Breakthrough for Pulmonary Hypertension Treatment

Last year there was a significant breakthrough in the genetic research into Pulmonary Arterial Hypertension (PAH) being led by Professor Morrell at the Cambridge Biomedical Research Centre. Professor Morrell is both British Heart Foundation Professor of Cardiopulmonary Medicine and Research Director, National Pulmonary Hypertension Service at Papworth Hospital.

A protein was discovered that targets the effects of and reverses the damage caused by a faulty gene BMPR-11 - this faulty gene is the main identified gene for causing inherited Pulmonary Arterial Hypertension. I have put the links for more detailed information on the research project and on the breakthrough discovered last year below.


The Genetic Research Project


BHF Press Release 2015


This week it was announced that Morphogen-IX, a new Cambridge based biotech, has gained seed funding to develop a new treatment for PAH, following on from the findings last year. This drug will directly target the disease and has the potential to provide the first disease modifying approach to the serious life limiting effects of PAH. The current therapies for PH and PAH help to alleviate symptoms, but as yet there are no medical options to modify the course or outcome of the disease. The company will be solely dedicated to developing a therapy that will tackle the disease rather than just manage its symptoms and they have received grants of 1.5 million to develop the drug. The link below gives more information on Morphogen-IX


Morphogen-IX


This is marvellous news for the Pulmonary Hypertension community - we always live in hope that a breakthrough will happen and that eventually a cure will be found. When a person is diagnosed with PH it is both shocking and life changing. Whatever stage of PH you are in, you know that you face a long journey of hospitals, doctors, tests and treatments. The treatments for PH vary depending on the type of PH and the stage of severity that the PH is in - they vary from oral medications to complex inhaled medications and intravenous medications, which are very daunting to face. There are some surgical alternatives for some patients such as Pulmonary Endarterectomy, Lung Transplantation or Heart and Lung transplantation - high risk surgeries that again can feel terrifying to face. For some there are no surgical alternatives, just therapies that manage the symptoms, although the disease progresses. There is also the knowledge that PH can be a life limiting disease and that you face a future that is uncertain and with some disability.

To know that there is research and development of a drug which may reverse the effects of this devastating disease is wonderful news. These new developments bring so much hope to so many. Hope that they may not have the future they are presently having to face - one of complex drugs, surgeries and one that is potentially life limiting - and hope for a future that could change for the better.

The announcements that this new drug is going to be developed demonstrates great progress has been made with the genetic research. The new drug will then need to be put through the various clinical trials. We wait in hope for more announcements when developments reach this stage. In the meantime there are other drug trials in progress, where it is hoped that symptoms in patients may be helped and controlled better and again, even modified. One is a trial for Tocilizumab, which is currently used for arthritis and it is hoped it may modify PAH too. Again more hope. A link for more details on this is below.

New Clinical Drug Trial

On a personal note, although I don't have PAH any more after undergoing a heart and double lung transplant as an end stage treatment, I'm delighted there are these new developments to help PH sufferers and that there is some hope for the future. I have a keen interest in the genetics research as I underwent genetics testing and took part in this genetics research at the very beginning of the project. I still take part in the research and last year gave more DNA as the project moves on forward and I was given information about the possibility of second generation testing, so it is still of great interest to me. It was an honour to take part in the publicity process about the genetic research and the breakthroughs that are happening over this last week.


















My story and involvement with genetic

This week I had the opportunity to take part in an interview with BBC Look East and on a fun note the pictures show my new puppy, Ted making his TV debut in his first ambassador role for PH! Visit my author Facebook page and scroll down to find the whole interview with BBC Look East, Professor Morrell, the research team, Ted and me.

Life is for the Living Facebook page


The 1.5 million funding raised for the new drug will now build on the work of the project funded by donations from the British Heart Foundation. The funding from BHF is vital in developing this research. Their link is below.

British Heart Foundation

We live in hope!

Hope and Breakthrough News for PH!

I'm still involved with a genetics study to enable a better understanding of PAH and enable better treatments. Although I don't have PAH any longer following my heart and double lung transplant it is still possible for the research team to use my DNA samples, so I'm still giving blood samples from time to time. The genetic thing first became all important to me because I literally had no idea why I had PAH and was scared that my two girls may have it.

