Transmissible Spongiform Encephalopathies

What are transmissible spongiform encephalopathies?

Transmissible spongiform encephalopathies (TSEs), also known as prion diseases, are a group of rare, degenerative brain disorders. Spongiform refers to the tiny holes that give the brain a "spongy" appearance in people with prion diseases. These holes can be seen when brain tissue is viewed under a microscope. 

TSEs cause problems with muscle coordination, thinking, and other symptoms. They tend to progress rapidly and usually cause death within a few months to a few years. 

Research suggests that an abnormal version of a protein called a prion (short for proteinaceous infectious particle) causes TSEs. Proteins are long chains of amino acids that fold together into a unique shape or conformation to help a cell function in a particular way. Prion proteins occur in both a normal form, which is harmless and found in the body's cells, and in an infectious form, which causes disease. The normal and harmless prion protein is found throughout the body but mostly in the nervous system. Its overall role is not fully understood. 

When a prion protein abnormally folds, this abnormal folding “transmits” to normal prion proteins in surrounding nerve cells (neurons). This causes the normal ones to change their shape and similarly become “infectious” to other neighbors. Once abnormal prion proteins form, they clump together and damage or destroy nerve cells. This nerve cell loss creates the sponge-like holes in the brain and leads to TSE symptoms.   

Symptoms of TSEs

Symptoms of TSEs vary, but they commonly include:

• Cognitive decline
• Personality changes (such as irritability)
• Psychiatric problems (such as depression)
• Lack of coordination
• Unsteady walking

People with TSEs also may have involuntary jerking movements (called myoclonus), unusual sensations, insomnia, seizures, or vision problems. In the later stages of the disease, people will typically have severe mental impairment and lose the ability to move or speak.

Types of TSEs

Creutzfeldt-Jakob disease (CJD) and variant CJD is the most well-known of TSEs in humans. Other types of human TSEs include:

Gerstmann-Straussler-Scheinker disease (GSS) 

GSS is an extremely rare, neurodegenerative brain disorder that is almost always inherited and found in only a few families around the world. GSS usually begins between ages 35 and 55. 

In the early stages, people with GSS may have different levels of muscle coordination challenges—including clumsiness, unsteadiness, and difficulty walking. As the disease progresses, most people develop dementia. Other symptoms may include trouble speaking clearly, rigid muscle tone (spasticity), vision and eye problems, and deafness. In some families, people also have tremor. 

GSS is a slowly progressive condition that usually lasts from 2to 10 years. It ultimately causes severe disability and finally death.  

Kuru 

Kuru is a very rare and fatal brain disorder that was an epidemic in the 1950s and 1960s among the Fore people in the highlands of New Guinea. Kuru is the Fore word for shiver. Kuru came from the practice of ritualistic cannibalism among the Fore, where relatives prepared and ate the tissues (including brain) of deceased family members. Brain tissue from people with Kuru was highly infectious, and the disease was transmitted either through eating or by contact with open sores or wounds. 

Kuru’s symptoms included unsteady gait, tremors, and slurred speech. Some people experienced changes in mood. Eventually, people with Kuru couldn’t stand or eat, and they died in a comatose state between 6 and 12 months after the first symptoms appeared. The government of New Guinea discouraged cannibalism, contributing to a continuing decline in the disease—which has now mostly disappeared.

Fatal Familial Insomnia (FFI)

FFI is a prion disease that causes dramatic and progressive insomnia and disruption of normal sleep-wake patterns. Problems with the body’s automatic functions (like regulating body temperature, heart rate, sweating), weight loss, voice changes, and other CJD-like symptoms can also develop. 

Mutations in the gene that codes for prion protein (PRNP) typically cause FFI. But some cases of fatal insomnia can develop without a gene mutation.

Variably protease-sensitive prionopathy (VPSPr) 

VPSPr is a very rare, sporadic (not inherited) TSE. Common symptoms include trouble speaking clearly, psychiatric symptoms, and cognitive impairment. Tremors, slow movement, rigid muscle tone, and loss of muscle coordination can develop. 

Researchers haven’t identified a gene mutation that causes VPSPr. It’s different from other TSEs because proteases (enzymes that break down protein) can more easily break down the prions in VPSPr than in other TSEs. Normal prion proteins are protease sensitive, but most abnormal prion proteins aren’t easily broken down by proteases, resulting in cell death. Some variants are more sensitive to proteases than others, so this is called variably protease-sensitive prionopathy. Research is ongoing to determine other similarities and differences between CJD and VPSPr infectious prions.

TSEs can also develop in certain animals, and these disorders could potentially transmit to humans in some cases. Animal TSEs include:

• Bovine spongiform encephalopathy (BSE or “mad cow” disease)
• Mink encephalopathy
• Feline encephalopathy
• Scrapie (which affects sheep and goats)
• Chronic wasting disease (CWD) (which affects elk, reindeer, moose, and deer)   

In a few rare cases, TSEs have happened in other mammals, such as zoo animals. Contaminated feed probably caused these cases. 

Who is more likely to get transmissible spongiform encephalopathies?  

