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“The Independent Charities Seal of Excellence is awarded to the members of Independent Charities of America and Local Independent Charities of America that have, upon rigorous independent review, been able to certify, document, and demonstrate on an annual basis that they meet the highest standards of public accountability, program effectiveness, and cost effectiveness. These standards include those required by the US Government for inclusion in the Combined Federal Campaign, probably the most exclusive fund drive in the world. Of the 1,000,000 charities operating in the United States today, it is estimated that fewer than 50,000, or 5 percent, meet or exceed these standards, and, of those, fewer than 2,000 have been awarded this Seal.”
Remember: 95-98% of your donation goes to medical research.
Gaucher disease is an example of a “Mendelian” disorder, where defects in a single gene are the primary cause of the disease. Many common human diseases, such as hypertension, diabetes and arthrosclerosis, result from interactions between multiple genes and environmental factors such as diet, infections or exposure to toxins. In order to understand the changes in cellular mechanisms that result in these complex, or “multigenic’, diseases, researchers can gain information from rare, single gene disorders that share symptoms with more common, complex diseases.
Unfortunately, it is a familiar story to those of us who study rare genetic disorders – lack of funding. Neuronopathic Gaucher disease is also a victim of this dire situation. For those few who are fortunate enough to have the resources to study this disease, it is often a lonely and secluded existence. We are scattered in hospitals and laboratories around the world doing the best that we can with finite resources and limited budgets. When faced with these hurdles, communication between us is critical in terms of sharing ideas, data, expertise, establishing collaborations and avoiding wasteful repetition. Although the world is becoming smaller in terms of our ability to communicate, nothing quite equals the experience of a good face-to-face discussion.
From around the world, experts on the brain meet in Atlanta Georgia
It was for exactly this reason that I was so pleased to be invited to attend a meeting organized by the Children’s Gaucher Research Fund in Atlanta. Under the Chairmanship of Professors Tony Futerman (Weizmann Institute, Israel) and Raphael Schiffmann (Baylor Institute, USA), experts in the fields of Neuronopathic Gaucher disease and other closely related neurological diseases were asked to attend. Furthermore, representatives from industry were also present. The format was unconventional in that this was not typical of a conference. Rather, it had the feel of an informal lab meeting with all present sitting around a single table. It reminded me of the old Arthurian Legends in which all Knights of the realm sat as equals with the King within Camelot. In a similar fashion, everyone from Professors down to PhD students were free to speak, criticize, encourage and present their views and data. The discussions were open, frank and to the point. I found it both refreshing and enlightening.
A broad variety of subjects were raised by attendees including: gene therapy (Dr Ahad Rahim, University College London, UK), other alternative therapies (Dr Seng Cheng, Genzyme, USA), disease pathophysiology in mouse models (Dr Einat Vitner and Ms Tamar Farfel-Becker, Weizmann Institute, Israel), biochemistry and cell biology (Dr Greg Grabowski), clinical perspectives (Dr Raphael Schiffmann, Baylor Institute, USA and Dr Ashok Vellodi, Great Ormond Street Hospital, UK), the link between genotype and phenotype (Dr Andres Klein, Weizmann Institute, Israel).
Three distinct presentations were also given on the association between Gaucher disease and Parkinson’s disease (Dr Ellen Sidransky, NIH, USA, Dr John Hardy, University College London, UK and Dr Dimitri Krainc, Harvard Medical School, USA). The link between these diseases is attracting significant attention from research groups around the world. Research into Parkinson’s disease is significantly better funded than Gaucher disease. It benefits from having a higher profile due to its more significant impact on global health in an ageing population. By association alone, this is likely to raise awareness of Gaucher disease.
Another useful feature of the meeting was the presence of experts in diseases similar to neuronopathic Gaucher disease. These included: Professor Alessandra d’Azzo (St. Jude Children’s Hospital, USA), Professor Volkmar Gieselmann (University of Bonn, Germany), Professor Marc Patterson (Mayo Clinic, USA), Dr Konstantin Dobrenis (Albert Einstein College of Medicine, USA), Professor Daniel Ory (Washington University School of Medicine, USA), Dr Morris Benveniste (Morehouse School of Medicine, USA) and Dr Emyr Lloyd-Evans (Cardiff University, UK). They provided invaluable input and highlighted both similarities and differences between the neurological diseases they work on and Gaucher disease. It is often very easy to become very ‘Gaucher-centric’ and insular so objective points-of-view are welcome and we can draw from each other’s pools of knowledge.
