Corticobasal Degeneration

What Causes Corticobasal Degeneration?

CBD is caused by the deterioration of the parts of the brain that control movement and thought processes, especially the cerebral cortex and the basal ganglia. The cerebral cortex is responsible for cognitive functions, and the basal ganglia help control voluntary movement.

Scientists don’t know what causes brain degeneration in CBD, but research has shown that people with CBD have an accumulation of proteins called tau in their brains. Accumulations of tau protein have also been associated with Alzheimer’s disease and other degenerative brain diseases.

Is Corticobasal Degeneration Hereditary?

In most cases, CBD does not seem to be inherited. Most people with CBD have no family history of the disorder. Researchers have found an association between some CBD cases and abnormal changes (mutations) in a gene that carries instructions for making tau protein. However, not everyone with the mutated gene has CBD, and not everyone with CBD has the mutated gene.

The link between these gene mutations and the disorder suggests a genetic component to CBD risk, even if it is not directly inherited. Scientists believe that an interplay of genetic predispositions and environmental factors likely cause CBD.

How Is Corticobasal Degeneration Detected?

Early diagnosis of CBD is challenging because its symptoms so closely resemble those of other neurological diseases, and misdiagnosis of CBD is common. For example, the movement-related symptoms of CBD are similar to those of Parkinson’s disease, but CBD symptoms often begin on only one side of the body before progressing to involve both sides.

How Is Corticobasal Degeneration Diagnosed?

No test or exam can definitively detect CBD. Doctors must be careful to rule out other similar disorders, such as progressive supranuclear palsy, Alzheimer’s disease, Pick’s disease, and Creutzfeldt-Jakob disease, before making a CBD diagnosis.

The diagnostic process may include:

• Physical exams and neurological exams to rule out other possible causes of the symptoms
• Magnetic resonance imaging (MRI) or computerized tomography (CT) scans to look for brain degeneration in the parts of the brain associated with CBD.

PLEASE CONSULT A PHYSICIAN FOR MORE INFORMATION.

How Is Corticobasal Degeneration Treated?

No treatment will stop the progression of CBD or reverse the effects of its symptoms. Instead, most treatments aim to reduce the impact of symptoms, improve quality of life, and prevent life-threatening complications. Possible treatment options include:

• Some drugs used to treat Parkinson’s, such as levodopa, may minimally and temporarily ease movement symptoms in some cases.
• Botulinum toxin or baclofen may help treat pain and rigid joints (contractures).
• Clonazepam may help relieve muscle twitching.

Other treatments and therapies include:

• Physical therapy
• Occupational therapy
• Speech therapy
• Mobility assistive devices

How Does Corticobasal Degeneration Progress?

CBD symptoms worsen slowly but steadily, and most people with the disorder will not survive beyond 6-8 years from the initial appearance of symptoms. Long-term and life-threatening complications can include:

• Loss of the ability to walk
• Loss of speech
• Difficulty swallowing
• Blood infections (sepsis)
• Bacterial infections
• Respiratory infections such as pneumonia
• Respiratory failure caused by blood clots in the lungs (pulmonary embolism)

How Is Corticobasal Degeneration Prevented?

There is no known way to prevent CBD.

Corticobasal Degeneration Caregiver Tips

• Educate yourself about the disease and its effects and the side effects of medications used to treat it. People with CBD are also at higher risk of developing depression and anxiety. Be on the lookout for the warning signs of these conditions.
• Join a support group for caregivers. Caregivers are at risk of developing physical and mental health issues, too. So take time for yourself, and get the help you need when you feel overwhelmed.

Corticobasal Degeneration Brain Science

Tau protein is normally present in brain cells, and it plays an essential role in the health and function of the cells. However, in tau-related degenerative diseases (tauopathies), the protein takes on an abnormal form and destroys protein filaments in the cells. Scientists believe that the destruction of these filaments causes the cells to die.

In CBD, tau accumulates in the cerebral cortex and the basal ganglia, causing damage to nerve cells in these parts of the brain. Over time, the affected cells die, leading to a gradual shrinkage of these vital brain structures. The cerebral cortex is the outer layer of brain cells that covers the largest part of the brain, the cerebral hemispheres. It is involved in many crucial functions, including memory, learning, voluntary movement, and processing of sensory input. The basal ganglia are structures deep within the brain that are involved in processes such as movement and learning. As these parts of the brain begin to deteriorate, the symptoms of CBD result.

