Our First Winter Fund Raiser | Reanna7 | Page 2

Our First Winter Fund Raiser

Our First Winter Fund Raiser | Reanna7 | Page 2

Qingkailing

Qingkailing is a chinese medicine formula which has been used for cerebrovascular diseases and some inflammatory diseases including uveitis.    At one stage, about five years ago, there was some work in the US looking at the possibilities of using this for uveitis.  It is given as an injection and has a number of ingredients including some traditional roots and flowers.

There has been a recent trial at Shandong University of Traditional Medicine Eye Hospital where qingkailing was injected into rats with autoimmune uveitis (Birdshot is an autoimmune uveitis).  It was found that it could offer immunomodulatory effects.

If this is the case (it will need to be trialled on people too), it could be a possible alternative to the rather toxic systemic medications we currently have to take.

Read the full story at

http://www.ncbi.nlm.nih.gov/pubmed/23123470

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An Immunological Basis For Birdshot

We are so grateful to Dr Graham Wallace for writing the attached article, which explains the immunological process that leads to Birdshot.  Dr Wallace is a member of the Birdshot Research Network and is Senior Lecturer in Immunity and Infection at the University of Birmingham.  For those of you who attended the Birdshot Day in March 2012, you will remember that he gave a fascinating talk on ‘The Science of Birdshot’.  If you want to see his talk, we have posted it at:

http://www.youtube.com/watch?v=TNGAXyFrm00&feature=plcp

Here is Dr Wallace’s article on ‘An Immunological Basis For Birdshot’

The major histocompatability complex (MHC) is found on chromosome 6 in humans, and contains several genes which are involved in the immune response. Of particular significance are the genes that encode the human leucocyte antigens (HLA) which are fundamental to the immune system. HLA can be separated into two families: class I (A, B and C) and class II (DR and DQ). As class II molecules are not implicated in Birdshot I will not mention them again in the report. Each individual has two copies of HLA-A, B, and C on all cells of the body; one from their mother and one from their father. It is because of this genetic transfer from parent to child, that HLA class I were identified originally as transplantation antigens that must be matched for a successful tissue graft. The reason for this is the function of HLA class I which can be separated into two mechanisms;

(1)    HLA class I proteins present small pieces of proteins that have been broken up inside the cell on the surface and these are recognised by immune cells, called cytotoxic CD8 cells, which can kill other cells. This is particularly relevant for protection against viruses which enter human cells and replicate. Some virus proteins are broken down and presented by HLA class I.   That virally infected cell can be eliminated and the virus destroyed.

(2)    The second function of HLA class I is to protect normal cells from being eliminated by another group of cells called natural killer (NK) cells.  NK cells are also cytotoxic but do not recognise protein particles presented by HLA class I, as CD8 cells do. Rather, expression of HLA class I on a cell is recognised by protein called killer immunoglobulin-like receptor (KIR) on the NK cell and this interaction sends a “do not kill” signal to the NK cell and it moves on to check other cells. This benefit of this system is that some viruses cause HLA class I molecules to be removed from the surface of an infected cell thereby preventing recognition of viral fragments by CD8 cells. However such down-regulation of HLA class I will now make these cells susceptible to elimination by NK cells.

As HLA class I is found constitutively on all cells in the body they are not eliminated by NK cells. Bw4 is a region found on several HLA-B molecules.

KIR belong to specific families encoded by genes on chromosome 19 in humans. However, combinations of KIR vary between individuals and different cells may express more than one KIR. Both the inhibiting (KIRL), and activating (KIRDS) can be found on the same cell and it is the complex interaction of these molecules that control NK cells activation. (Fig 1)

Figure 1 – inhibitory KIRL recognise HLA class I molecules on cells and inhibit killing. Activating ligands induced by challenge are recognised by KIRS molecules. The balance between these signal determines outcome.

The MHC class I molecule, HLA-A*29, is associated with Birdshot uveitis.  KIR-HLA pairs implicated for weak inhibition such as KIR3DL1 + HLA-Bw4(T80)) in combination with activating KIR (KIR2DS2, KIR2DS3 and KIR2DS4) were found associated with increased risk in BCR HLA A*29 positive patients with BU. By comparison, association of strong inhibitory pairs such as KIR3DL1+HLA-Bw4(I80) in combination with KIR3DS1 was observed in HLA-A*29-negative controls. These results suggest that a profound effect of activating KIR (KIR2DS2/S3/S4) in the absence of strong inhibition may enhance the activation of natural killer cells and T-cell subsets against intraocular self-antigens, thereby contributing to pathogenesis of BCR.

To confirm the role of HLA-A2902 in the disease the gene inducing the protein was obtained from a patient with Birdshot and used to create a transgenic mouse. These animals did develop ocular disease that was similar to Birdshot, but not until 12 months of age confirming the effect of ageing on the condition.

Figure 2 – the reason why certain combinations of HLA and KIR are maintained is because they are useful at protecting against infections, but in combination with other gene polymorphisms this can lead to autoimmune disease.

The challenge in Birdshot as in many other forms of disease is to determine what the effect of the various combinations have at a functional level. ie do cells from patients with certain combinations “kill” less efficiently and what does this mean for the patients. It will also be necessary to analsye other genes for variants that may give an additive effect to the HLA:KIR combination and lead to disease.

