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MRC Prion Unit
From fundamental research to prevention and cure

Drug treatments

A number of potentially useful drugs have been used in experimental animal prion diseases or in patients in an attempt to alter the course of the disease.  Four types of study have been done: those looking at abnormal prions in a test-tube, with cells infected with prions, in prion-infected animals or in actual patients affected by the disease.  Several drugs have delayed the onset of disease in laboratory animals if given before symptoms start, but none have halted or cured the disease once animals are unwell. 

There are only a small number of clinical trial reports of treatments tested to treat the underlying disease in CJD patients.  Most reports are anecdotal, often including details of only a single patient and very few have been conducted under strict conditions of doctor and patient being unaware of whether treatment or dummy pills are being given (known as a “double blind” study, considered the most rigorous way to test a drug).  Those reports of several patients usually contain a mixture of types of prion disease (for example, variant, inherited or sporadic CJD) on the assumption than an agent effective in one form of prion disease will be effective in other types.  This may or may not be true because the different types may have different sensitivities to drug treatment. Future trials may need to be conducted over prolonged periods of time, in different types of prion disease or in multiple countries. Each strategy for doing a trial has its advantages and disadvantages.

Information on studies  of the drugs quinacrine, pentosan polysuphate, tetracyclic compounds and flupirtine is provided below. 


The antimalarial compound quinacrine reduces the growth of abnormal prion protein deposits on infected cells in culture.  In contrast to the test-tube studies, experiments in mice infected with prions showed no effect of quinacrine on the incubation time.  Following anecdotal reports of improvement when taking quinacrine in a single patient with variant Creutzfeldt-Jakob disease (vCJD), two trials were initiated.  The PRION-1 trial was led by Professors Collinge and Darbyshire at the National Prion Clinic, UK.  Another trial based in San Francisco, USA, was led by Dr Michael Geshwind.  The headline results of PRION-1 were published in 2009 and unfortunately showed no survival benefit of quinacrine (Safety and efficacy of quinacrine in human prion disease (PRION-1 study): a patient-preference trial). The trial in the USA was similarly negative (Quinacrine treatment trial for sporadic Creutzfeldt-Jakob disease) and the drug is no longer being used.

Pentosan polysulphate (PPS)

PPS is a semi-synthetic chemical derived from shavings of beech wood.  It is used as an anti-coagulant in continental Europe when injected under the skin.  In the USA, PPS given by mouth is used for an inflammatory disorder of the bladder called interstitial cystitis.  There are several studies that have shown that PPS can delay the onset of prion disease in infected mice, and can cure infection in cells growing in culture.  PPS has been given to several patients with variant CJD and some with sporadic CJD in the UK.  In some of these patients PPS has been given as a direct infusion into the brain using a pump placed under the skin.  This was done because PPS is not expected to cross from blood into the brain because of its chemical properties.  Placement of the pump requires neurosurgery.  Although PPS has not been given in the context of a clinical trial, many of the treated patients in the UK have been visited by the same neurologist, Dr Ian Bone (Summary of Dr Bone’s report for the lay public concerning these visits). He concluded that,

  • PPS does not stop the progression of vCJD and other prion diseases.  Loss of brain function continues after treatment has started and, where measured by a series of brain scans, loss of brain tissue also continued.

  • The drug itself does not seem to carry a risk of serious side effects from prolonged usage at the modest doses given although one patient had seizures and two others evidence of bleeding into the brain.

  • Surgical complications of intraventricular catheter and pump placement occurred.

  • There remains uncertainty as to what precise dose should be administered to individuals.

  • Some of the patients treated with PPS appear to have survived for long periods.  However, it cannot be concluded that the treatment has had a beneficial effect, because it was impossible to make direct comparison with similar but untreated patients.  It is also very difficult to determine exactly when the disease starts and this obviously affects the estimation of survival time.

In Japan, use of PPS in patients with genetic or sporadic forms of prion disease has not shown any benefits to clinical symptoms, although as in Dr Bone’s report, there was uncertainty about whether survival might have been prolonged by the drug.

Tetracyclic Compounds

Tetracyclic compounds have also been studied experimentally.  The antibiotics tetracycline and doxycycline have been shown to lengthen the incubation period in experimentally prion-infected mice.  Tetracycline also reduces the formation of abnormal prions in test-tube experiments. Doxycycline has been studied by randomised clinical trials in Italy and Germany (Doxycycline in Creutzfeldt-Jakob disease: a phase 2, randomised, double-blind, placebo-controlled trial) however the results were negative.


The antipsychotic drug  flupirtine has been used in one moderately sized randomised clinical trial in Germany.  No survival benefit was seen, although the possibility of small benefits for thinking skills was raised by this study.  Further work was recommended with this drug but no clinical trials are active at present.

Symptom Control

A variety of specific symptoms, such as jerking of limbs termed myoclonus, behavioural or sleep disturbance, can also be supressed by drugs even though no survival benefit is expected.
Further information on symptom control is given here and here.

Potential Future Treatments - PRN100

There are several potential treatment options in the pipeline including agents that target the healthy form of the prion protein (PrP). There is substantial evidence for effectiveness and safety of antibody treatments which bind to PrP. Antibodies are proteins found in the blood and made by immune cells. They are used by our immune system to help fight infections. As PrP is one of the body’s own proteins we do not naturally make antibodies against prions. However we have been able to make antibodies in mice and then, by genetic engineering, make human versions of these antibodies. Antibodies that bind to PrP can cure prion-infected nerve cells growing in the laboratory. We think that the treatment works by removing the normal form of PrP required for prions to grow. Antibodies also have potent activity in animal models of prion disease, indeed if treatment is started early, before symptoms have started, the infection may be cured. PRN100 is a human antibody manufactured from the mouse antibody ICSM18. PRN100 binds extremely tightly to PrP. In prion-infected mice PRN100 can extend survival time from less than 200 days to a normal lifespan (>600 days), with these long surviving mice showing no evidence of prion infection when their organs are examined after death; essentially these mice are cured. As prion diseases may be transmitted between mammalian species, resulting in almost identical features, we have a high expectation that treatment will also translate well. PRN100 has now been manufactured in sufficient quantities to treat a small number of patients with sporadic CJD. We are currently making preparations to use this experimental treatment in the clinic.

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