily.  Outcome measures and 
neurological examination will be performed at baseline, 3 months, 6 months, and 12 
months.   
 
Sample size and population 
Sample size for the initial pilot study is ten patients.  All patients will meet critieria for 
possible, probable, or definite FXTAS per the Jacquemont et al diagnostic criteria 
(Jacquemont, 2003).  There will be no stratification or randomization.       
 
STUDY OBJECTIVES 
 
Primary Objective 
 
The hypothesis tested is that citicoline will result in improvement of scores on the 
FXTAS Rating Scale after 12 months of treatment.  The null hypothesis is that there will 
be no difference between baseline and final outcome measures on the FXTAS Rating 
Scale.  This scale will be performed by the principal investigator, a movement disorder 
neurologist involved in the development of this scale.    
  
Secondary Objectives 


 
There are two secondary hypotheses.  First, we hypothesize that subjects will have 
stabilization of cognitive decline on citicoline.  This hypothesis will be tested by 
measuring scores on the following neuropsychological tests: Behavioral Dyscontrol 
Scale, Stroop, WAIS PIQ, WASI, Animal Naming, Purdue Pegboard, Digits Backwards, 
Symbol Digits, and COWAT.  Second, we hypothesize that patients will improve on 
Computed Dynamic Posturography and the instrumented Timed up and go test.  The 
secondary outcomes will be performed by the study team and led by the site investigator.  
  
BACKGROUND 
 
Rationale 
Fragile X-associated tremor/ ataxia syndrome (FXTAS) is characterized by tremor, 
cerebellar ataxia, frequent falls, cognitive decline and progressive loss of motor function.  
It is a newly recognized, late onset neurodegenerative disorder that occurs in carriers of a 
premutation in the fragile X mental retardation 1 (FMR1) gene located on the X 
chromosome.  There are approximately 785,000 female and 314,000 male FMR1 
premutation carriers in the US and roughly 75% of men and 15% of women carriers will 
develop FXTAS in their lifetime.  There are currently no targeted therapeutic treatments 
for FXTAS.  However, there are promising pharmaceutical treatment approaches with 
potential symptomatic benefits based on their effectiveness in treating disorders that have 
significant phenotypic overlap with FXTAS.  
 
Citicoline is an endogenous nucleotide and intermediate in the biosynthesis of structural 
membrane phospholipids and has been shown in initial studies to be effective in treating 
neurodegenerative disorders associated with head trauma, stroke, brain aging, 
cerebrovascular pathology and Alzheimer disease (Alvarez, 1999).  FXTAS occurs in 
some carriers of a premutation size expansion (55-200 CGG repeats) in the promoter 
region of the FMR1 gene.  Increased CGG repeat length leads to increased FMR1 mRNA, 
which is implicated in the neuronal toxicity causing motor and cognitive dysfunction in 
FXTAS.  In a FXTAS Drosophila model, citicoline demonstrated the ability to reduce 
neuronal toxicity caused by CGG repeat FMR1 mRNA by decreasing locomotion deficits 
and lethality (Qurashi, 2012).  Citicoline also improved cognitive performance in patients 
with Alzheimer disease and mild dementia when given at 1,000 mg per day (Alvarez, 
1999).  Currently there are no FDA approved medications for treatment of the motor and 
cognitive dysfunction in FXTAS patients 
 
The study drug regimen in this protocol is similar to those studies conducted for 
Alzheimer disease and stroke.  The active study drug will be dosed once daily due to 
convention.  There are no aspects of the proposed dosing schedule that are not FDA-
approved for other indications.  This study is of high priority due to the absence of any 
proven medications to treat the symptoms of this disorder.  
 
