Wednesday, 20 April 2016

Drug Repurposing Conference, Part 2, London - 29th Feb 2016

On 29th Feb I had the pleasure of going to the Findacure Drug Repurposing for Rare Diseases conference which was held at the Royal Institution in London.  My notes on this conference will take up a few posts. This is part 2 of 3. Part 1 is here. Part 3 is here.

The next presentation was by Dr Julie Vallortigara from Ataxia UK. Ataxia UK is a patient led research charity. the charity supports patients with a helpline, magazinr and leaflets, it had a network of people in branches, and arranges patient conferences and workshops. The Ataxia specialist centres are in London, Sheffield and Newcastle. The group raises funds to support a number of projects, specifically;

  • Improving diagnosis
  • Pre-clinical studies
  • Clinical trials
  • Symptom alleviation
There is collaboration between patient groups. pharma companies, clinicians and specialists. The group organised a conference in 2015 which was attended by 43 people from 20 countries. The conference was aimed at sharing knowledge/information/care/treatment and was viewed as a success.

The group are involved with two different drug repurposing projects. Patients with Friedrich's Ataxia, the most common type, have a mutation in the FXN gene which decreases the production of the protein frataxin. The research is testing if the gene can be switched back on to produce more protein. 

The first is for Nicotinamide or Vitamin B3. This has a good safety profile, and a phase 1 trial of 10 people showed promising results, and was reported in the Lancet ( the next stage is a larger trial and the group have been involved with giving the patient voice to the trial design. They are also providing some funding.

The second is for spinocerebellar ataxia type 3 (SCA3), and a range of drugs have been screened using animal models. There were two hits from the process, one of which was the anti-depressant citalopram, which was shown to improve motor function. The researchers are investigating a human trial with the groups help, and the group are also providing some funding,

The group also promotes; introductions to experts, advice on research, collaboration and funding, talks on ataxia and its impact, a patient registry, and recruitment to trials/studies.

Dr Michele Lufino of Oxford University the spoke next, providing an academic perspective on drug repurposing. He has been involved with the drug repurposing for Friedrich's Ataxia (FRDA). Friedrich's Ataxia gives rise to gait abnormalities, with age of onset 5-20. There are effects on vision, hearing and speech, There is no therapy at the moment and so the research is looking at stabilising the symptoms. They are looking at being able to increase the FXN gene in order to do this.

Dr Lufino reported a collaboration between Pfizer, who have a high quality library of small molecules, Oxford who have disease expertise and models, Imperial who are able to run a trial, UCL who have disease expertise and Ataxia UK who have the patients!

The collaboration between these means that there is a smooth and fast transition between identifying a candidate small molecule from the library to being able to run a trial. They are undertaking high quality science.

The speed is possible because  Friedrich's Ataxia is monogenic - it only affects one gene. Also the endpoint is known and there is knowledge on the cause of the disease.

Dr Lufino also mention the Oxford Rare Disease Initiative, ORDI:

Dr Nick Clarke of Pfizer spoke next with an industry perspective. Pfizer are looking to reposition themselves to have a greater involvement with rare diseases. They set up their own Rare Disease Research Unit (RDRU) in 2010, and they have 22 rare disease products on their books. However more recently they set up a Rare Disease Consortium in December 2013 which comprised Pfizer with leading universities, with the aim of making medicines.

They issue a call for projects and have one-to-one meetings with the applicants, this then leads to short expressions of interest, and then business plans.

Their first call was for neuromuscular diseases or haematology within certain disease classifications. This resulted in 400 applications. They were confident on 14 of these. which led to 10 plans, and funding for 5 projects.

Pfizer have around 3 million compounds in their library, and they are keen provide access to this to give compounds for research, and they are looking to collaborate with other companies to expand this number.

The process begins with the small molecule library. These are combined with biologics (genetically engineered proteins) and ideas (from the RDC) and converted into gene therapies (using genes to prevent/treat diseases), which can be turned into a product (medicine).

Some diseases have multiple mutations, and it is likely that products developed using the method would be for specific mutations.

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