What is Creutzfeldt-Jakob Disease?
Creutzfeldt-Jakob Disease (CJD) is a rare degenerative brain disorder caused by defective proteins that damage brain tissue. CJD causes dementia that may appear similar to that caused by Alzheimer’s disease. However, CJD progresses more rapidly than Alzheimer’s and is always fatal.
Symptoms of CJD
Common early symptoms of CJD include:
- Changes in personality
- Memory impairment
- Problems with coordination
- Vision impairment
- Speech problems
- Sleep disruptions
- Involuntary, jerking muscle movements
What Causes Creutzfeldt-Jakob Disease?
CJD is caused by a protein called a prion. Prions exist in normal cells and are usually harmless. However, in CJD and other diseases called transmissible spongiform encephalopathies (TSEs), abnormally formed prions cause damage to cells in the brain and the central nervous system. These abnormal prions also make other prions develop abnormally, causing the disease to spread and produce progressively worsening symptoms.
CJD is divided into subtypes that have different causes:
- Sporadic CJD seems to occur randomly for no apparent reason. This is the most common type of CJD and accounts for about 85 percent of all cases.
- Hereditary CJD is caused by an abnormal change (mutation) in a gene and runs in families. About 10-15 percent of CJD cases are inherited.
- Acquired CJD is passed from one affected person to another. Transmission is usually through contact with infected brain tissue or cerebrospinal fluid and may occur during medical procedures. This type of CJD is rare.
- Variant CJD (vCJD) has been associated with meat consumption from cattle infected with a TSE. This type of CJD is extremely rare.
Is Creutzfeldt-Jakob Disease Hereditary?
Hereditary CJD is caused by abnormal changes in the gene that carries instructions for making the prion protein. Researchers have identified several different mutations associated with the disease, and the specific mutation involved appears to affect the symptoms and frequency of the disorder.
Familial cases of CJD are inherited in an autosomal dominant pattern, meaning that children may develop the disorder if they inherit even one copy of the mutated gene from either of their parents. If a parent carries the disorder-causing mutation, they will have a 50 percent chance of having an affected child with each pregnancy. The parent may also develop CJD themselves, but not everyone with a mutated prion gene will develop the disease.
How Is Creutzfeldt-Jakob Disease Detected?
The earliest symptoms of CJD are similar to those of Alzheimer’s disease and other forms of dementia. However, CJD typically progresses much more quickly than other types of dementia, and death usually occurs in a matter of months.
Early symptoms of CJD can include:
- Personality changes
- Memory loss
- Coordination problems
- Vision impairment
Psychiatric symptoms are commonly the earliest signs of vCJD, and this form of the disease often progresses more slowly than other types.
How Is Creutzfeldt-Jakob Disease Diagnosed?
No single test can reliably identify CJD, but some tests and exams can help diagnose the disease and rule out other potential causes of the symptoms. Possible diagnostic steps include:
- Electroencephalography (EEG) to measure brain activity. Some cases of CJD show a distinctive pattern of electrical activity in the brain.
- Magnetic resonance imaging (MRI) may detect the pattern of brain degeneration characteristic of CJD.
- Tests of the cerebrospinal fluid (CSF) may detect proteins associated with defective prions or the abnormal prions themselves.
While these tests may suggest the presence of CJD, only a postmortem autopsy of brain tissue can definitively diagnose the disease.
PLEASE CONSULT A PHYSICIAN FOR MORE INFORMATION.
How Is Creutzfeldt-Jakob Disease Treated?
CJD has no cure, and no treatment will halt or reverse the progression of symptoms. Treatment options such as pain medications focus on improving the patient’s quality of life as much as possible.
How Does Creutzfeldt-Jakob Disease Progress?
CJD is progressive, and symptoms worsen quickly. Most cases are fatal within less than a year after the initial onset of symptoms. People with variant CJD (vCJD) may survive somewhat longer.
Long-term and potentially fatal complications of CJD can include:
- Pneumonia or other respiratory infections
- Respiratory failure
- Heart failure
How Is Creutzfeldt-Jakob Disease Prevented?
There is no known way to prevent sporadic CJD. A genetic counselor can advise people with a family history of hereditary CJD about their risk if they plan to have children.
Practices to help prevent acquired CJD include:
- Medical procedure rules to protect medical professionals from exposure to infected tissue
- Restrictions on blood donation from people at risk of exposure to CJD
- Regulations on commercial meat producers to prevent infected livestock from entering the food supply
- Avoidance of game meat in areas where animal TSEs (such as chronic wasting disease in deer) is common
Creutzfeldt-Jakob Disease Caregiver Tips
- Take care of yourself. Caregivers for people with a progressive disease like CJD are susceptible to mental and physical health problems if they don’t take care of themselves. Don’t feel guilty for needing occasional time away from the demands of caregiving, and don’t hesitate to ask for help from family and friends.
- Find sources of support. Organizations such as the Creutzfeldt-Jakob Disease Foundation can guide you to educational resources, support groups, and contact with other families affected by CJD.
