April 2009

Drop-in Support Group Meetings

A Breath of Fresh Air The second Canadian Respiratory Conference, called “A Breath of Fresh Air” will be held April 23 to 25, in Toronto at the Westin Harbour Castle Hotel. Alpha-1 Canada will be there to share information about Alpha-1 with healthcare professionals. While the meeting is designed for healthcare professionals the Ontario Lung Association is hosting a patient portion on the Saturday, April 25, 2009 from 2:00 p.m. to 4:00 p.m. Patient Presentations will include: Strategies for Coping With Indoor and Outdoor Air Pollution COPD Exercises and Strength Training Using Everyday Items in the Home  Protect Your Asthma From Home Invaders Parking will be reimbursed for the first 50 registrants! Pre-register by Friday April 17, 2009 by calling The Lung Association at 1-800-668-7682. The Ontario Lung Association will also reimburse, GO Train and subway fares. Refreshments will follow the workshops. Further information about the event and reimbursement is available here. The Canadian Organization for Rare Disorders (CORD) CORD is holding its Annual Conference in Ottawa on May 1st and 2nd, 2009. More information is available on their newly designed website. Check out their website and read more about the conference. Since Alpha-1 Canada is a member of CORD, any member of our community, whether you have Alpha-1 or not, can register for CORD’s conference at the deeply discounted “patient “rate.

In January 2009 we launched a new Tele-presence Drop-in Support Group. Any member of our community can call in using a toll free number and be part of the meeting.

Regularly scheduled meetings often do not fit with everyone's schedules and the number of time zones in Canada means there are few times during the day that work for everyone in a group. As a result, meetings are sometimes well attended and at other times, not so much so.

One of our groups suggested a regularly scheduled Drop-in for all Alphas and their caregivers, relieving the stress of trying to be available for meetings where the other members are counting on you to be there but you just can't fit it in.

We originally scheduled the meetings to be the 4th Thursday of every month so it would be easy to remember. Unfortunately when we try to find guest speakers, being tied to one day in particular does not allow us to be flexible with the speakers.

The meetings will continue to be monthly, but the exact dates may vary depending on speaker availability and other events that may be happening.

If you have registered for a Drop-in meeting in the past then you have all the information you need to attend any Drop-in meeting. If you plan to attend, please let us know by e-mailing Jim Mundy at jim.mundy@alpha1canada.ca.

If you have never attended or have misplaced the phone number contact Jim for the information you need to participate.

April's meeting will be on Wednesday April 29th and feature a talk by Dr. Denis Marier, MA, ND a doctor of naturopathic medicine.

About Dr. Marier Dr. Marier is a graduate of the Canadian College of Naturopathic Medicine and is a registered Doctor of Naturopathic Medicine with a practice focus in mind-body medicine, stress reduction, and naturopathic oncology. He has completed training in Mind/Body Medicine and Positive Psychology at Harvard University Medical School’s Institute of Mind/Body Medicine. Dr. Marier has also participated in naturopathic medical relief work following the Gujarat, India earthquake in January, 2001, and participated in the Nomad’s Clinic in rural Tibet in October 2004. He also volunteered in Sri Lanka following the devastating tsunami of December 26, 2004 and has volunteered in South Africa working with women and children affected by HIV/AIDS in 2006. He has also volunteered in Calcutta at Mother Teresa’s Home for the Dying Destitute and has an interest in naturopathic palliative care. Recently, Dr. Marier completed a master’s degree in Ecopsychology through Naropa University, bringing nature-based therapies and ecological considerations into his practice. Dr. Marier is committed to educating and empowering individuals on their wellness journey with the tools to reduce stress and enhance the body’s natural healing ability through individualized treatment. His compassion, humour and dedication inspire all those he works with.

The May meeting will be Thursday May 21st and feature Dr. Simon Ling who will speak about Alpha-1 liver disease in infants and children.