STUDY DESIGN 
This is an open label designed study.  Citicoline was chosen because of its novel 
mechanism of action and its preliminary success in treating some forms of neurological 


disease.  This will be the first clinical trial testing citicoline in patients with FXTAS.  
Citicoline has demonstrated the ability to mediate neuronal toxicity presumably via its 
inhibition of phospholipase A2.  This action of phospholipase A2 inhibition may provide a 
mechanism to mitigate locomotion and cognitive deficits in this patient population.   
 
SELECTION AND ENROLLMENT OF SUBJECTS 
 
Inclusion criteria: 
• Subjects will be diagnosed with Fragile X-associated tremor/ataxia syndrome 
(FXTAS) by the Jacquemont et al diagnostic criteria (see Table 1).   
• Serum creatine kinase, complete metabolic panel, complete blood count, liver 
function tests, renal function tests, platelets and EKG are within normal limits 
(results obtained from primary care physician and dated within the past 6 months 
or obtained at screening visit).   
• Older than age 18.   
Exclusion criteria: 
• Patient refuses to assent or no LAR if cognitively impaired  
• Presence of severe renal disease (BUN 50% greater than normal or creatinine 
clearance <60 mL/min) or hepatic disease. 
• Abnormal creatine kinase and/or platelet count in the past 6 months (as 
determined by lab reports obtained from primary care physicians or conducted at 
baseline). 
• Women of childbearing potential who are pregnant at the time of screening or 
who will not use adequate protection during participation of the study.  
• Allergy/sensitivity to the citicoline or its formulations. 
• Concurrent participation in another clinical study. 
• Active substance use or dependence. 
• Serious illness (requiring systematic treatment/or hospitalization) until the subject 
either completes therapy or is clinically stable on therapy, in the opinion of the 
site investigator, for at least 60 days prior to study entry.  
 
Table 1: Diagnostic criteria for FXTAS (adapted from Jacquemont et al, 2003) 
 
 
Molecular 
 
FMR1 CGG Repeat Size 55-200 
 
Clinical 
Major signs:  
Intention tremor 
 
 
 
Gait ataxia 
Minor signs:  
Parkinsonism 
 
 
 
Moderate to severe short term memory deficits 
 
 
 
Executive function deficits 
 
Radiological 
Major signs:  
MRI white matter lesions in the middle cerebellar peduncle (MCP 
sign) 


Minor signs:  
MRI white matter lesions in cerebral white matter 
 
 
 
Moderate to severe generalized atrophy 
 
Diagnostic Categories 
Definite: 
Presence of one major radiological sign plus one major clinical symptom 
Probable: 
Presence of either one major radiological sign plus one minor clinical 
symptom or  
 
 
has two major clinical symptoms 
Possible: 
Presence of one minor radiological sign plus one major clinical symptom 
 
Study Enrollment Procedures 
Patients with Fragile X-associated tremor/ataxia syndrome (FXTAS) will be recruited 
through the Parkinson Disease and Movement Disorder clinic at Rush University Medical 
Center.  There are nine movement disorder attending physicians and two fellows who see 
about 25 FXTAS patients a year as new patients and in follow up.  Recruitment goals are 
expected to be predominantly achieved through the cohort of individuals seen at Rush, 
but advertising may also be conducted through monthly FXTAS meetings to enhance 
enrollment.  Potential subjects may be identified by their treating physician in the 
Movement Disorders Clinic at Rush or referred to Rush from elsewhere.  If a patient is 
interested in enrolling in the study, they will be invited to an initial study visit, at which 
they will sign informed consent after a full explanation of the study.   
 
Documentation of inclusion and exclusion criteria will occur if the patient is 
interested in enrollment.  Eligible subjects who refuse participation will be given the 
option of later enrollment if they should choose to join the study. 
 
Much of recruitment will occur from physicians with a treatment relationship with 
the patient.  Consent will occur between the primary investigator on the study and the 
potential subject.  All investigators are trained in the conduct of human research.  The 
patient will have a mini mental state examination (MMSE) performed to determine level 
of understanding prior to the consent process.  If the potential subject scores less than 25, 
the patient will not be allowed to gain entry into the study.  A copy of the consent form 
will be provided to all subjects. 
 