Creutzfeldt-Jakob Disease Brain Science
Prion proteins are long chains of amino acids that occur in normal cells, especially in nerve cells in the brain. Scientists are not yet sure of the role prions play in healthy brain cells, but when prions become deformed, as they do in CJD and other TSEs, they clump together. These abnormal protein clumps seem to impair brain cell function and lead to cell damage and death.
Prion diseases are infectious and progressive because abnormal prions cling to normal prions and cause the normal prions to become deformed. In this manner, abnormal prions spread through infected tissue and cause progressive brain damage.
Creutzfeldt-Jakob Disease Research
Title: CJD (Creutzfeldt-Jakob Disease) Quinacrine Study
Principal Investigator: Michael Geschwind, MD, PhD
University of California, San Francisco
San Francisco, CA
Creutzfeldt-Jakob disease (CJD)is a rapidly progressive, invariably fatal, and untreatable neurodegenerative disease with a mean duration of about eight months. Beyond the debilitating cognitive and motor deficits that accompany CJD, the difficulty in treating behavioral and mood disturbances and the rapidity of its course compound its tragedy. Recent experiments show that, at physiological concentrations, the anti-malarial drug quinacrine permanently clears abnormal prion proteins from cell culture. The demonstrated efficacy of quinacrine in cell culture, its relative safety and well-known side-effects in the clinical setting, and the universal fatality of CJD justify quinacrine as an immediate candidate for the treatment of CJD.
The purpose of this clinical trial is to determine the efficacy of the medication quinacrine on survival in sporadic CJD (sCJD). This will be accomplished by bringing approximately 60 patients with probable or definite sCJD over approximately three years to UCSF for evaluation and initiation of a randomized, double-blinded, placebo-controlled (delayed treatment start) treatment study of quinacrine. Each patient will have a 50:50 chance of being placed on quinacrine or placebo upon study enrollment; however, all patients will be offered quinacrine after two months. Before study enrollment, patients will have a comprehensive clinical assessment to confirm the diagnosis of sCJD. Participants will come to UCSF for initial evaluation, potential study enrollment, and, if possible, return to UCSF for follow-up at two and twelve months. Patients will receive telephone follow-ups (every two weeks for the first two months and monthly thereafter) and local blood and testing to monitor for possible medication toxicity.
Title: The Role of the Coagulation Pathway at the Synapse in Prion Diseases
Stage: Not Yet Recruiting
Principal investigator: Oren Cohen, MD
Sheba Medical Center
The study hypothesis is that the harmful effect of prions on the brain may be mediated (at least partially) by the activation of serine proteases involved in the coagulation system. If this is true, then measurement of the activity of the coagulation system may be a marker of disease onset (in higher-risk individuals such as E200K* carriers) and for disease progression or activity in affected individuals. In addition, modulation of the coagulation system activity may be a potential tool for therapeutic intervention.
We plan to collect Cerebrospinal fluid (CSF) samples for thrombin activity assay to test whether there is a difference in thrombin activity in the CSF between CJD (Creutzfeldt-Jakob disease) and non-CJD patients. CSF samples will be obtained from two sources 1. Patients with familial or sporadic CJD and control patients with other neurodegenerative disorders (e.g., SDAT**, NPH) will be evaluated in Sheba Medical Center 2. From our collaborating group of Prof. Zerr in the German Prion Referral Center at the University of Gottingen, which has a collection of thousands of CSF samples from patients with familial and sporadic CJD as well as ideal controls with other degenerative brain diseases.
The study has two sections:
Prospective part in which we plan to recruit 25 patients with CJD and 25 patients with other types of dementia from Sheba Medical Center (SMC). Before inclusion in the study, a senior neurologist will interview the patient and will verify that they fully understand the objectives of the study, and they are mentally qualified to sign the informed consent form (severely demented patients who will not be able to adequately consider participation in the study will be excluded).
Cognitive performance will be evaluated using the Mini-mental Status Examination and Frontal Assessment Battery scales.
No clinical data other than the cognitive assessment and those needed for the clinical workup will be especially collected for this study.
CSF samples from CJD patients and patients with other types of dementia will be shipped to us from our collaborators in Germany and will be assayed for Thrombin activity. We plan to recruit 100-200 CJD patient CSF samples and an equal number of samples from age-matched controls to this part of the study.
Thrombin activity (for samples from both parts of the study) will be assayed as follows: CSF sample will be placed in a black 96 well dish (10 per well). A fluorometric assay will measure thrombin activity, quantifying the cleavage of the synthetic peptide substrate Boc-Asp(OBzl)-Pro-Arg-AMC*** (I-1560, Bachem, Switzerland, 13 molar final concentration). Measurements will be performed by the Infinite 2000 microplate reader (Tecan, infinite 200, Switzerland) with excitation and emission filters of 360±35 and 460±35 nm, respectively. CSF testing for thrombin activity will be conducted in Professor Chapman’s laboratory in Sheba. This laboratory is actively engaged in research on the role of thrombin and PAR-1 in diseases of the nervous system and is fully equipped to perform the biochemical and protein levels experiments.
The assay has the potential for commercialization as a diagnostic test for CJD. In addition, there is the potential to develop therapeutic agents targeting excessive thrombin activation.