Since April 2008 the Patient Support Group has organised five meetings, all members receive minutes and agenda of these meetings. These were held in the Alpha One Foundation’s office located in the RCSI Building at Beaumont Hospital. This venue can be changed at any time as organised by the group. Items discussed range from awareness to feedback of delegates to international patient meetings e.g. Prague in May 2008. Attendance has been low recently but we hope to improve this with an awareness campaign in October 2008. We would encourage patients to keep in contact with other patients and we hope to develop a newsletter updating members of news events and patient stories.

Fundraising
Women’s Mini Marathon June 2008 Fundraising from the Women’s Mini Marathon in June 2008, being presented to the Alpha One Foundation from Anna Cassidy and her family. Staff from the RCSI, Beaumont Hospital and Alpha One Foundation participating in the Women’s Mini Marathon in 2009.

European Alpha-1 Conference, Rome 2007 

Delegates from 21 countries world wide gathered with fellow patients, carers, medical experts and pharmaceutical company representatives in the Eternal City for the 3rd Alpha 1 Patients Congress, hosted by the Italian Alpha-1 Association, on the weekend of 28th-30th September, 2007.  The Alpha One Foundation had 2 representatives present at the Congress, myself and John Hannan.

The Conference began on the evening of the 28th, when the assembled delegates and guests were welcomed by Larry Warren, our own CEO and President of Alfa Europe and Nuccia Gatta, President of the Italian Alpha-1 Association and Vice President of Alfa Europe.  At this stage Larry gave a warm welcome and thanks to the Medical Professionals, who were attending the Conference, for their continued care and support, also to the Pharmaceutical Companies for their support.
Larry Warren reported that the Alfa Europe Federation was now a legally recognised and registered organisation. It will be an organisation of many languages and cultures, and it is hoped will prove to be a voice in the EU that will increase awareness of Alpha-1 and promote more, much needed research into the illness. To open the Conference all the Delegates we asked to give a brief presentation to show how their individual patient groups were working and how they were moving forward. 21 countries were represented, including for the first time the Czech Republic, who have only recently set up an AATD centre. In addition to European countries there were delegates from the USA, Puerto Rico, Argentina, Australia and New Zealand. Some countries have had patient groups for a number of years while others have only recently been formed. Patient groups were proactive in many aspects of their organizations, such as the setting up of support networks for patients, regional groups, supporting research programmes, advocating for clinical trials, working closely with the medical professionals, and producing leaflets and newsletters explaining about Alpha-1. Saturday began at 9am, with a presentation from John Walsh, President of the Alpha One Foundation in the USA, entitled “Patients Empowerment”. This talk proved to be very motivating. John first said how encouraging it was to see so many countries sending delegates to the conference. He said that patient groups give alpha-1 patients  

    * Inspiration through collective and shared experience
    * Courage to do things
    * Empowerment to take action, through frustration and desperation
    * Self confidence and power
    * Alphas serving Alphas

Patients groups involve not only patients but loved ones, wider groups, communities, medical professionals, scientists, and also challenge patients to get up and become involved, and can encourage healthcare industries to aid research into therapies. Continuing with his presentation, John said how he had picked up common themes from all the delegates-

    * Lack of awareness, low detection rates and diagnosis
    * Lack of resources
    * Limitation on access to therapies in some countries
    * Start up Charities
    * Limited or no support for patients
    * Transplant issues
    * The more aware the better the cure
    * Quest for a cure(s) to conquer or eradicate the illness

The one message that came through is that there is under diagnosis, mis-diagnosis, and a lack of awareness and understanding amongst the medical profession and the general public of Alpha-1. It is patient groups who can change this, by making sure hospital consultants, GPs, nurses, family and friends know about the illness and the effect it has on people’s lives, not just sufferers, but their carers and families.  

Josephine McGuirk, October 2007.  

