Natural History Study of and Genetic Modifiers in Spinocerebellar Ataxias

• The disease's progression over time using clinical rating scales and timed performance measures. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
• Relation between the genetic modifiers and the age at onset of disease and disease progression rates. [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Spinocerebellar ataxias (SCA) are genetic neurological diseases that cause imbalance, poor coordination, and speech difficulties. There are different kinds of SCA and this study will focus on types 1, 2,3, and 6 (SCA 1, SCA 2, SCA 3 , also known as Machado-Joseph disease and SCA 6). The diseases are rare, slowly progressive, cause increasingly severe neurological difficulties and are variable across and within genotypes. The purpose of this research study is to bring together a group of experts in the field of SCA for the purpose of learning more about the disease.

The research questions are:

1. How does your disease progress over time?
2. What are the best ways to measure the progression?
3. Do some genes, other than the gene that is abnormal in your disease, have any effect on the way the disease behaves?

This is a nationwide study and we expect that 800 patients will participate all over the USA. The participants will be in the study for 2 years and have a total of 4 study related visits done every 6 months.

If you decide to participate in this study, we will collect 1 tablespoon (15 milliliters) of blood during the first/screening visit in order to extract your DNA. The sample will be sent to the research laboratory of Dr Stefan Pulst at the University of Utah for the study of genetic factors that modify the course of your disease.

As part of this study, we would like to put some of your blood in a tissue repository. Submission of your sample to the repository may give scientists valuable research material that can help them to develop new diagnostic tests, new treatments, and new ways to prevent diseases. Scientists will not use your sample, or material isolated from it, for commercial products or services. Your blood will be kept by Dr. Stefan Pulst.

Your sample will not have your name or other personal information linked to it. Your sample may be shared with researchers at the University of Utah and at other institutions. The only information we will keep with the sample is your age, what disease you have, the age at onset of your disease and the duration of the disease. The principal investigator at your site will be the only person who can link the sample to you. You can have your sample removed from the bank later by written request to your PI.

You do not have to participate in the genetic modifier study or the tissue repository to be in the remaining part of this study.

We will also ask twenty study participants who have the ability to walk to wear a small electronic monitor in the form of a light, non-painful ankle bracelet that will record information about your walking at home. The monitor is attached by Velcro and can be worn 24 hours a day, even in the shower. If you are one of the twenty people who will wear this device, known as a Step Activity Monitor (SAM), you will have the bracelet placed on your ankle during each visit. You will wear it continuously for the next eight days following the visit. You will be provided a self-addressed, pre-paid envelope in which to mail the monitor back so that we can collect that information.

You will also be asked to complete several assessments that include questionnaires, motor function test, a neurological exam and a physical exam.

The Clinical Research Consortium for Spinocerebellar Ataxias (CRC-SCA) is seeking subjects to participate in a clinical research study of patients with SCA 1, 2 3 and 6.

Potential participants should have symptoms of ataxia with a diagnosis of SCA 1,2,3 or 6 established by DNA tests either on the patient himself or herself or another affected family member and be between 18 and 80 years of age. In addition, patients who have ataxia with a dominant inheritance pattern but who do not yet know what type of SCA they have can also be screened for this project.

• Spinocerebellar Ataxia Type 1
• Spinocerebellar Ataxia Type 2
• Spinocerebellar Ataxia Type 3
• Spinocerebellar Ataxia Type 6

• Spinocerebellar Ataxia 1
• Spinocerebellar Ataxia 2
• Spinocerebellar Ataxia 3
• Spinocerebellar Ataxia 6

Inclusion Criteria:

• Presence of symptomatic ataxic disease
• Definite molecular diagnosis of SCA 1, 2,3,or 6 either in the subject or another affected family member
• Willingness to participate in the study and ability to give informed consent.
• Age 6 years and above

Exclusion Criteria:

• Known recessive, X-linked and mitochondrial ataxias
• Exclusion of SCA 1, 2, 3 and 6 by previous DNA testing,
• A lack of willingness to participate in the study