 

About Dr. Ling Dr. Ling has been Assistant Professor of Paediatrics at the Hospital for Sick Children, University of Toronto since 2003. He works in close cooperation with the liver transplant team at Sick Kids and is a member of the Alpha-1 Canada Medical Advisory Board. Dr. Ling is a Consultant in Paediatric Gastroenterology at the Royal Hospital for Sick Children, Glasgow, Scotland. Additionally, Dr. Ling collaborates in studies of the genetic determinants of liver disease due to cystic fibrosis and alpha-1 antitrypsin deficiency. Dr. Ling's complete bio can be viewed here.

In June, on Monday the 15th, our drop-in meeting will be our Annual General Meeting. Call in and meet our board of directors and find out what we’ve been up to over the past year.

As usual, the times are as follows:

4:00 pm Pacific Time	7:00 pm Eastern Time
5:00 pm Mountain Time	8:00 pm Atlantic Time
6:00 pm Central Time	8:30 pm Newfoundland Time

Changes to our website are coming

In December we reported that our website would soon be bilingual. Before we had it translated we thought it would be a good idea to review and update the entire English site first. That process is complete thanks to the efforts of our board, Medical Advisory Board and many volunteers.

Over the next couple of months we will be making all those changes to the English pages, so watch for a note at the top right of each page telling you when it was updated. If you don’t see that note on a page, it hasn’t been updated yet.

The French translation is almost complete and will soon be input. For technical reasons all the French pages will appear at the same time when the inputting is complete.

We’ve never done this before, so we can’t tell you exactly when we’ll be finished. Keep checking back to see the progress.

Pharmaceutical Industry News

Protein Origami

Normally, cells make proteins that are folded into various three-dimensional shapes and ferried to different areas of the body to do their work. Their work, ranges from fighting infections to helping orchestrate cell processes and are essential to life. But sometimes, because of genetic mutations or reasons scientists still don't fully understand, key proteins crumple into the wrong shape.

For example, everyone’s liver produces alpha-1 antitrypsin (AAT). The job of AAT is to protect the body from inflammation, especially in the lungs. In people with Alpha-1 their AAT is malformed or misfolded and cannot be released by their liver. Most commonly this leads to lung disease, but the build up of AAT in the liver can also lead to liver disease.

The simple misfolding of proteins can result in anything from Alpha-1 to cancer to mad cow disease. In some diseases, such as cystic fibrosis, misfolded proteins aren't transported to the part of the body where they are critically needed. In others, misfolded proteins clump into tangles known as polymers like the ones found in the brains of Alzheimer's patients. In people with Alpha-1 the AAT protein builds up in the liver and as a result isn’t transported to the lungs to protect them.

A growing number of Massachusetts companies have joined the search for drugs that could correct, clear away, or stabilize misfolded proteins and reverse the damage they cause.

The Boston Globe newspaper recently featured some of these companies. The following is information from the Globe about some of these companies.

"For a long time, people felt it was impossible; people had a preconceived notion that it was unlikely a small molecule could actually fix a broken protein…But it turns out that may not be the case," said Paul Negulescu, vice president of research at Vertex Pharmaceuticals Inc. Vertex is targeting errant, misfolded proteins in cystic fibrosis and Huntington's, and has just began a trial of the effectiveness of its cystic fibrosis drug.

"The whole protein-folding pathway has become an area of increased interest," Negulescu said. "It's kind of an exploding area."

Last year, Proteostasis Therapeutics Inc. raised $45 million for its work, which focuses on the entire cellular machinery that folds the proteins, transports them to the right part of the body, and degrades misfolded proteins.

Link Medicine Corp., a start-up that is focusing on ways to clear errant proteins like the ones that form toxic clumps in Alzheimer's and Parkinson's diseases, said in September that it had raised $40 million.

Satori Pharmaceuticals Inc., which raised $22 million in January, is searching for ways to block the formation of misfolded proteins in neurodegenerative diseases.

And FoldRx is expecting results this summer from a trial of a drug designed to stop a mutated protein from misfolding and accumulating in a rare genetic disease called Transthyretin Amyloidosis.