Abstracts from Rome Conference 2007

ALPHA-1 ANTITRYPSIN DEFICIENCY: WHERE WE ARE, WHERE WE ARE GOING TO

Maurizio Luisetti, Center for Diagnosis of Inherited Alpha-1 antitrypsin Deficiency, Laboratory of Biochemistry and Genetics, Institute of Respiratory Disease, University of Pavia, Fondazione IRCCS, Policlinico San Matteo, Pavia, Italy

At the beginning of the 1960s, two scientists in Sweden, Laurell & Eriksson, associated missing bands on paper electrophoresis in sera with subjects suffering from pulmonary emphysema and chronic liver disease. This was the first report of a disorder since then referred to as “Alpha-1 antitrypsin Deficiency” (AATD). Now, 44 years after the discovery, AATD is in its middle age, and an astonishing amount of data have accumulated during four decades. We have currently a satisfactory view of the AATD epidemiology, at least in western countries; we have gained a good level of knowledge about the pathogenesis of lung and liver disease. We have developed suitable methods for laboratory identification of protein and molecular abnormalities linked to AATD. A number of national registries for AATD have been established, as well as national patient support groups, and their federations work together for a better awareness of the disorder. Replacement therapy is available in a growing number of countries, and several hundreds of AATD subjects with lung disease are currently treated. But a number of relevant questions are still unanswered, and we hope we are able to offer satisfactory answers to these question in the next future. Basic questions, such as the definition of the exact ratio between asymptomatic individuals affected by AATD and individuals affected by AATD which develop lung/liver disease (and, more importantly, what differentiates the latter from the former), and clinical questions, such as the development of more effective “replacement” therapies, are among the questions AATD patients ask the scientific community. This is a commitment for the future.
 
PATHOGENESIS OF LIVER INJURY IN ALPHA-1-ANTITRYPSIN DEFICIENCY
F. Callea, Department of Pathology, Children’s Hospital Bambino Gesù, Rome, Italy.

Liver pathology is a major manifestation of Alpha-1-antitrypsin deficiency (AAT), restricted to the AAT mutations causing misfolding of the protein and accumulation in the Endoplasmic Reticulum (ER) of hepatocytes. So far three such mutations have been identified, Z, Mmalton, Siiyama, the Z variant being the most frequent. The spectrum of the associated liver pathology comprises neonatal cholestasis, chronic hepatitis, cirrhosis and HCC. The mechanism of the liver damage is not fully understood. There are two major lines of thinking: 1) the storage is toxic per se, 2) additional factors are required for the development of the liver damage. The main argument favouring the second opinion is mainly based upon the observation that only a minority of AAT deficient individuals develop liver disease. I would like to emphasize the point that the accumulation of the mutant AAT represents per se the elementary lesion of the disease and that is an unavoidable process. In this context I will be reviewing the patho-morphogenesis of the storage phenomenon and the main morphological alterations with special regard to new electron microscopic findings. The epidemiological and clinical relevance of the morphological alterations are discussed also in view of the new experimental data on the pathways for degradation of the mutant proteins that accumulate in the ER.

PATHOGENESIS OF LUNG DISEASE
David A. Lomas, University of Cambridge, Cambridge, UK.

Alpha-1 Antitrypsin is produced from the liver and bathes all the tissues of the body. Its role is to protect against tissue damage from enzymes released from neutrophils. The genetic deficiency of alpha-1 antitrypsin that results from the Z mutation causes the protein to form polymers that are retained within the cells of the liver. This retention of protein causes liver disease. The resulting lack of plasma alpha-1 antitrypsin (10-15% of normal levels) leaves the lungs exposed to attack by neutrophil enzymes and so results in emphysema. We have recently shown that some of the alpha-1 antitrypsin that enters the lung can change shape and form chains of polymers. These polymers are unable to function as inhibitors of neutrophil enzymes and so exacerbate the tissues damage. Moreover the polymers are themselves inflammatory and cause further attraction of neutrophils into the lungs. This in turn accelerates the inflammation and emphysema. All these factors are exacerbated by smoking. My laboratory has defined the pathway by which polymers form and is currently developing strategies to block the polymerisation of Z alpha-1 antitrypsin. Such a strategy will prevent the accumulation of Z alpha-1 antitrypsin within hepatocytes thereby treating the associated liver disease. The release of alpha-1 antitrypsin from the liver will increase the circulating levels of alpha-1 antitrypsin and hence provide protection for the lungs against emphysema.  