STUDY INTERVENTIONS 
 
Interventions, Administration, and Duration 
Ten subjects will receive 1,000mg once daily of citicoline.  Each subject will stay on the 
study drug for 12 months.  The outcome measures will be assessed at baseline and then 
again at the end of month 3, month 6, and month 12.  The subjects will continue taking 
the same study drug at the same dose throughout the entire trial.  There are no expected 
side effects, however, adverse events will be monitored throughout the study.  Subjects 
will be seen and treated in the outpatient Movement Disorders Clinic at Rush.  Subjects 
will come to the clinic for 6 in person visits and 3 telephone visits will be conducted.   All 
patients may remain on other medications for neurologic signs, but the dose of these 
medications needs to remain stable during the 12 months of the study.     
 
The Handling of Study Interventions 


The study drug will be manufactured by Jarrow Formulas and purchased from the online 
retailer ProVitaminas in the form of 250mg capsules.  The study drug will then be 
shipped to the Principal Investigator at Rush.  The study drug will be dispensed by the 
study team at Rush who will dispense the study drug to the subjects.  The study drug will 
be stored at room temperature in the Parkinson Disease and Movement Disorder clinic 
which will be secured by lock.  The study drug will be provided to the subjects in pill 
bottles.  They will receive four capsules of 250mg daily for the 12 months of 
intervention.  Subjects should take four capsules once a day at mealtime, or two capsules 
twice a day at mealtime if they are having upset stomach.  Subjects will be asked to 
return any unused study drug after 12 months to Rush.  Study intervention accountability 
records will be completed according to the Manual of Operations.  
 
Concomitant Interventions 
Medications for neurological signs of Fragile X-associated tremor/ataxia syndrome need 
to be stable during the 12 months of this study.  There are no contraindicated 
interventions.  
• Required Interventions: citicoline 1,000mg once daily. 
• Prohibited Interventions: none.  
 
Adherence Assessment 
Adherence will be assessed by pill counts and adherence questionnaires that will be 
completed at each of the study visits.  Because the study is using an intent to treat 
analysis, adherence will be reported using descriptive statistics.   
 
CLINICAL AND LABORATORY EVALUATIONS 
 
Timing of Evaluations 
Subjects will be consented and have initial laboratory studies and rating scales at the 
baseline  visit.  Once on the study drug, they will be contacted by phone at Week 3 for 
questions regarding side effects, clinical issues, and to answer any questions.  The 
subjects will be reassessed after six weeks for anxiety and depression, and they will 
continue with the intervention.  Again, they will be contacted by phone at Week 9 and 
Month 9 to assess for safety and tolerability.  They will be seen in the clinic at Month 3, 
Month 6 and Month 12and outcome measures will be performed.   
 
Table 2 
Evaluation 
 
Screening Baseline Week 
3/TC 
Week 
6 
Week 
9/TC 
Month 
3 
Month 
6 
Month 
9/TC 
Month 
12 
 
Visit 1 
Visit 2 
Visit 3 
/TC 
Visit 4 
Visit 5 
/TC 
Visit 6 
Visit 7  
Visit 8 
/TC 
Visit 9 
Informed Consent 
X 
 
 
 
 
 
 
 
 
Documentation of 
FXTAS 
X 
 
 
 
 
 
 
 
 
Medical/Treatment 
Hx 
X 
 
 
 
 
 
 
 
 
Clinical Assessment 
 
X 
 
X 
 
X 
X 
 
X 
Neurological Exam 
 
X 
 
X 
 
X 
X 
 
X 


Adherence 
Assessments 
 
 
X 
X 
X 
X 
X 
X 
X 
Questionnaires 
 
X 
 
 
 
X 
X 
 
X 
FXTAS-RS and 
other rating scales 
 
X 
 
 
 
