Dear Friends, Dear Families,
2022 is coming to an end, so I want to send you warmest wishes for a Happy Holiday Season!
And I want to sum up what has happened about reaching BCM cure in 2022, so please sit down because this is a long letter for you with several important pieces of information.
At BCM Families Foundation there are several projects that are moving forward and others that have stalled or need to get started.
CONCENTRATING PATIENTS’ DATA
For example, our BCM Patient Registry is a solid project, spanning the USA, Canada, the UK and all EU states, including Iceland, Norway, Switzerland and Liechtenstein. We have a very good Registry Manager, and we are followed by the Software House and the Data Protection Officer. The BCM Registry is under our full control, so we decide what to do with our data. I beg all of you to participate and help our BCM Registry grow, because this is where the information about our disease is finally collected together. It is of fundamental value to all of us as well to scientific research. The cost to maintain the Registry is $11,315 per year.
FUNDING RESEARCH TOWARD A CURE
The other project that has gone well and continues to bear fruit is our BCM mouse colonies, which have now moved with Dr. Wen Tao Deng from the University of Florida to West Virginia University. They will be part of a very important gene therapy testing project that we will be funding in the next few days. Many scientists helped us prepare this project, among them John G. Flannery, Ph.D. of the University of California Berkeley, Jay Neitz, Ph.D. of the University of Washington, William Hauswirth, Ph.D. Florida State University (retired), Wen Tao Deng of the West Virginia University. BCMFF is going to deliver $133,800 for this important project and we could need $50,000 more in 2023.
EARLIER, FASTER, MORE ACCURATE DIAGNOSIS
We continue to address not only patients’ data but also diagnosis. Many of us fail to be diagnosed, or have arrived at a misdiagnosis. This year I had contact with two families who, after the genetic test, saw their diagnosis changing from BCM to Achromatopsia. In some cases I was in contact with patients who had been diagnosed with “cone dystrophy” or “Leber Amaurosis” for years, before receiving a final diagnosis of BCM. There are even rare families (in ten years I have met 2 of them) in which patients carry the mutations of two different genetic diseases of the retina!
To reach your accurate diagnosis is a good reason why I’m here asking you to genetically confirm your diagnosis. Until the end of 2023, the University of Tübingen in Germany will receive an annual donation of $25,000 that will allow them to carry out the BCM DNA test free of charge for all families who request it.
So, hurry up, it won’t be like this forever.
To share my hope and my advocacy for needed improvement in diagnosing, I think that the time to reach diagnosis should be shortened – while avoiding erroneous and subsequent negative consequences. This should be achieved by better use and accessibility of currently effective and available diagnostic testing technologies, best practices and programs. New technologies and innovative approaches must be available to the diagnosis of BCM. Inequalities in access to diagnosis and ensuing care must end, through harmonization of standards and programs for the diagnosis of BCM and projects aimed at bringing even the most disadvantaged people to clinical and genetic diagnosis.
In light of this goal, stated above, BCMFF is very happy to have launched the Diagnostic BCM Videogame Project in collaboration with Erik Geslin, Ph.D. at Noroff University in Norway. We hope this diagnostic videogame will become a useful tool to identify BCM in the population of boys and men with BCM. Here too, new investments are needed to apply Artificial Intelligence to diagnostic tools and identifying more families. I’d like to thanks all boys who are helping the development of referral data for the Diagnostic Videogame and for any other AI Diagnostic tool.
We have investigated, “Why do so many BCM men and boys fail to know the name of their disease?” We believe it is due to the stability of this disease which is present from birth, and to the fact that people get used to it and compensate for the difficulties in their lives by developing adaptive behaviors. Furthermore, the disease is already present in the family so everyone makes comparisons with an uncle or a grandfather thinking they can have a similar life. Then, a majority of ophthalmologists do not indicate the right diagnosis name, together with eye examinations’ expense resulting that testing occurs only once, plus often the ophthalmologists doesn’t say, “I don’t know the name of your disease”, but instead tells the patient another generic name, for example “cone dystrophy” or “maculopathy”, to send him/you away with an answer, even if this is NOT an answer. Most of the time a BCM patient is told, “There is nothing you can do.” Medical expertise about BCM is rare, knowledge is scarce.
Many BCM patients have not even been sent to a low vision center to find contact lenses suitable to help their increasing myopia, filters for light sensitivity and magnification tools! Take advantage of all the advice that Dean Monthei will give you in this and in the other Newsletters about vision tools! Participate to the upcoming family meeting in Charlotte, NC where a low vision expert will be invited! And, help developing expertise in your area, as we did in 2022 with the Lissac low vision center of Rue de Rivoli in Paris, France.
