PRN100 frequently asked questions

Prion diseases and Creutzfeldt-Jakob disease (CJD)

Prion diseases are a group of rare conditions which affect both humans and animals. These diseases cause fatal damage to the brain.

There are three distinct causes of the human diseases:

  1. They can develop spontaneously for unknown reasons. This is called sporadic CJD (sCJD) and is the most common form of human prion disease.
  2. They can be inherited as a result of a faulty gene. This is known as inherited prion disease or familial CJD.
  3. They can be acquired as a result of exposure to prions in the environment. For example, variant CJD (vCJD) is acquired by eating food contaminated with BSE, a prion disease in cattle, and iatrogenic CJD (iCJD) is caused when prion infection is accidentally spread through medical and surgical treatment.     

Sporadic CJD is caused when healthy proteins, which exist normally in the human body, spontaneously become misshapen and form chains that build up in the brain.

These chains of misshapen proteins, which are called prions, stick to other healthy prion proteins causing them to become misshapen too.

This process repeats itself and the disease spreads through the brain.

This build-up of abnormal prion proteins causes brain cells to die affecting memory, thinking, talking, balance, movement and behaviour and eventually leads to the death of the patient.

There is no licensed treatment or cure for CJD. At present, caring for patients with CJD involves trying to keep the person as comfortable as possible and using medicines to reduce symptoms.

 

While a few patients may live for a year or more, most sadly die within four to six months of symptoms starting.

Approximately 120 new cases of sporadic CJD are diagnosed in the UK each year.  

Around one in every 5,000 deaths in the UK is due to CJD.

Sporadic CJD occurs at the same level in all countries so this equates to approximately 10,000 new cases a year worldwide.

PRN100 treatment

PRN100 is an artificially manufactured antibody which has been created in the laboratory.

CJD is caused when healthy proteins which exist normally in the human body become misshapen and build up in the brain. These misshapen proteins, which are called prions, stick to other healthy proteins causing them to become misshapen too and the disease spreads through the brain.

Our immune system produces antibodies to fight infections which invade the body. However, as abnormal prions are made of one of the body’s own proteins, our immune system does not make antibodies to fight them.

The PRN100 treatment is an artificially manufactured antibody which has been created in the laboratory and is given to the patient by a drip into a vein in the arm.

We believe the antibody works by binding tightly to normal proteins in the brain. This prevents abnormal prions from being able to attach themselves to healthy proteins, meaning that they cannot grow and cause devastation throughout the brain.

The treatment was given to six UCLH patients between October 2018 and July 2019.

Five of the patients had sporadic CJD and one had iatrogenic CJD.

The treatment was given as a slow infusion (a drip) into a vein in the arm over four hours.

The results, which are published in Lancet Neurology, show the treatment is safe and able to access the brain. In three of the six patients, disease progression appeared to stabilise when dosing levels were in target range. None of the six patients experienced side effects while receiving the treatment but all sadly died as a result of their condition.

We used all of the supply of PRN100 on the six patients who were treated between October 2018 and July 2019. The MRC Prion Unit at UCL is exploring options for the development of a clinical trial in the future.

Legal and governance arrangements

No it is unlicensed. The treatment was given to six UCLH patients between October 2018 and July 2019 under a “Specials” exemption.

 

A “specials” exemption permits a healthcare professional to treat an individual patient with an unlicensed drug when their special clinical needs cannot be met by a licensed product on the market.

The UK “specials” scheme is overseen by the Medicines and Healthcare products Regulatory Agency (MHRA) which has published a guidance note on the manufacture and supply of specials entitled The supply of unlicensed medicinal products (“specials”).

Three of the six patients were able to consent to receiving the PRN100 antibody themselves. The other three did not have the capacity to consent, so with the support of their families, we sought the opinion of a judge in the Court of Protection in order to proceed.

UCLH provided the PRN100 drug to patients under a “specials” exemption, rather than a regulated clinical trial.

In order to provide this treatment to patients, UCLH created a PRN100 oversight committee, independent of the MRC Prion Unit at UCL and treating clinicians.

Our senior leaders, and world-leading clinicians and researchers, many of whom hold joint positions with our academic partner, UCL, were committee members.

They were joined by external experts in prion disease, lawyers and patient advocates from the charity Cure CJD Campaign.

The group considered the numerous and complex clinical, safety, legal and ethical issues arising from the potential use of this unlicensed treatment for CJD.

A sub-committee of this group, comprising senior clinical leaders, monitored the clinical team’s decision-making throughout the treatment programme. The sub-committee had to approve the clinical team’s decisions about dosage levels before treatment could progress.

Approval from the MHRA was not needed because this was an NHS treatment, using an unlicensed drug, provided under a legal “specials” exemption. This was not a clinical trial.

However, we discussed the proposed use of the treatment with the MHRA and they confirmed that our plans were appropriate and in keeping with their guidance.

Stakeholder organisations

The Medical Research Council (MRC) Prion Unit at UCL (University College London) is a national centre of excellence for research into prion disease.

It was established in 1998 at the request of the Government to tackle public health problems caused by prions and to develop treatments.

The Unit is core funded by the MRC but integrated within UCL.

 

The National Prion Clinic (NPC) is the NHS national referral centre for prion disease. It is part of University College London Hospitals NHS Foundation Trust (UCLH).

The NPC is funded by the NHS to provide diagnosis and care for patients with, or suspected to have, any form of human prion disease.

Around 120 patients a year with sporadic CJD are referred to the NPC. The NPC also cares for most families with inherited prion disease and acquired prion diseases.

The clinic works in partnership with the MRC Prion Unit at UCL.

 

UCLH provided the treatment to six patients between October 2018 and July 2019.

Researchers at the MRC’s Prion Unit developed the treatment. On 1 June 2017 the Unit transferred to University College London (UCL).

Researchers at the MRC’s Prion Unit developed the PRN100 antibody as a potential treatment for patients with prion disease.

The manufactured product belongs to the MRC.

The MRC provided the PRN100 antibody to UCLH for use in patients with prion disease.

We would like to extend our thanks to the National Institute for Health Research (NIHR) UCLH Biomedical Research Centre, the JP Moulton Charitable Foundation and the Cure CJD Campaign charity for their support in the development and use of PRN100.

Further information

Please contact the National Prion Clinic (NPC) team on 020 7679 5142 or email uclh.prion.help@nhs.net

The Cure CJD Campaign charity has produced the following useful video explaining prion disease and the PRN100 treatment: https://www.curecjd.org/research

You can read a news story about the results of treating six UCLH patients with the PRN100 here

The Lancet Neurology paper is available here