Neurodegenerative disorders are among the most common to affect us as we age. They include, but are not limited to, Alzheimer’s disease, Parkinson’s disease, Amyotrophic Lateral Sclerosis (ALS, Lou Gehrig’s disease), and Multiple Sclerosis (MS). All of these disorders are genetic, in part. We have focused on a number of diseases with a strong genetic basis. By cloning genes causing strongly genetic forms of neurodegenerative disease, we hope to better help affected individulas and to gain insights into neurodegeneration more globally.

Autosomal Dominant Leukodystrophy (ADLD)

Leukodystrophy refers to a group of genetic disorders that are characterized by the imperfect development or maintenance of the white matter (myelin sheath covering nerve fibers in the brain). Adult-onset autosomal dominant leukodystrophy (ADLD), is a slowly progressive, neurological disorder characterized by symmetrical widespread myelin loss in the CNS. The ADLD phenotype is similar to that of chronic progressive multiple sclerosis (MS). It is characterized by development of autonomic dysfunction e.g. (low blood pressure, incontinence, and blurred vision). In contrast to MS patients, ADLD sufferers experience earlier autonomic dysfunction. CT scans/MRIs of ADLD patients illustrate the widespread symmetrical demyelination that occurs, as opposed to the asymmetrical demyelination exhibited in MS. In addition, large families segregating a highly penetrant autosomal dominant MS allele have not been described.

Our Research

Linkage analysis has already localized ADLD to chromosome 5q31 and we hope to isolate the ADLD gene through fine genetic mapping. ADLD represents a model for monogenic demyelination, and identification of the ADLD gene and its encoded protein could provide further insight into the molecular mechanisms of myelin assembly and maintenance. Therefore the study of this disorder could enhance our understanding of the pathogenesis of non-Mendelian demyelinating diseases such as MS and may provide novel therapeutic targets for development of new treatments.

Spinocerebellar Ataxia 4 & 7 (SCA4, SCA7)

The hereditary ataxias are a group of genetic disorders producing slowly progressive incoordination of gait and often associated with poor coordination of hands, speech, and eye movements. Ataxia may result from dysfunction of the cerebellum and its associated systems, lesions in the spinal cord, peripheral sensory loss, or any combination of these three conditions. In some families with SCA, there is an associated retinal or peripheral nerve degeneration that can lead to blindness or neuropathy which is the case in SCA7 and SCA4 respectively. SCA4 is distinct from other SCAs because the neuropathy is frequently the earliest sign of the disease and is always found in affected individuals. Patients with SCA4 may not be able to sense their position when they have their eyes closed resulting in unsteadiness. Reflexes are absent in many patients and there is decreased sensation to touch.

Our Research

All but two of the genes predisposing individuals to SCA that have been identified so far are caused by polyglutamine tract expansions. In individuals with expanded alleles, CAG repeat length correlates with disease progression and severity. These findings have led to the hypothesis that expanded polyQ tracts may be toxic to cells in the CNS. The disease-causing gene for SCA4 has been linked to chromosome 16q22.1 and we are working very hard to clone the gene.

Parkinson’s Disease

Parkinson’s disease (PD) is a slowly progressive, chronic neurological condition that affects a small area of the brain, the midbrain. Degeneration of cells in this region of the brain results in a reduction of the chemical dopamine. A decrease in dopamine produces signs of Parkinson’s disease that may include a resting tremor of one or both hands, slowness of body movement, rigidity of limbs, and gait or balance problems. Most people who develop Parkinson’s disease have “Idiopathic Parkinson’s Disease” meaning that the cause of the disease is unknown. Once considered non-genetic in etiology, within certain families there are multiple individuals with Parkinson’s disease. This suggests that the disease may be genetically inherited in those families.

Our Research

By studying families affected by Parkinson’s disease, we hope to localize and eventually clone the disease-causing gene for Parkinson’s disease. This approach will not only facilitate a greater understanding of this disease but hopefully provide greater insight into the genetic of neurodegeneration in general.

Amyotrophic Lateral Sclerosis (ALS)

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Multiple Sclerosis (MS)

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Participate in a Research Study

For our neurodegenerative studies, we are currently enrolling participants affected by ADLD and SCA 4.

As an initial screening process, you will be asked about your medical history. These questions are used to determine if you would be a good candidate for our studies. Dr. Ptacek will review your information and determine your eligibility for participation. Participants will then sign consent forms detailing the study objectives, UCSF health privacy policy, and procedures and donate either a blood or saliva sample for DNA extraction. We may also request clinical files or other medical records.

We would truly appreciate hearing from you if you feel you have any of these neurological disorders and are interested in participating in our studies.

Please refer to our Contact Page for more instructions.

We are currently not enrolling participants for the other neurodegenerative disorders. However, we may open enrollment in the future. If you would like to be contacted in the future for our circadian studies, please contact our clinical coordinators with your information. Please refer to the Contact Page for more information.

Other Neurodegeneration Resources

For more information, please visit the following sites: