Measurement of Frataxin mRNA in Biofluids

Overview of the Study Participants will complete the study during 2 visits (visit 1 and 2). Visit 1 can be combined with a routine clinic visit for care or research but also may be done remotely via Zoom. During visit 1, the investigators will fully explain the study and obtain the participant's informed consent. For remote visits, a copy of the consent will be emailed to the participant before the visit and the study team will schedule a time to discuss the consent. The informed consent will be reviewed in detail with the participant, and they will have an opportunity to ask any questions before signing the document and agreeing to the study. In either case, once the participant agrees to the study after being fully informed, they will sign the consent document and a copy of it will be provided to them after the investigator signs it.

Once informed consent has been obtained, the participant will either schedule visit 1 or begin visit 1 that day. Visit 1 will last no more than 2 hours and will involve the collection of clinical data and the collection of a blood sample. The participant will be asked to obtain lab work before visit 2, these labs will be to test the participant's blood for its ability to clot well. This lab work will be reviewed before visit 2. Visit 2 will take no more than 4 hours and will involve the collection of spinal fluid. The participant will need to be accompanied by a driver at visit 2.

Description of Study Procedures

Blood Work prior to scheduled visit (~30 minutes)

• will need to go to one of the University of Florida Health's (UF Health's) local labs in Gainesville, Florida (FL) to have blood work done before the scheduled visit 2. This blood work will ensure that the participant meet the inclusion criteria before the spinal tap.

Overall health and safety assessment (~30 minutes)

• The participant's birthdate, gender, contact information, health history, current medications, and allergies will be obtained. The information will be stored in the participant's study file.
• If the participant is a woman of childbearing potential, a urine sample will be tested to see if they are pregnant. If the test is positive, the participant will not be able to continue in the study.
• The participant's FRDA DNA test from their medical record will be assessed and a copy placed in the research folder. No additional genetic testing will be performed.
• Measurements such as the participant's height, weight, blood pressure, pulse, respiratory rate, and temperature will be obtained.
• A general physical examination will be done by the study physician

Neurological examination, modified Friedreich Ataxia Rating Scale (mFARS), and blood sample (~30 minutes)

• The study physician will perform a neurological examination and use this to rate the participant's ataxia severity in the mFARS scale.
• This will include examining the participant's eye movements, speech, strength of their muscles, sensation, coordination in their arms and legs and ability to stand and walk among other things.
• The participant will be asked questions regarding their activities of daily living for a questionnaire called FRDA activities of daily living scale (FARS ADL).
• A blood sample of approximately 5-10 milliliters (or 1-2 teaspoonfuls) will be obtained.

Spinal Tap (~3 hours)

• About 15 milliliters or 1 tablespoon of cerebrospinal fluid (CSF) will be collected though a test called a spinal tap.
• The spinal tap will be performed in the interventional radiology suite at the Neuromuscular hospital via x-ray fluoroscopy.
• This procedure uses X-ray (fluoroscopy) to visualize their low back spine so that the spinal tap needle can be placed in the spinal sac in the participant's low back under visual guidance. This can minimize discomfort and can help increase the success of the procedure in one attempt.
• The participant will be given local anesthesia to numb the area before collection.
• The participant will be asked to relax while laying down following the procedure for 1 to 2 hours before leaving.

Inclusion criteria

• Patients with symptomatic Friedreich ataxia (men and women) related to documented biallelic GAA expansion in the FXN gene
• Age over 18 years
• No contraindication to spinal tap including any coagulopathy or local infections
• Competent to provide informed consent

Exclusion criteria

• Unable or unwilling to provide informed consent
• Any uncontrolled medical illness that may increase the risk of spinal tap such as ongoing infection as determined by the investigators
• FRDA related to an expansion in one allele and a conventional mutation on the other
• Positive pregnancy screening