X 
X 
 
X 
Beck Anxiety/ 
CESDS-R scales 
 
X 
 
 
 
X 
X 
 
X 
Mini Mental State 
Exam (MMSE)_ 
X 
 
 
 
 
 
 
 
 
Neuropsychological 
battery of tests 
 
X 
 
 
 
X 
X 
 
X 
Computed 
Posturography/iTUG 
 
X 
 
 
 
X 
X 
 
X 
EKG 
 
X 
 
 
 
 
 
 
 
Lab tests 
X 
 
 
 
 
X 
X 
 
X 
Safety and 
tolerability phone 
call 
 
 
 
  
X 
 
 
X 
 
 
Pre-Intervention Evaluations 
These evaluations occur prior to the subject receiving any study interventions.  
• Screening 
At the screening visit, the subject will have diagnosis confirmed and medical history 
reviewed.  Inclusion and exclusion criteria will be completed. 
• Pre-Entry 
Screening and pre-entry may occur concurrently.  Consent will be obtained.  EKG and 
blood tests will be completed at the visit.  
 
On-Study Evaluations 
Blood chemistries, liver function tests, and hematology (Comprehensive Metabolic Panel 
[CMP] and CBC with differential) will be performed at Month 3, Month 6 and Month 12.  
FXTAS Rating Scale, neuropsychological tests, Computed Dynamic Posturography, 
instrumented Timed up and go test, and rating scales for movement disorders will be 
performed four times during the study.  The allowable time window is Schedule of 
Evaluations ±7 days.  
 
• Baseline 
The baseline (entry) visit will occur at least two weeks after the screening visit to allow 
for adequate study drug supply.  Study drugs will be dispensed at the entry visit.   
 
• Intervention Discontinuation Evaluations 
Evaluations done at the time of discontinuation include blood chemistry, hematology, 
FXTAS-RS, neuropsychological tests, Computed Dynamic Posturography, instrumented 
Timed up and go test, and the rating scales.  In addition, an adherence assessment will 
also be done.   
 
• Post-Intervention Evaluations 


Neurological examinations will be performed according to the standard of care by the 
treating neurologist/investigator.  
 
• Final Evaluations 
The final visit will consist of blood chemistry and hematology, neurological examination, 
FXTAS Rating Scale, neuropsychological tests, Computed Dynamic Posturography, 
instrumented Timed up and go test, rating scales, and adherence assessment.  
 
Special Instruction and Definitions of Evaluations 
 
The source document will include all of the following listed below.  
• Informed Consent:  The patient will have an opportunity to review the consent form 
and ask any questions prior to signing the form.  If the patient has dementia, they will 
be excluded from the study.  Documentation of the consent will be given to the 
subject, and copies will be maintained in the study chart and the hospital record.   
• Documentation of FXTAS: Diagnosis of FXTAS will need to be documented prior to 
entry in the patient’s chart.   
• Medical History: The subject’s history regarding FXTAS will be obtained or a record 
of this history secured for the study chart.  A complete social history, family history, 
and review of systems will also be performed.   
• Treatment History: Allergies will be reviewed.  Prior and current medications and 
other treatments will be reviewed and documented.  
• Clinical Assessments: Clinical assessment procedure will be reviewed at the baseline 
entry visit and neurological examination performed.  Clinical assessments to review 
safety, tolerability, and effectiveness will be conducted at each face-to-face visit or 
over the phone.  Neurological examination will occur at the face-to-face visits only.  
Change in neurological signs or symptoms, adverse events, or tolerability issues 
should be recorded on the CRFs. 
• Laboratory Evaluations: Blood chemistry and hematology will be performed and the 
resulting laboratory result form placed in the study record.  
• Questionnaires and Rating Scales: Scoring for each item on the FXTAS Rating Scale 
will be recorded in the scoring grid.  Scoring for the neuropsychological tests, CDP, 
iTUG, ABC, BAI, CESDS-R, and MoCA will be recorded in the CRF. 
• Adherence Assessments: Pill counts and questionnaires will be filled out at every 
phone or in person visit. 
 