Corticobasal Degeneration Research

Title: 4 Repeat Tauopathy Neuroimaging Initiative (4RTNI)

Stage: Recruiting

Principal investigator: Adam Boxer, MD, PhD

University of California, San Francisco

San Francisco, CA

The purpose of this study is to evaluate several different tests, including brain imaging, eye movement testing, body fluid samples, measurements of memory and other thinking abilities, and measures of functional independence in the hope that this information can be used to guide diagnosis and treatment of PSP and CBD in the future. Recent advances in our understanding of the biological causes of these diseases offer hope for new treatments. As such treatments are developed, sensitive and specific biological measurements (biomarkers) will be needed to provide precise and direct measures of the state of the brain, which will improve the statistical power of clinical trials. Brain imaging with Magnetic Resonance Imaging (MRI) has previously been used to measure disease-related changes in the brain. This study aims to identify the best methods of analysis (including eye movements, imaging, and behavioral measures) for tracking PSP and CBD over time. In addition, specific biomarkers in the blood and cerebrospinal fluid might also be useful for following these diseases over time. This study will examine the value of blood and CSF biomarkers relative to brain imaging and functional measures.

Title: Rho Kinase (ROCK) Inhibitor in Tauopathies – 1 (ROCKIT-1)

Stage: Recruiting

Principal investigator: Peter Ljubenkov, MD

UCSF Weill Institute for Neurosciences

San Francisco, CA

This is a Phase 2a Open-Label Preliminary Safety, Tolerability, and Biomarker Study of Oral Fasudil in Patients with the 4-Repeat Tauopathies of Progressive Supranuclear Palsy-Richardson Syndrome or Corticobasal Syndrome.

After consent, participants will undergo screening evaluations, which may occur over up to 6 weeks. Subjects who meet inclusion/exclusion criteria will be enrolled in the study and complete baseline evaluations. Dosing with the study drug will begin on Day 1 and continue for 48 weeks. Participants will return to the clinic at Week 1 (7 ± two days after the first study drug administration) and Weeks 12, 24, 36, and 48 for study evaluations and at Week 52 for post-treatment follow-up evaluations. Plasma biomarker collection will occur at baseline and Weeks 12, 24, 36, and 48. Cerebrospinal fluid (CSF) Biomarker collection will occur at screening, Week 24 and Week 48. Brain magnetic resonance imaging (MRI) will occur at screening and Weeks 24 and 48. Safety labs will be collected at each study visit as well as during Week 4.

Adverse events (AEs) will be assessed at all visits, and subjects will be contacted one day after the start of treatment (that is, one day after Visit 1) and monthly thereafter, including at each visit. The subject will also be contacted one day after Visit 6/last day of dosing with study drug for subjects who discontinue early.

Subjects/caregivers will be queried for study drug compliance one day after the start of treatment (that is, one day after Visit 1) and monthly thereafter.

Title: Human CNS Tau Kinetics in Tauopathies (TANGLES)

Stage: Recruiting

Principal investigator: Randall Bateman, MD

Washington University in Saint Louis Medical School

Saint Louis, MO

This study aims to characterize tau kinetics and tau aggregation in the human CNS and test the hypothesis that tau kinetics are altered (i.e., increased production, decreased clearance, and increased aggregation rate) in tauopathies.

Tauopathies are neurodegenerative diseases with tau pathology. These tauopathies are the most common pathology in neurodegenerative diseases, and they are reaching epidemic proportions. Therefore, the rates of tau kinetics are central to understanding normal and abnormal processing and production and clearance of tau kinetics in humans to help understand the causes of tauopathy and evaluate tau-targeted therapeutics.

This study will utilize the Stable Isotope Labeling Kinetics (SILK) method to elucidate tau kinetics in vivo in the human central nervous system (CNS) and its alteration in tauopathies. A total of ~34 participants from 3 different neurodegenerative diseases: Frontotemporal Dementia (FTD), Corticobasal Degeneration (CBD), and Progressive Supranuclear Palsy (PSP), will be invited to enroll in the study.

Participants will be labeled with stable isotopes via 16hr intravenous infusion and CSF samples collected during subsequent lumbar puncture visits over ~120 days. In addition, CSF will be analyzed over time for the quantitation of labeled tau.