This was an excellent meeting and I came back to the UK more informed, with new ideas and contacts that will hopefully form fruitful collaborations. What was clear to me is that significant advancements are being made in our understanding of this terrible disease. This, in turn, will help scientists, like myself, design and target novel therapies that will have a tangible impact on the lives of patients. The presence of representatives from industry is vital in making such a therapy scalable and realistic from a production and economic point of view. The clinicians amongst us have the vital role of translating any therapeutic advancement from the bench to the clinic. Therefore, all the players required in this sequence of events were present in Atlanta and this does not happen often.
I sincerely hope that the CGRF will organize future meetings because this one was very useful.
Dr. Ahad A. Rahim
Gene Transfer Technology Group
Institute for Women’s Health
University College London
London, UK
As many of you know I have been working on neuronopathic Gaucher Disease for over a decade in my lab at the Weizmann Institute in Israel. We have made great progress creating the “building blocks” of understanding.
This progress has happened because of the support received by the CGRF – or more personally – because of your generous support. However, one of the frustrating aspects with research in this area is the small number of people who have been working on this disease. The meeting that was held in Atlanta brought together in an informal setting 25 brain experts from around the world, some of whom had previously worked on Gaucher Disease and a number who were totally new to the field but work on various aspects of brain diseases. Getting this group together was of enormous importance, as it is sure to foster new collaborations and new ways of thinking about the disease.
As far back as our 2006 Brain conference two things became clear:
1) That research being conducted on various brain diseases were starting to find similarities between and among different neurological diseases.
2) Parkinson’s research was beginning to connect the dots to a possible GBA link.
We purposefully invited medical researchers from the the Parkinson’s field of research as well as researchers pursuing other brain diseases. We set aside ample time for presentations – and to say the least the discussion and debate was lively. At the 2006 conference Dr. Ellen Sidransky from the National Institutes of Health presented her research, and since that time she and others have continued their quest to determine if indeed there is a link that deserves further exploration. Below is a article published last fall in the LA Times summarizing some of the most recent research findings, and substantiating the direction we took with the 2006 agenda.
Gaucher disease linked to Parkinson’s
Los Angeles Times, October 21, 2009 | 5:04 pm
People who carry the gene for a rare genetic problem known as Gaucher disease have at least five times the normal risk of developing Parkinson’s disease, researchers reported today in the New England Journal of Medicine. Some clinicians had noticed an apparent link between the two conditions in the past, but a new international study of nearly 5,700 people is the first to show the magnitude of the risk. The finding suggests that the gene is one cause of the disease, but indicates that other factors must be operating as well because not all patients who have Gaucher also develop Parkinson’s.
Gaucher disease, which afflicts an estimated 5,400 Americans, is caused by defects in the gene known as GBA, which serves as the blueprint for the production of an enzyme known as glucocerebrosidase. The enzyme breaks down a fatty substance called glucocerebroside which, when not disposed of, can harm the spleen, liver, lungs, bone marrow and, in some cases, the brain. People with two defective genes suffer from the disease, which comes in three distinct types. Lifespan may range from as little as 2 years to as many as 40 or 50.
People with only one defective gene do not suffer from symptoms and are said to be carriers. About one in 100 Americans carries the gene, but among certain groups, like Ashkenazi Jews, the incidence rises to one in 15. It was previously thought that the gene was harmless in such people, but the new results show that is not the case.
Dr. Ellen Sidransky of the National Human Genome Research Institute had been intrigued by an observed link between Gaucher and Parkinson’s. To explore it, she organized a consortium of 64 researchers at 16 institutions worldwide–virtually every Gaucher researcher in the world. They studied two common GBA variants in 5,691 people with Parkinson’s disease, including 780 Ashkenazi Jews, and compared them to 4,898 disease-free individuals, including 387 Ashkenazi Jews.
They found that 3.2% of the Parkinson’s patients had at least one of the common variants, compared with only 0.6% of the healthy people, a five-fold increase. Among the Jews, 15.3% of those with Parkinson’s carried the gene, compared with 3.4% of healthy Jews.
Five of the research centers sequenced the entire GBA gene in 1,642 non-Ashkenazi Parkinson’s patients and 609 health non-Ashenazis, looking for other mutations. They found mutant genes in 7% of the patients, indicating that their risk of developing Parkinson’s was 10 times normal.
The finding does not offer any new ideas about how to treat Parkinson’s disease. Indeed, researchers are currently at a loss to explain the mechanism by which the defective gene increases the risk of Parkinsonism, which affects an estimated 3 million to 4 million Americans. But they hope that exploring the link will provide new information about how the disease develops and progresses.