There are three ways that people may develop TSEs. These include:

• Sporadic: Sporadic TSEs may develop because some of a person's normal prions spontaneously change into the infectious form of the protein. The infectious ones then alter the prions in other cells in a chain reaction.
• Hereditary: Inherited cases result from a change, or mutation, in the prion protein gene that causes the prions to form in an abnormal way. Parents may transmit this genetic change to their children.
• Transmission from infected people: Transmission of TSEs from infected people is relatively rare. People can’t transmit TSEs through the air or through touching or most other forms of casual contact. But contact with infected tissue, body fluids, or contaminated medical instruments may transmit TSEs. Normal sterilization and cleaning procedures, such as boiling or irradiating materials, doesn’t prevent transmission of TSEs. 

How are transmissible spongiform encephalopathies diagnosed and treated? 

Diagnosing TSEs

To diagnose TSEs, a healthcare provider will do a physical exam and ask about the person’s medical history. Depending on the findings, a doctor can use a few other tests to help diagnose TSEs: 

• A neurological exam to check for problems with the nervous system
• Blood tests to rule out other conditions with similar symptoms
• Electroencephalography (EEG), which looks at brain waves by placing electrodes on the scalp
• Cerebrospinal fluid (CSF) tests through a lumbar puncture (spinal tap) to detect the abnormal prion protein in the fluid that surrounds the brain and spinal cord 
• MRI (magnetic resonance imaging) scans of the brain
• Genetic tests to look for known hereditary causes of TSEs 

Learn more about neurological diagnostic tests and procedures.

While these tests can help doctors make a likely diagnosis of TSEs during life, the way to conclusively confirm a diagnosis of a TSE—such as CJD—is by brain biopsy or an autopsy. In a brain biopsy, a neurosurgeon removes a small piece of tissue from the living person's brain so it can be examined by a neuropathologist. This procedure may be dangerous for the person and is generally discouraged unless it’s needed to rule out a treatable disorder. In an autopsy, a doctor will examine the whole brain after death.

Treating TSEs 

Currently there’s no cure for any type of TSEs. Treatment is aimed at easing symptoms and making the person as comfortable as possible.  

What are the latest updates on transmissible spongiform encephalopathies?  

NINDS, part of the National Institutes of Health (NIH), is the nation’s leading federal funder of research on neurological disorders. As part of its mission, NINDS conducts and funds research on TSEs. Other NIH institutes, including the National Institute of Allergy and Infectious Diseases (NIAID), also conduct research on TSEs. 

New treatment strategies for TSEs focus on using drugs, gene therapy approaches, or a combination of both that reduce the expression of the natural prion protein to eliminate the potential for misfolding and clumping. Researchers are seeking to discover and understand other potential effects of removing healthy prion proteins. 

NIH-funded researchers have developed a molecular tool, “CHARM,” (short for Coupled Histone tail for Autoinhibition Release of Methyltransferase), that can silence prion protein throughout the brain using epigenetic editing. This may be a promising path for developing a treatment for prion diseases and other neurodegenerative conditions that involve toxic protein build-up in the brain. Unlike gene editing approaches, which change the sequence of genes, epigenetic editing can turn gene expression off with the addition of a chemical tag that prevents genes from being translated into proteins. Such a strategy may be able to deliver modifying tools to silence specific toxic or disease-causing genes—including the one encoding the prion protein—without the risks associated with altering DNA sequences. When CHARM was delivered to the mouse brain, prion protein levels dropped by more than 80%. Earlier studies have shown that reducing prion protein by as little as 20% can improve symptoms. 

An evolving topic of recent research interest has been whether the misfolded proteins characteristic of Alzheimer’s disease and Alzheimer’s disease-related dementias (AD/ADRD) replicate in the brain through “prion-like” mechanisms. These various dementia-causing conditions are associated with their own disease-specific protein buildups. But emerging evidence suggests that these buildups can produce a chain reaction of protein misfolding and replication in the brain—which is very similar to what happens with the cellular prion protein in CJD and other TSEs. 

The cellular prion protein itself has also recently been shown to be a cell-surface receptor for amyloid-beta (a protein) that may make them less harmful to the brain. NIH-funded researchers are currently studying the cellular and molecular mechanisms by which prion-like conversion events happen and are reproduced in AD/ADRD. These studies draw heavily on existing knowledge about how traditional TSEs arise. 

More information about TSEs research may be found using NIH RePORTER, a searchable database of current and past research projects supported by NIH and other federal agencies. RePORTER also includes links to publications and resources from these projects.

For research articles and summaries on TSEs, search PubMed, which contains citations from medical journals and other sites. 

How can I or my loved one help improve care for people with transmissible spongiform encephalopathies?

Clinical trials increase our understanding of TSEs with the goal of improving how doctors treat them. Consider participating in a clinical trial so clinicians and scientists can learn more about TSEs. Clinical research with human study participants helps researchers learn more about a disorder and perhaps find better ways to safely detect, treat, or prevent disease.

All types of volunteers are needed—those who are healthy or may have an illness or disease—of all different ages, sexes, races, and ethnicities to ensure that study results apply to as many people as possible, and that treatments will be safe and effective for everyone who will use them.

For information about participating in clinical research visit the NINDS Clinical Trials site and NIH Clinical Research Trials and You. Learn about clinical trials currently looking for people with TSEs at Clinicaltrials.gov, a searchable database of current and past clinical studies and research results.

Learn about related topics

• Creutzfeldt-Jakob Disease