 

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Clinical Trial on Ustekinumab

A single-centre pilot study is being undertaken in the United States to investigate the safety, tolerability and potential efficacy of subcutaneous injections of ustekinumab for uveitis.  The hope is, that if this drug works, it will have fewer side effects than the current protocol of steroids and immunosuppressants.

Ustekinumab is a human monoclonal antibody and is classed as a  ‘biologic’ drug.  It is currently used for people with psoriasis and some other conditions.

The study is due to complete in June 2013.  If this drug is effective, we will have yet another potential drug for Birdshot, for those people who find it hard to tolerate steroids and immunosuppressants.

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Helminth (worms) Infections

The Institute of Immunology and Infection Research at University of Edinburgh has published a paper on Helminth (worm) infections and host immune regulation.  It looks at countries and areas where helminth parasites are endemic (i.e. many people carry these worms all their lives) and note that in these countries, there is a very low incidence of autoimmune diseases and allergies.  This suggests that the helminth parasites may protect against your immune system becoming disregulated.

The paper points out that there is now much interest in investigating helminths as a therapy, in both laboratory models and in human trials.  They believe that understanding and exploiting the way these parasites work are likely to highlight new strategies to control both infectious and immunological diseases.

See the full text at:

http://www.ncbi.nlm.nih.gov/pubmed/23034321?dopt=Citation

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US Film Explores struggle of rare diseases

Two US filmmakers have produced a documentary on Hermansky-Pudlak syndrome (HPS), a rare disease.  This film highlights the issues faced by all of us with rare diseases.

Like Birdshot, very few doctors have heard of HPS, and no-one knows how many people have it.  Getting diagnosed is difficult, and finding some-one else with the syndrome is difficult, so it is a lonely path people tread.  They also point out that there are no disease specific medications (just like for Birdshot). We Birdshotters at least have an organisation (BUS) that lets us connect with other Birdshotters!

The film points out that whilst each rare disease is uncommon, if you take all rare diseases together, they are very common.  It also explores the way that patients, once diagnosed, connect with others.  They highlight a similar development to BUS for each of the rare diseases, and how the internet has helped in this.

The most interesting part of this film follows a parent of a patient with HPS as she tries to find other patients to participate in a clinical trial to test a new drug.

It is a really moving film.  To see the full article go to:

http://www.sfgate.com/health/article/Film-explores-struggles-with-rare-diseases-3924112.php

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Dexamethasone Intravitreal Implant

The Department of Ophthalmology at University Vita-Salute in Milan, Italy has published a paper on their experience of treating difficult, uncontrolled and severe cases of noninfectious posterior uveitis (Birdshot is a noninfectious posterior uveitis) with dexamethasone intravitreal implants on top of systemic steroids.  They found that, of the 12 patients they studied, all had decreased uveitis activity, increased visual acuity and reduction in the macular thickness after 9 months.  Three patients were able to reduce their steroids.  Only 3 of the eyes had an increase in intraocular pressure.  Their conclusion is that dexamethasone may be a promising additional treatment for patients with sever posterior noninfectious uveitis which does not respond to immunosuppressants.

See the full text at

http://www.ncbi.nlm.nih.gov/pubmed/23038070?dopt=Citation

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Access To Medicines

BUS was recently invited to participate in a debate on ‘How Can We Improve Earlier Access to Medicines for Patients in the UK?’  The debate was set up by Les Halpin, a very inspirational man who founded EMPOWER: Access To Medicine following his diagnosis of Motor Neurone Disease and realising that there were few medications licensed for this disease and that if research was undertaken on new medications, it would take many months or even years before  the medicine was available for use.

This debate was held at the King’s Fund in London and brought together a range of leading and influential individuals including:

▪   Lois Rogers, leading health journalist and contributor to publications including The Sunday Times, The Economist and New Statesman and consultant to the Department of Health and other government agencies

▪   Dr Richard Barker, Director of the Centre for Accelerating Medical Innovations, Oxford University and former head of the ABPI

▪   Yogi Amin, human rights and medical ethics lawyer, Irwin Mitchell

▪   Alastair Kent, Director of Genetic Alliance UK

▪   Professor Sir Peter Lachmann, Emeritus Sheila Joan Smith Professor of Immunology in the University of Cambridge and a fellow of Christ’s College

BUS has received a thank you letter for its input into the debate, which is copied below and gives information on how you can become involved in this campaign and how you can access the film of Les Halpin talking about the campaign:

Empower: Access to Medicine

I would like to personally thank you for attending the Empower: Access to Medicine debate at the King’s Fund last week. We appreciate your interest in and support for such an important subject.

I am very heartened by the response to this campaign. Whilst there are many separate discussions that are taking place on this issue, my main interest is in the voice of the patient which I believe has been least heard to date.

I am therefore delighted that patient advocacy groups from around the country have responded so positively. My key aim moving forward will be to support a unified patient voice so we can together deliver much needed change.

A longer and more comprehensive version of the film that was shown at the debate is now available online at www.accesstomedicine.co.uk and I would urge you to share this with colleagues and networks that may also be interested.

You can also join the conversation online through Twitter – find us on @empoweratm

The Empower team is now defining its campaign objectives as we continue to reach out to interested individuals and groups and we will keep you informed of our next steps.

In the meantime, if you have any questions or suggestions about the campaign, please contact Karen, James or Sarah at JBP on 0203 267 0074.

Yours sincerely,

Les Halpin

Founder, Empower: Access to Medicine