Prions Research Paper

Prions: Proteinaceous Infectious Particles

A Prion is a controversial infectious agent made up of misfolded proteins, which, unlike all other known infectious agents, doesn’t contain any nucleic acids (KJ Ryan 624). Prion molecules are the cause of numerous fatal diseases which attack sensitive neural tissue and are, as to date, virtually untreatable mostly due to inadequate awareness and funding for research (Prusiner). A well-funded focus on Prion research could bring us closer to finding cures for the associated diseases as well as unlock doors to more information on neural infections in general.

Prions were discovered by Dr. Stanley Prusiner in 1982 after one of his patients died of Creutzfeldt-Jakob Disease. He was able to trace the cause

to a single protein, which he coined Prion, a mesh word meaning proteinaceous infectious particle (Prusiner). He went on to be awarded the Nobel Prize in medicine for his discovery, but even then, the concept of a rogue protein was largely seen as heretical by the scientific and medical communities and many refused to acknowledge its existence. Despite skepticism, in 1983 Leroy Hood agreed to a collaboration project in which Prusiner combined his procedure for isolating small quantities of proteins with Hood’s newly developed protein sequencer to begin cloning Prions, and creating a basis that allowed them to be studied on the molecular level.
Perhaps the biggest impact of the time was discovering just how many diseases that had dumbfounded medical professionals in the past were actually linked to the Prion Protein, most notably Bovine Spongiform Encephalopathy or “Mad Cow Disease,” Creutzfeldt-Jakob Disease, and Kuru, nicknamed the “Laughing Sickness” for its victims experiencing uncontrollable fits of laughter (Prusiner).
The neurodegenerative properties of Prions are due to their tendency to congregate near the Central Nervous System and clumping together into amyloids which causes inflammation and sponge like holes to occur in the tissue which can cause things such as dementia, convulsions and personality changes as well as a slew of other things (F.Morinet).
Prions can arise in a host through hereditary means or even spontaneous conversion, but the most common form of transmission is through ingestion. These fatal proteins are almost impossible to destroy and can lay dormant for fifty or more years. They are often found on and contracted from animal carcasses or dung, occasionally contaminating water supplies or being eaten by animals, either of which risks widespread transmission.
Kuru became a major problem during the 1950s for tribes in Papua New Guinea due to mass Prion spread via ritualistic cannibalism traditions in which members of the Fore tribe would consume their relatives after their passing away (O. Bannach, D. Riesner).
The most common form of Prion related disease in human is Creutzfeldt-Jakob Disease or CJD. Very little is known about CJD. It causes many neurological problems such as dementia, prominent psychiatric and behavioral problems, as well as painful dysesthesias. Scientists and medical professionals alike are unsure of its cause, commonly believed to occur due to spontaneous transformation of the proteins. CJD is untreatable and always fatal, with the death rates steadily climbing over the years (F.Morinet).
There are many obstacles to pinpointing a cure for Prion associated diseases. For example, although they are infectious agents such as viruses and bacteria, they lack nucleic acids, meaning that there are no currently established treatment options to use as a guideline for finding a cure.
One possible solution could be found in small molecules, like those in most prescription drugs, with multiple small research groups trying to find small molecules capable of providing treatment for Prions, and while no one has made any major breakthroughs, a lot of progress has been made.
One research lab discovered small molecules that helped with a low number of mice Prion strains; however it had no effect on any human strains (F.Morinet).

Another possible treatment is the use of antibodies. A research team was able to completely eradicate prions from infected cells in a dish, but the trials done on mice only produced results under certain conditions. The MRC unit in London has discussed the development of an anti-prion antibody, but no plans for testing in the near future have been announced.

Administering antibodies for a neurological disease faces another one of the many walls blocking researchers from a cure. Being as Prions attack the brain, most hypothetical methods present a risk of damaging the neural tissue even further. Any medical treatment to the brain requires crossing the Blood-Brain Barrier, a tight clump of cells protecting the brain from flowing blood. However, the MRC has found evidence that suggest the Blood-Brain Barrier may be able to be broken down in Prion patients.

The most recently proposed solution is the hypothetical and highly experimental “Gene Silencing” treatment, which suggests the use of DNA or RNA to temporarily turn of a specific gene. Theoretically, if the Prion Protein Gene were to be turned off the body would stop producing the Prions and effectively curing the patient, however it is very far away from becoming a reality in human patients

(PrionAlliance).
With better funding for larger, more professional research teams heavier steps can be taken towards finding a final solution to Prion diseases.
The road to a cure has been long and slow, from massive outbreaks in the 50s to Dr. Prusiner’s discovery twenty years later, to which doubt and denial that still lingers to this day. Even in our modern time with so many small breakthroughs, the answer still hangs outside our reach. But with a little hope, and little push, we can get there just a little bit faster.