Off-Intervention Requirements 
Recording of adverse events for subjects after the study will occur in the setting of 
regular care with the treating neurologist. 
 
FXTAS Rating Scale 
The FXTAS-RS was designed to measure the severity of motor signs of FXTAS, tremor, 
ataxia, and parkinsonism.  The scale was developed from a combination of three separate 
measures: the Clinical Rating Scale for Tremor (CRST), the International Cooperative 
Ataxia Rating Scale (ICARS), and the Unified Parkinson’s Disease Rating Scale 
(UPDRS).  The resultant scale has 44 items and a total score of 226.  The tremor sub-


domain (score range 0-53) assesses action and postural tremor, drawing, and handwriting.  
The ataxia sub-domain (0-73) assesses posture and gait, limb ataxia, dysarthria, and 
oculomotor disturbances.  The parkinsonism sub-domain (0-100) assesses bradykinesia, 
gait and balance, rest tremor, and rigidity (Tassone, 2010).  The FXTAS-RS is relatively 
safe and simple to administer.  It uses a quantitative scale format that has strong internal 
consistency and good inter- and intrarater reliability with different patient populations, 
including geriatric patients.  It has specifically been clinically validated for evaluating 
motor signs in FXTAS patients.   
For this study, improvement will be defined as a 20% improvement on the FXTAS-RS.   
 
MANAGEMENT OF ADVERSE EXPERIENCES 
There are no common adverse events with citicoline in adult studies.  Adverse events will 
be documented on the adverse event form and sent to the independent medical monitor.   
Due to its pharmacological effects on the dopaminergic system, citicoline may enhance 
the effects of L-Dopa.  Therefore, any subjects taking L-Dopa during the study will be 
monitored very closely for adverse events (EFSA, 2013).   
 
CRITERIA FOR INTERVENTION DISCONTINUATION 
Criteria and rules for stopping subject treatment include: new toxicological findings or 
serious adverse events, the patient withdraws consent without need for justification, the 
patient is no longer able to participate for medical reasons (such as surgery), if eligibility 
criteria are being violated, the subject develops significant neuropsychiatric symptoms 
such as suicidal ideation or psychosis, or if the subject fails to comply with the protocol.  
Subjects who stop treatment will still be asked to complete a final visit with rating scales 
and blood work. 
 
STATISTICAL CONSIDERATIONS 
 
General Design Issues 
The primary and secondary outcomes will be analyzed using SPSS.  The independent 
medical monitor will review adverse event data and the final analysis.  There will be no 
interim analysis performed.  There will be no stratification.   
 
Outcome and Data Analysis 
• Primary outcome (Aim 1):  The primary hypothesis will be tested using a paired t-test 
using means of the total FXTAS Rating Scale score before and after treatment.  
Linear regression will be used to determine if there is an association among outcome, 
gender, age, race, or ethnicity.  This outcome will be determined by the rating of 
patients from a blinded movement disorders neurologist.   
• Secondary outcomes (Aim 2):  Secondary hypotheses will be tested using paired t-
tests on the neuropsychological tests, CDP, iTUG, and the ABC scale.   
• Side effects (Aim 3):  Adverse events will be recorded and classified as to seriousness 
of the side effect and likelihood the side effect is related to the study drug. For side 
effect analysis, frequency analysis will be done.   
Sample Size and Accrual:  Sample size was estimated using published means and 
standard deviations of the FXTAS-RS in FXTAS subjects.  To allow for attrition, 10 


subjects will be recruited.  Intent to treat analysis will be performed.  The number of 
subjects lost to follow-up is likely to be low due to the relative lack of efficacy of 
other forms of treatment for this particular symptom of FXTAS.  For the FXTAS-RS 
outcome, a sample size of 58 patients is needed for a 20% effect size, using a mean 
score of 36.6 and a standard deviation of 11 with a mean change of -7.3, based on a 
power of 80% and α=0.5.  However, the first phase of testing is a pilot study looking 
at study methods and safety.  We will not have adequate sample size to determine 
efficacy, but will be able to use the pilot data to plan the larger phase III study.   
 