THE NEED OF STANDARDIZATION OF DIAGNOSIS
Ilaria Ferrarotti, Fondazione IRCCS, Policlinico S. Matteo, Pavia, Italy.

AATD is a largely under-recognized condition and one of the most common severe hereditary disorders in the world. To improve the diagnostic yield and to address the discrepancy between expected and diagnosed AATD cases, the recently published ATS/ERS Statement (2003) recommends diagnostic testing for all symptomatic adults with emphysema, COPD or asthma with incomplete reversible airflow obstruction, individuals with unexplained liver disease, asymptomatic individuals with persistent obstruction on pulmonary function tests with identifiable risk factors (cigarette smoking, occupational exposure) and adults with necrotizing panniculitis. The laboratory diagnosis of AATD has evolved from the initial description of the condition in 1963 based on paper electrophoresis – agar-gel electrophoresis – immunoelectrophoresis to the currently used methodology, that is a combination of serum AAT level determination, isoelectric focusing (IEF), genotyping, and sequencing. The availability of matrices such as the dried blood spot have facilitated the implementation of laboratory analyses for alpha-1 antitrypsin deficiency, but have also challenged laboratories to develop more reliable and reproducible techniques starting from dried blood.

THE IMPORTANCE OF SCREENING
Luciano Corda, Centro Riferimento Deficit Alfa1-Antitripsina, Medicina Respiratoria/Prima Medicina, Spedali Civili, Brescia, Cattedra di Malattie dell’Apparato Respiratorio, Università di Brescia, Italy.

Screening is performed to identify the presence of a disease or a risk factor for a disease, typically among asymptomatic persons. In this way, a disease, or risk factors for a disease, can be detected early, allowing either early treatment or prevention. Screening tests are widely used by clinicians as part of the periodic health examination, as well as by public health officials. Examples of screening tests are as varied as blood tests to detect lead poisoning in young children, mammography to detect breast cancer and questionnaires to identify persons with alcohol or other drug problems. Even if alpha-1 antitrypsin deficiency (AATD) is considered a rare disease, it is probably the most common widespread genetic abnormality. AATD is rarely diagnosed, both because of poor awareness by health workers and lack of implemented screening programs. An underrecognition of AATD diagnosis persists in spite of an effort to enhance clinicians’ awareness. From the clinical point of view the under-recognition might be explained by the facts that most of clinical phenotypes associated with AATD are not exclusive to this condition and that the abnormal genes have an incomplete penetrance (the relationship between genotype and clinical phenotype is not strong). The availability of alpha-1 antitrypsin replacement therapy for individuals with pulmonary emphysema associated with AATD encouraged the scientific community to establish and reinforce AATD screening. Screening for AATD has been recommended by the World Health Organization (WHO) in 1997. The American Thoracic Society (ATS) together with the European Respiratory Society (ERS) in 2003 advise population screening when three main conditions occur: 1) high prevalence of AATD (more than 1/1500), 2) high prevalence of smokers or of people exposed to toxic inhalants 3) availability of adequate genetic “counselling”. A population screening programme might be very innovative making use of new genetic techniques. An adequate screening program and an early diagnosis of AATD may permit to apply primary (i.e. smoking cessation for lung disease or alcohol abstention for liver disorders) or secondary (i.e. treatment of related lung diseases) prevention measures. At the moment there are evidences of neonatal screening, patient oriented detection (case-finding) and so called “targeted screening”. Recently, the Italian Association of “Alphas” coordinated a screening for AATD in the entire population of a small village in a high risk area.   

ONGOING RESEARCH AND DEVELOPMENT
Robert Stockley, University Hospital, Birmingham, U.K.

From the first recognition of alpha-1 antitrypsin deficiency in 1963 the research field became very active exploring the deficiency as a cause of all COPD. In the early 1980s augmentation therapy was introduced and with the understanding that this was “a cure” research activity waned. However in recent years a more inquisitive approach to the condition has emerged. Why do some AATD patients remain well? How does the lung disease present? How does it develop? How should patients be treated? What is the effect of chest infections? Can we prevent deterioration? Can we repair the damage? These and many other questions challenge us for the next few years. Of importance clinical trials of old or new treatments will emerge and be delivered through the extensive collaboration of researchers and the developments of the AIR and AOF registries. However it is critical that these are co-ordinated and not replicated merely to appease regulatory bodies. Close collaboration between medical registries, pharmaceutical companies and patient groups will be essential if we are to assess future therapies adequately.