My PH team kindly referred me to Addenbrookes and although there was no formal testing for PH genetics at the time, I was lucky because they were about to establish one and establish the research into understanding the genetics of PH in the hope of getting some breakthrough for new treatments.

Filming with BBC Look East

When you're diagnosed with PH it is a very frightening time, no matter what stage your PH is in. For me,  I was in end stages, so I was put on intravenous medication within a few months then referred for a heart and lung transplant. I was told I wouldn't have long to live and perhaps only have two years of quality life left and then in the same breath told it may take up to two years or more to get my transplant. It was a stressful and scary time. With the shortage of organ donors, it is a very difficult to get three organs. Organs can be split to save two or three lives instead of saving one and only a couple of transplant centres still commit to undertaking them - I was lucky - lucky in so many ways.

Sometimes during my life I've complained I've not been in the right place at the right time: the sun shone on me through my illness though - I was being treated in a centre that believes if you need three organs then that's what they will strive to get for you and I was under a transplant team who had a lot of expertise for this rare operation. I was also lucky I was under the excellent care of a superb specialist PH team and they knew exactly what to do every time I met a crisis and saved my life more than once. I was more than blessed on that day I received my transplant, that day a family said 'yes' to organ donation and that my donor had believed in organ donation. It is all a very hard route to go down though, however blessed you are - and I know for some this route is even harder. For many even transplant isn't an option for various reasons.

When you are first diagnosed with PH, it doesn't really matter what stage of PH you are in: mild, moderate, severe ... it is all very frightening. You know it is a chronic and incurable disease and it doesn't matter how well you are doing or how positively you manage things, the fear is always there about the future. You know the disease may progress, then you will need more treatments ranging from oral medication, oxygen to intravenous medication and then for some more complicated and life threatening surgeries such as Pulmonary Endarterectomy, lung transplant or heart and lung transplant. You fear a future of disability and you are afraid of dying and your family are terrified what will happen to you and them next.

Even undergoing the life threatening surgeries to remove PH, a cure as such isn't truly found. Often with a Pulmonary Endarterectomy, there are still remnants of PH and distal blood clots, which require life long management and drugs and with a lung or heart and lung transplant the survival rates are only 50% at two years. I was also informed I would have a 20% chance of not surviving the operation or the first year after my heart and double lung transplant. It is a hard route to be faced with and all any family, who has been affected by this disease, wants is to know there may be a cure - know that somebody somewhere is doing something to help them, something that may save their future.

Last week I was contacted by the British Heart Foundation, who have provided funding for research in the genetics of PAH and was informed there had been a breakthrough in the research. The research is being undertaken by a team led by Professor Nick Morrell at Cambridge, who is both a Research Director for the PH service at Papworth Hospital and a British Heart Foundation Professor of Pulmonary Medicine. 

A protein, BMP9 has been discovered that can counteract the damage that is done by PAH to the cells in the blood vessels of the lungs: it can prevent narrowing of the blood vessels and also restore damage. The research has found that patients with PAH don't make enough of this protein. Tests carried out have shown that it is easy to manufacture and therefore could possibly restore the blood vessels in patients lungs to a healthy condition. 

More testing, research and patient trials have yet to be done and it will take some time yet, but this is a major breakthrough for the treatment of PAH, both inherited and idiopathic and hopefully if things come to fruition, then for patients with secondary PH too. This news brings so much hope for patients who are suffering with PH and facing difficult choices about treatment in the future and so much hope that anyone being diagnosed in the future will have chance to be cured and not face the long and gruelling route that patients must endure now. 

I was asked if I would help with the media launch of this breakthrough, as I've been involved with the genetic research and suffered with end stage IPAH and the difficult treatments. On Tuesday, I was interviewed live on BBC Three Counties Radio talking about what it is like to live with PAH and how this research breakthrough is such a significant step for patients suffering with it. On Wednesday, reporters from BBC Look East visited our home and interviewed me for an article for the 6.30pm and 10.30pm news later that day. I was delighted to help, not only to share the promising news that gives families so much hope, but to raise awareness too of what this cruel disease is like to live with and the difficulties of the treatments we have to face. Also, PH is regularly misdiagnosed, so to be able to explain its symptoms on TV and radio, could possibly alert someone to the condition - the earlier a diagnosis, the better the prognosis.