Data Monitoring 
An independent medical monitor will be identified to monitor this study.  An interim 
safety analysis will not be performed.  Guidelines for stopping the study would include 
new toxicological findings of citicoline or serious adverse events reported from the 
subjects on active medication.  The independent medical monitor will meet with the PI as 
needed during the protocol.   
 
DATA COLLECTION, SITE MONITORING, AND ADVERSE EXPERIENCE 
REPORTING 
 
Records to Be Kept 
All study forms will be kept at Rush University.  The records will be stored in a locked 
office of the site investigator.  At the main site, data on the CRF will be entered into a 
password protected database.  Access to the database will be restricted to the host site 
CRA, PI, and biostatistician. 
 
Quality Assurance 
The PI will meet with the study coordinator once monthly to review records, consent 
forms, protocol compliance, and data quality.  All of the investigators will meet once 
every four months to review issues related to quality.   
 
Adverse Experience Reporting 
Adverse events will be recorded on the adverse event CRF and reported within three 
days.  Serious adverse events will be reported within 24 hours.  Detailed definitions of 
adverse experiences, a table for grading their severity, and details of how clinical sites are 
to report them appear in the Manual of Operations.   
 
HUMAN SUBJECTS 
 
Institutional Review Board (IRB) Review and Informed Consent 
This protocol and the informed consent documentation and any subsequent modifications 
will be reviewed and approved by the IRB responsible for oversight of the study.  A 
signed consent form will be obtained from the subject.  Subjects who cannot consent for 
themselves cannot be included in the study.  The consent form will describe the purpose 
of the study, the procedures to be followed, and the risks and benefits of participation.  A 
copy of the consent form will be given to the subject, or legal guardian and this fact will 
be documented in the subject’s record. 


 
Subject Confidentiality 
All laboratory specimens, evaluation forms, reports, video recordings, and other records 
that leave the site will be identified only by the Study Identification Number (SID) to 
maintain subject confidentiality.  All records will be kept in a locked file cabinet.  All 
computer entry and networking programs will be done using the SIDs only.  Clinical 
information will not be released without written permission of the subject, except as 
necessary for monitoring by IRB, the FDA, the NINDS, the OHRP, the sponsor, or the 
sponsor’s designee. 
 
Study Modification/Discontinuation 
The study may be modified or discontinued at any time by the IRB, the NINDS, the 
sponsor, the OHRP, the FDA, or other government agencies as part of their duties to 
ensure that research subjects are protected.   
 
PUBLICATION OF RESEARCH FINDINGS 
Publication of the results of this trial will be governed by the policies and procedures 
developed by the Principal Investigator.   
 
FUTURE PLANS 
The proposed study constitutes a phase II clinical trial.  Upon completion of the study our 
plan is to conduct a phase III clinical trial of citicoline. 
REFERENCES CITED 
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Zas R, Alcaraz M, Secades JJ, Lozano R, Cacabelos R.  Double-blind placebo-
controlled study with citicoline in APOE genotyped Alzheimer’s disease patients. 
Effects on cognitive performance, brain bioelectrical activity and cerebral perfusion. 
Methods and Findings in Experimental and Clinical Pharmacology. 1999; 21(9): 633-
644.  
2. Qurashi A, Liu H, Ray L, Nelson DL, Duan R, Jin P. Chemical screen reveals small 
molecules suppressing fragile X premutation rCGG repeat-mediated 
neurodegeneration in Drosophila. Human Molecular Genetics. 2012; Vol 21, No. 9: 
2068-2075.