3rd Alfa Europe Alliance Meeting
Saturday, May 10, 2008, Dorint Hotel Don Giovanni, Prague

Agenda
Dr. Thomas Köhnlein MD Hannover Medical School
Ongoing researches into alpha1-antirypsin deficiency
Dr. Pawel Kuca MD
National TB and Lung Diseases Research InstituteEpidemiology and detection program in Poland MU
Dr. Jan Chlumský, Ph.DDepartment of Pneumonology, Thomayer Teaching Hospital, Prague
Situation of alpha1 patients in the Czech Republic
Klaus SchäferTalecris Biotherapeutics GmbH in Frankfurt
Replacement therapy and Europe

Meeting of the delegates
Topics

1. Lung rehabilitation
2. Access to therapies
3. Access to insurance, mortgage, pension
4. Genetic discrimination within Europe                 

3rd ALFA EUROPE ALLIANCE MEETING SUMMARY

PRAGUE 9th – 10th MAY 2008  

All delegates gathered at the Hotel Don Giovanni on the afternoon of Friday 9th May..
We were welcomed to Prague by the Federation President, Larry Warren and Silke Horakava from the Czech Alpha Group who were our hosts for the Conference.  The AGM, initially consisted of voting and legal formalities, Larry Warren presented his President’s Report; in this he outlined events of the Conference in Rome last year.  

    * The alliance of the Alfa Europe Federation & the European Alpha 1 Foundation, has given the Federation a more stable footing and financial backing to run the Organisation and develop
    * The Federation membership is growing, with France and the Czech Republic joining this year and Poland, UK, Scotland and Portugal soon to be joining
    * It is important that The Federation is recognised by the EU Commission as a patient support partner, in order that Alpha Europe becomes recognised in the EU, this will eventually be for the benefit of all Alpha patients and their families
    * Larry Warren reported that the Federation already
          o Is a member of the Plasma and Protein Users group, which meets 4 times a year to look at the supply of produce etc
          o Has been accepted as a member of EURORDIS, the European Alliance for patients with rare diseases
          o Has applied for membership of EPPOSI, which is an alliance of patient groups, science and industry
          o Intends to build a working relationship with AIR, the Alpha 1 International Registry.
          o The above will ensure that the Federation is part of the planning for therapies, registries or any other matters that will affect Alpha sufferer
    * This year France has the EU Presidency and they have already given notice to the Federation that the French Government wishes to raise the profile of rare diseases ( of which Alpha 1 is one ) in the EU and look at how they are tackled and will hopefully draw up directives and recommendations to the Parliament and Commission, these will then be passed down to National Governments
    * In order to raise the awareness of Alpha 1 within the EU, delegates were asked to take back to their various groups and associations a request that Alpha patients right to their local MEPs telling them about Alpha 1 as an illness, how it affects them personally and their families lives and the problems they encounter with receiving treatments, therapies and reimbursements.

Nuccia Gatta, who has been Vice President and last year hosted the Rome Conference, explained how Italy along with Holland and Germany, have been doing the PAAIR (a collaboration between Patient Associations – PA- and the Alpha-1 International Registry – AIR), this will give the EU an example of how individuals involved in a rare disease can organise themselves to improve the diagnosis, care and treatment of a disease and the impact this has on patient care. We next went on to the Treasurers report, given by Juergen Schultz, explained that the Federation now had finance coming in from the Foundation, this apart from the 50euros membership fee paid by each member country, is, at present, the Federation’s main source of income. Conferences are funded by the Foundation, although the World Conference in Rome was funded by outside organisation. After discussion of the reports, the meeting moved on to electing officers

    * President – Larry Warren
    * Vice President – Sandrine Lefrancois  (nominated from the floor, Nuccia Gatta stood down)
    * Treasurer-  Juergen Schultz
    * Auditor – Elke Sadtler-Lison

By Orla Keane,
May 2008.