So, this is a very significant challenge: we have to figure out how to find those other families, who don’t know the name “BCM”. This is why I ask that all of us participate in Rare Disease Day events on February 28 2023 and to spread information in your area about BCM. Together we can do it! Find more information here: https://www.blueconemonochromacy.org/rare-disease-day-2023/
MEETING OF FAMILIES
We had a beautiful meeting of European families in 2022, held in Venice in April, together with all the European achromatopsia organizations, with families who came from all the countries of Europe. It was a significant, very engaging moment with so many families with so much in common finally together!
We had many volunteers and ambassadors who worked and participated, not only at the meeting in Venice but also in the GivingTuesday fundraising campaigns. And we are very pleased to have an active new ambassador in Norway, Johan Caspar Wohlfahrt.
We tried to organize a beautiful meeting in Charlotte in October 2022, thanks to the superb work of Kay and Barbara, plus decisive support of Angie Honeycutt, work of our Ambassadors Ned Reade and John Cavitt with Jason Faulkner and Lindsey Egner, but due to Hurricane Ian we had to cancel the event. We are working to have the same meeting rescheduled at the end of April 2023, again in Charlotte, NC, and look forward to seeing many of you. The cost of the Charlotte 2023 Meeting will be $45,000.
WHAT WE HAVE TO FACE TOGETHER:
But I also want to let you know about other things that are wrong: First, in July 2022 Adverum Biotechnologies informed us that they did not have the funds to go ahead with the BCM trial and therefore put the intravitreal gene therapy development project on hold. Many biotech companies are in the same situation and many are selecting only some of the projects to carry on, waiting to find the funds for the others, often, as in our case, after years of involving those patient communities. I recognize that the current business model is wrong for the development of therapies for rare diseases, completely inadequate to advance the treatment, at the mercy of the financial markets. The support of patient organizations is essential for these therapies, it is important to involve patients with rare disease immediately: this is a request from the FDA and EMA, the drug oversight agencies. So, the patient organizations themselves, their efforts towards a cure, the hopes and the involvement of patients, all are at the mercy of the financial swings of the market.
It is not acceptable!
We have a rare disease and we want a drug development model that leaves no one behind, not the rarest, not the ultra-rarest –and the current market model of these biotech companies is not suitable. In fact, if they find money from investors, then, for a certain time they invest to develop gene therapies. If they don’t have money they stop or attempt sell to other biggest biotech companies. The therapy, if any will be reached, will then cure a few people a year. Resulting prices of rare therapies on the market are too high, thus inaccessible to patients. Therefore, why should our patient organizations support the development of expensive and, therefore, inaccessible drugs with our effort, commitment and resources?
The other thing that is wrong is the DNA test trend. When you finally reach an ophthalmologist expert in Inherited retinal Disease, she/he can consider to perform a fast and general genetic test to understand what kind of disease you have. We are verifying whether BCM DNA Test can be included in machines that perform the latest generation DNA tests, those that perform Next Generation Sequencing (NGS) and Whole Exome Sequencing (WES) tests. Sequencing the DNA here means that you can read the basis A, G, T and C of DNA and check whether there is a causative mutation, for example for BCM. Compared to conventional Sanger sequencing using capillary electrophoresis, the short read, massively parallel sequencing technique is a fundamentally different approach that revolutionised sequencing capabilities and launched the second-generation sequencing methods – or next-generation sequencing (NGS) – that provide orders of magnitude more data at much lower recurring cost.
Next-generation sequencing (NGS), also known as high-throughput sequencing, is the catch-all term used to describe a number of different modern sequencing technologies. These technologies allow for sequencing of DNA and RNA much more quickly and cheaply than the previously used Sanger sequencing, and as such revolutionised the study of genomics and molecular biology.
Exome sequencing, also known as whole exome sequencing (WES), is a genomic technique for sequencing all of the protein-coding regions of genes in a genome. It consists of two steps: the first step is to select only the subset of DNA that encodes proteins. These regions are known as exons —humans have about 180,000 exons, constituting about 1% of the human genome, or approximately 30 million base pair. The second step is to sequence the exonic DNA using any high-throughput DNA Sequencing technology.
You can consider that a person affected by an eye disease could have his/her DNA tested quickly on several causative mutations. We are currently investigating whether BCM could be included in these NGS and WES DNA tests.
If no, we must plan and finance a project to insert the test of BCM causative mutation in NGS and WES tools that will be the future of diagnosis for genetic diseases.
As we approach a New Year, my hope and vision for our future is that all of us will act as a community, in good and bad times, facing together difficulties and celebrating successes, putting efforts together to have a representative best-possible Patient Registry, to help others to reach an accurate diagnosis, to collect money for projects, to support scientific research, to prepare and participate in meetings together and events! I share my dream with you –together we can begin to see it happen!
I wish you all Happy Holidays and a Happy 2023.
Renata Sarno, Ph.D.
BCM Families Foundation