News Reports

British Heart Foundation Press Release

Cambridge University Research


BBC Three Counties Radio 16th June 2015  (just past half way through)


BBC Look East Report 17/5/15

Article in the Guardian news 21st June 2015

The hope of a cure is something anyone diagnosed with or affected by this disease hopes for everyday and now things look like they may be getting nearer ... I truly hope so - it would be such a wonderful thing.

A Peek around the Path Labs

Ever wondered, as a regular hospital patient, what they get up to with all those endless blood and tissue samples that the doctors keep taking? Well it isn't every day that you are offered a chance to have a guided tour around the pathology labs of your hospital, but then again Papworth Hospital is no ordinary hospital being a world renowned and leading heart and lung hospital. Thanks to Michelle, who runs the Papworth PH Matters Support Group and Dr Mark Southwood a post doctoral researcher at Papworth, a tour of the pathology labs was arranged for our group. I've tried my best to be accurate in my account of what I saw, but I am no scientist, so I apologise now if I've got something wrong, there was so much to learn and see and take in!

Our first stops after being welcomed was the 'Cut Up Room' and the 'Main Laboratory'. Fortunately, no, nothing gory was going on here as we all went through to our first port of call with some trepidation, hearts and lungs being chopped up kept springing into my mind! In here it was explained to us how all specimens handled are assigned a unique pathology number to keep track of them. Tissue samples are examined and dissected and placed in small cassettes, where they are bathed in a fixative ready for processing. The fixative hardens the tissue and prevents the proteins within the cells from degrading. The tissue can then be saved forever. After the tissue is hardened it is ready for the processing machine, which takes about eight hours or so to dehydrate the tissue.

Next on the tissue is embedded in hot wax to form a tissue block and then thin slices of tissue using a cutting instrument can be cut. They are then stained with Haematoxylin and Eosin and then they are ready to be examined on a slide under the microscope. We got chance to examine some tissue slides under the microscopes in the main laboratory.  I couldn't help getting the feeling after teaching primary school science for many years that here is proper, real life, exciting science going on before my eyes!

Next on the agenda was the Immunohistochemistry, Immunology  and research rooms, now we were really getting to the cutting edge of science and we got to see how relative to PH the research in these rooms was too. Sections of the tissue block are treated with antibodies to the specific proteins the researcher may want to test and the slides develop a brown colour when the designated antibody is detected and then it can be detected on the slide where the identified protein is present. We were introduced to flow cytometry, a technique for counting and examining microscopic particles such as cells and chromosones and is routinely used in the diagnosis of health disorders.

It was explained to us about all the different types of research being undertaken including using tissue banking, cell cultures and luminex analysis, all providing a spread of information relative to various diseases and research projects. There is research going on into cytokine signalling in PH and link up with Professor Nick Morrell's team at Cambridge University and the research they are undertaking there on genetics. As Papworth Hospital is a specialist heart and lung hospital, they often have referrals for their expertise from other hospitals.

We went on via the freezer and tissue store areas to the Haematology and Blood Sciences Laboratory, here we were given a talk about how they tested the blood samples and were shown the equipment they use. It was interesting to find out that this department was located at Papworth, but belonged to Addenbrookes. The Papworth site do the more routine blood tests and operate twenty four hours a day and all other blood samples are sent to Addenbrookes for analysis. As well as undertaking the blood sampling, this lab is also responsible for managing the blood stock for blood transfusions that are needed during some of the major heart and lung operations that take place at Papworth. We were shown some examples and shown how it was all stored. I couldn't help asking how much blood they would normally prepare for a major operation, having my transplant operation springing to mind, as I have already prepared and signed the forms to consent for a blood transfusion. The answer was that they usually prepare three bags of blood in readiness, but obviously it is variable.

Last but not least was an optional visit to the mortuary, I'd already decided to opt out of this one, but everything was so interesting and staff so accommodating that when it came to it, it felt like a natural close to the tour. So in for a penny, in for a pound, off we went. We were shown through the family waiting areas and into the the autopsy room. The key emphasis on this part of the tour was how staff gave their utmost respect, care and sensitivity to the deceased patients and their families.