"Protein-folding therapeutics gets at the fact that there's a basic biological balance in the cell. Proteins have to fold into these complicated shapes, and getting folded when you're being jostled by your neighbours is not an easy thing to do," said Susan Lindquist , a cofounder of FoldRx and a member of the MIT-affiliated Whitehead Institute for Biomedical Research, in Cambridge. "All living organisms have the same problem, and in human beings it's an extreme problem; it plays a major role in the axis of health versus disease.

Lindquist has been studying heat-shock proteins, which play a critical role in helping proteins fold correctly under stress. She has found that some cancers exploit this stress response to help them survive, suggesting that the special proteins may provide clues for new cancer treatments.

A fungal spore heats up quickly when it enters a body - a stressful situation in which the heat-shock proteins perform a protective function, allowing proteins to fold correctly and function even under duress. That gives researchers a potential new drug target for fighting infections.

The diseases pharmaceutical companies are attacking by targeting misfolded proteins fall into two general classes: those that occur when proteins are not trafficked to the right area (Alpha-1 Lung disease), and those resulting when proteins clump together(Alpha-1 Liver disease).

One approach is to find a drug that binds to misfolded proteins, helping them fold and get to the correct part of the cell. That's the approach of Amicus Therapeutics, a New Jersey company working on creating drug chaperones that could be treatments for lysosomal storage diseases, in which waste accumulates in cells, causing a variety of problems - including deformity, neurological problems, even early death.

FoldRx is working on a therapy for transthyretin amyloidosis a rare genetic disease in which clumps of proteins form and build up in the heart and nerve tissues. Their drug, now in trials, stabilizes the proteins and prevents them from clumping.

Another approach is to tune up the processing and transporting of proteins in the body. That includes blocking production of errant proteins, or making sure misfolded proteins are broken down.

If you think of the cell as a hotel room, said Peter Lansbury, chief scientific officer of Link Medicine, "what you want to do is to keep that hotel room clean - reduce production of garbage and/or increase the housekeeping."

Chris Mirabelli, chairman of the board of Proteostasis, said his company is looking for ways to exploit "the natural biology, the natural network normally controlling protein function."

P. Michael Conn, professor of pharmacology at Oregon Health and Science University, suggested that one day diseases that involve misfolded proteins, such as Alpha-1, Alzheimer's and cataracts, could be treated by lifestyle medicines taken before symptoms even appear.

"By opening this new class of drugs," he said, "we're targeting a series of diseases, [and] have the ability to help people who could not have previously been helped."

GSK to share patents to aid disease fight

GlaxoSmithKline (GSK), a sponsor of Alpha-1 Canada and Europe's biggest pharmaceuticals group, announced recently that it will share as many as 800 patents it holds in an attempt to find cures for rare diseases.

The announcement, which came in the company's annual corporate responsibility report, will allow others seeking treatments for some rare diseases, many of which are prevalent in some of the poorest parts of the world, to use GSK's intellectual property. The company also said that it would cut the price of 110 patented medicines, including treatments for diseases such as malaria.

Kamada Completes Last Patient Visit in Phase II Bronchiectasis Study with its Inhaled AAT

Kamada, a bio-pharmaceutical company engaged in the development, manufacturing and marketing of specialty life-saving therapeutics, announced recently that it has completed the last patient visit in a Phase II bronchiectasis study with its Inhaled Alpha-1 Antitrypsin (AAT), delivered via an optimized Investigational eFlow Nebulizer System (PARI Pharma GmbH). Preliminary results indicate that the product continues to demonstrate a good safety profile; final analysis of airway inflammation and secondary endpoints is expected to be available by mid-year.

David Tsur, Kamada's CEO expressed enthusiasm at the advancement of Inhaled AAT for the treatment of bronchiectasis. “This is another milestone for Kamada in the development of Inhaled AAT. Bronchiectasis affects approximately 600,000 people world-wide and we believe our novel approach, which could impact the underlying inflammatory processes, may considerably improve the quality of life of these patients. We look forward to receiving the final data from this study in the coming months," said Mr. Tsur.

