Our current understanding of ALS comes almost exclusively from studying a very small proportion of the world. Some of the largest leaps forward in our learnings to date have come from studying the genetics of individuals with ALS, yet most of the world’s genetically diverse populations are nowhere to be found in the databases being used. Unfortunately, many underrepresented global populations lack the infrastructure to support quality care, let alone research. Starting research in many of these regions is also complex. Usually, it requires a local doctor or advocate to champion building a foundation within the area that addresses the value of research in the appropriate way for the regional culture.
History shows that critical, timely investments in the work of key clinical leaders in areas on the cusp of starting research on ALS can go a very long way toward stimulating larger follow-up investments that pave the way for exponential growth and impact. This initial work often requires collaboration between experts from well-supported regions of the world and local clinician experts to develop the appropriate mechanisms within the local systems and culture.
South America and Africa are massive, heavily populated continents where even using the term underrepresented in ALS research is an understatement. However, the work of some key individuals over the past few years has helped position both continents toward a path of contribution to our global understanding of ALS that could be significant.
One of these individuals is Professor Mónica Povedano of Hospital Universitari de Bellvitge in Barcelona, Spain, who, in collaboration with Professor Orla Hardiman of Trinity College Dublin, has been working with colleagues in Colombia and Ethiopia to make inroads on building clinical and research infrastructure in South America and Northern Africa.
To support this work, an ALS Canada Acceleration Grant was awarded to Professor Povedano to collaborate with Dr. Martha Peña of the Roosevelt Institute in Bogotá, Colombia and Dr. Dereje Melka at Addis Ababa University in Ethiopia to enhance their blossoming research capacities by doing the first ever comparative study in ALS across these diverse ethnic backgrounds alongside data from European individuals. The study will first focus on differences in the distribution and characteristics between the groups but also use validated measures of disease and genetics for these comparisons. In South America, some of the foundational work was started by Prof. Hardiman in collaboration with a Latin-American Epidemiologic Network for ALS (LAENALS). Prof. Povedano will work closely with LAENALS as well.
Update
In the first several months of their ALS Canada Acceleration Grant funding, things have evolved in South America. In September 2023, Dr. Peña, Prof. Povedano, and Prof. Hardiman, held the inaugural meeting of a new South American ALS clinician network called ELATAM. In Africa, a network of clinics is also developing through Prof. Jeannine Heckmann in Cape Town, South Africa. Providing seed funding to support Ethiopian research can hopefully add to the momentum on the continent.
Dr. David Taylor, Vice-President of Research and Strategic Partnerships at ALS Canada, feels the timing is perfect for this Acceleration Grant. “Incorporating the contributions of underrepresented areas will be critical to our understanding and ability to treat ALS, and this can’t happen without initial investments to build the foundation. It’s important that we grab this present opportunity of having strong leaders in these areas and support them to expand and evolve research capacity so that the world can benefit as soon as possible.”
Contributing globally helps Canadians
Beyond learning from disease statistics, genetics, and environmental impacts in these regions, developing the infrastructure to support clinical trials is a win-win scenario for people affected by ALS in these areas and for affected individuals around the world (including Canada). Running trials in underrepresented regions will bring potentially beneficial experimental therapeutic access to these countries and accelerate opportunities to discover treatments available to Canadians if they work.
One current example of this mutual benefit lies in treatments for individuals with SOD1 ALS, a form caused by a variant in the superoxide dismutase 1 gene. An effective treatment called tofersen is approved as Qalsody in the United States but is also available in many countries through expanded access programs provided by Biogen. Despite the benefit of tofersen, multiple companies are trying to improve on its success by targeting SOD1 ALS with potentially more robust and less burdensome or invasive delivery. For the world to learn if these new options can provide greater value, studies would need to recruit individuals and doing so in areas where tofersen is available will be difficult. However, in African and South American clinics where there is a significant number of people with SOD1 ALS, these exciting new experimental treatments could be accessed by local individuals while the rest of the world can learn from their involvement in these studies.
The progressive nature of ALS necessitates urgency in our scientific attempts to understand the disease, but the complexity of the disease suggests longer-term strategies that could yield a significant impact, which are also important complementary pieces. We need to tackle ALS from all angles, and the learnings from regions of the world that we have yet to begin to look at will undoubtedly provide crucial information toward our vision of a world free of ALS. Through this Acceleration Grant, we are strategically investing in work that will eventually bring entire continents into the global effort, ultimately speeding up impact back to future Canadians diagnosed with the disease.