After a busy lunch break back at the library halls, Doctor Southwood then kindly gave us a talk about the research of pulmonary hypertension. and explained in detail the types of information they have been able to gather following analysis in the labs of tissue samples taken from patients who had had Pulmonary Endarterectomy operations and transplant operations and also how this links in with the research work being undertaken by Professor Nick Morrell at Cambridge University in conjunction with all the other specialist PH centres.

All in all it was a very busy day, full of new and interesting information, it really opened my mind how all the information gathered at Papworth comes together to make a centre of expertise that also informs other hospitals and many internal and external research projects. I was also really encouraged at how much work is being done to try and find out more about our disease. Now there is no mystery surrounding what happens after our blood and tissue samples are sent for testing, it has become a tangible thing, we can put faces to the people and we have seen all the equipment, know the processes and all their stages.

On a very personal note I was most interested to hear how much the tissue sampling can help add to the bank of information held on PH and on the funny side I cannot help thinking that one of the first things I will be saying when I wake up from having my heart and lung transplant operation is, 'did you get that bucket with my old heart and lungs in across to the research team?'

I would like to thank all the staff at the pathology and haemotology labs for making us so welcome and being so helpful and all the staff who worked hard behind the scenes to prepare for our visit.

Papworth PH Matters Support Group: next meeting is Saturday 7th September in Papworth, Library Hall. Michelle has arranged for researcher Amer Rana from Cambridge University to talk to us about the latest research going on for PH. The support group makes everyone welcome and is for anyone affected by PH, patients, families and friends. You do not need to be a Papworth patient to attend. 
 
  

Warfarin Time

I have my next appointment with the nurse at the INR clinic next week. Now some of you wonder what INR stands for. Look it up on Wikipedia and you will find various connotations: Institute of Nuclear Research; the currency code for the Indian rupee and the Institute of National Remembrance to name but a few. In my world of Pulmonary Hypertension and the rest of the medical world it stands for 'International Normalised Ratio', which is a laboratory test measure of blood coagulation based on prothombin time. In plain language how thick your blood is and how quickly does it clot. Patients with any type of Pulmonary Hypertension are prone to blood clotting, which in itself can be catastrophic to health and life threatening and therefore many of us have to take the drug warfarin, an anti-coagulant drug, and have our INR levels monitored closely. INR levels have to be watched carefully as if your blood is too thin, it can cause internal bleeding and if your blood is too thick it can cause blood clots, both very dangerous conditions.

There are many PH patients who have developed PH because of undiscovered blood clots in their lungs and for them the importance of an INR test is paramount. Many of these PH patients are suitable for a Pulmonary Endarterectomy operation, which is a major high risk operation to clear the blood clots, but if the operation is successful it can lead to improved quality of life and increased life expectancy. Papworth Hospital in Cambridgeshire is currently the only centre in the UK that can offer this surgery. Recently this operation was featured on the 'One Show'. You can find this on YouTube, just google Pulmonary Endarterectomy and the link will come up - the link would not work in my blog unfortunately. It does not always return life to normal though for some patients and they still have PH through residual and distant clots and have to have the general and specialist PH drugs and warfarin to help them. There is more about Pulmonary Hypertension caused by blood clots and the treatment available on the PHA UK website below:

www.phassociation.uk.com

I am not in as much danger as my PH friends who have blood clots, however I am possibly prone to blood clots just by having PH. I have to have an INR measure between 2 and 3 to keep my blood thin enough so it doesn't clot, but not too thin that it poses the danger of internal bleeding. My warfarin dosage is adjusted accordingly to keep me as safe as possible from all the risks involved, hence my regular visits to the INR clinic. This INR range may vary from patient to patient depending on their condition and classification of PH. 

When you are first put on warfarin you are given a full set of instructions about your diet. Basically you need to keep your diet steady as INR levels can be affected by diet, vegetables containing vitamin K and alcohol can cause warfarin to be less effective, so whatever you are used to having, if you change things dramatically than you may put yourself in danger. For example if you have one glass of wine every now and again and then decide to drink two bottles on a Saturday night not only will you get drunk, but your INR will be out of range. Decide to have spinach for your breakfast, lunch and dinner, when you only usually have it once or twice a week, then you will put yourself in danger and drinking cranberry juice is a no no! Warfarin doesn't really inhibit your diet though once you get used to it, it is the usual thing, eat a well balanced and steady diet and all should be reasonably fine. Warfarin can also interact with other medicines, so any doctors and pharmacists that you deal with need to aware you are on it. 