According to Pnina Strauss, Kamada's Clinical Trials and IP Manager, "This is the third Phase II clinical trial we have conducted with Inhaled AAT and we continue to observe a very promising safety profile.”

In Need of a Diagnosis

According to an article published in the Journal of the American Medical Association, doctors misdiagnose fatal illnesses in 20 out of 100 cases in the United States. Surprisingly, only 6 percent of deaths in the United States are examined through an autopsy, according to CBS news.

Some commonly misdiagnosed diseases include the following:

• Cancer: Misdiagnosis of cancer usually happens because proper screening guidelines were not followed or because lab results were misinterpreted. Breast, pancreatic and colorectal are commonly misdiagnosed cancers.
• Heart attacks: Heart attacks often do not involve obvious symptoms. Sometimes the patient experiences nausea, mild shortness of breath, mild pain in the chest or a feeling as if their chest is full.
• Aortic dissection: This condition occurs when the aorta, or the heart's major artery, is torn. Patients can feel when this happen, but it is often misdiagnosed as a condition with similar symptoms, such as a myocardial infarction or pulmonary embolism. Actor John Ritter died of this condition. His surviving wife settled a wrongful death suit against a hospital in California who she says misdiagnosed him at least twice.
• Clogged arteries: Doctors may misattribute shortness of breath, a symptom of coronary artery disease, to obesity or being overweight.

Sometimes a diagnosis doesn't occur because the condition a patient has is so rare. In the United States, a rare disease is categorized as one that afflicts less than 200,000 people. There are more than 7,000 diseases classified as this. Canada has no official definition of a rare disease. Primary care physicians who have a patient with a complex, undiagnosed disorder can refer them to other specialists.

Last year, the National Institutes of Health launched the Undiagnosed Disease Program to study some of the most difficult to diagnose cases. The main goals of the research project are to provide patients suffering from mysterious conditions with answers and also to advance the medical community's knowledge about diseases. The 50 to 100 patients accepted into the NIH clinical study will be evaluated at the NIH Clinical Center in Bethesda, Md. by dozens of NIH physicians.

Researchers identify gene variant associated with COPD

Researchers from Boston University School of Medicine (BUSM) have, for the first time, identified a gene variant on chromosome 4 that may be a potential risk factor for chronic obstructive pulmonary disease (COPD). Their findings were published in PLoS Genetics on March 20th.

COPD is the fourth leading cause of death in Canada and the United States and one of the most prevalent disabling diseases of adults. According to the researchers, cigarette smoking is the primary risk factor for impaired lung function, yet only 20 percent of smokers develop COPD. This observation, along with family studies of lung function and COPD, suggests that other genetic factors in addition to Alpha-1 influence susceptibility to cigarette smoke.

Researchers have for a long time believed that there were other genetic factors influencing the progress of Alpha-1 since some people with Alpha-1 do not become sick.

The researchers performed a genome-wide association study on 7,691 Framingham Heart Study participants to identify a relationship between common genetic variants and measures of lung function. The identified variants on chromosome 4 were then examined and confirmed in an independent set of 835 Family Heart Study participants.

“Several interesting genes are present in the region that we identified, including a gene (HHIP) interacting with a biological pathway involved in lung development, but it is not yet clear which gene in the region explains the association,” said lead author Jemma Wilk, D.Sc., an assistant professor of neurology at BUSM. “Our results identified a region of chromosome 4 that warrants further study to understand the genetic effects influencing lung function,” she added.

The Framingham Heart Study, which has been administered by BUSM faculty in cooperation with National Heart, Lung and Blood Institute since 1971, was initiated in 1948 to identify factors contributing to cardiovascular disease, principally heart attack and stroke.

This research was conducted in part using data and resources from the Framingham Heart Study of the National Heart, Lung, and Blood Institute of the National Institutes of Health and Boston University School of Medicine.