I am prescribed warfarin in packets of half mg, 1mg, 3mg and 5mg and as the dose is adjusted now and again I can just make up the new dosage with this assortment I have in stock. They are colour coded so that you don't mix them up incorrectly and get them confused and accidently overdose. 

I am really grateful and lucky that I have my INR tests at my local doctor's surgery, which is just a few hundred metres away from my house. When I first started on warfarin, I had to go to my local hospital for the blood test and the pathology department was always packed and there was usually at least two  hours to wait if not longer. I obviously had to pay expensive car parking charges and needed someone to drive me and accompany me. At the time I had to do this, the hospital was undergoing refurbishment, which meant a long uphill walk from a temporary car park. This was also when my PH was at its worst and I was struggling to walk and passing out regularly. 

Many of my PH friends have to endure the struggle to and from the hospital though and have different people attending them each time they go. It seems a post code lottery as to how the system works in different parts of the country and how much very sick people are forced to endure all in the name of a blood test.  My late father, who had end stage heart and lung failure, was on permanent 24 hour oxygen to breathe and was confined to a downstairs room for the last year of his life, had to endure going to hospital every week for his INR check. He had to wait about two hours each time for the 'always late' ambulance to pick him up, wait the hours of waiting for the blood test and then wait hours again for an ambulance to take him back. Having to go through all that each week absolutely beggars belief when all it takes is a prick of your finger and a drop of blood on a slide, why on earth the nurses attending him each week at his home couldn't do it I will never know, my mum could never get a proper answer on that one. So I know I am blessed at the moment when it comes to my INR checks.

Some of my friends have gone to the expense of buying their own INR machines to save them the grind and inconvenience of extra hospital visits, but these are expensive and still need to be used in conjunction with your local warfarin clinic and GP.

So I'm lucky now and I have also had the the same lovely nurse who helps me each time I go, which is another bonus. She says I'm one of her most interesting patients as she has never had a patient with Pulmonary Hypertension before or a patient waiting for a heart and lung transplant. I think I am also about twenty years younger than most of her patients, so she enjoys a laugh and chat! Many of her patients are elderly and usually have blood clots or atrial fibrillation. 

I have to carry a little 'yellow book' and card with me at all times, so that if I ever need emergency medical attention, the medics will know that I am on anti- coagulants. 

I usually have to go every two or three weeks for my INR check, but since I was ill before Christmas, my INR range has been all over the place. First it was too high, meaning I was in danger of internal bleeding, a few days later in hospital it was too low meaning I was in danger of blood clots and then, with good timing and great inconvenience for us Knebworth warfarin patients, Christmas and New Year fell on a Tuesday our clinic day. This meant I would be struggling to get another INR check before Christmas and for the next couple of weeks to make sure I was back in the correct range again. 

My absolutely fantastic warfarin nurse, on getting the message I was in hospital phoned our home and left a message of all the times I would be able to contact her over Christmas to get an INR check done out of the usual clinic times. She only comes to our surgery once a week, but her main job is as a practice nurse in another surgery, in another town; however, she made time to to see me on Christmas Eve when her surgery at her usual doctor's was finished, so I would be safe over the festive period. She goes an extra mile every time and it is wonderful to have such strong support when something is worrying you. Bank holidays are always a big worry when you are seriously ill as that is always the time if something is going to go wrong, it will go wrong! 

Getting used to warfarin was a bit of a shock at first and tiresome, with all the blood tests at hospital and the diet worries, but with all my warfarin nurse's help and support now it's just become part of my natural routine in life.            

     

Just one last fact about warfarin, it is a commonly used rat poison, it was first used as a rodenticide in the 1940's, so if we ever get rats in our household, they better watch out, there are copius amounts of warfarin about! 

    

I would be interested to know what others have to endure with their regular INR checks and whether your stories are good ones like mine or bad like my dad's!

Join the organ donor register: https://www.organdonation.nhs.uk/

Sign the epetition for the opt-out scheme: http://epetitions.direct.gov.uk/petitions/38220