President’s Report – 2023

As I look back on the activities and accomplishments of last year, I conclude that 2023 was a productive year for the SDHB Coalition and we continue to make progress in a number of different areas.  We successfully held our annual “in person” gala on April 27, 2023, in New Jersey.  While it is clear that there remain many challenges to organizations such as ours in a post Covid environment, the event was by all accounts a success despite lower attendance and contribution levels when compared to pre-covid years.  Our focus in 2023 continues to be on sponsoring research and increasing awareness.  The challenges referenced above have resulted in reduced levels of funding but despite this, by leveraging our resources, we were able to have our best year yet in terms of sponsoring research.  We have also worked hard to increase awareness through our social media efforts and by attending select events to further our efforts in this regard. 

I would like to thank our board, volunteers, individual contributors, corporations who continue to support us in this regard.

During 2023, In addition to ongoing work at other institutions, we have supported the following research activities which includes four new grants at the University of Arizona, Stanford University, University of Florida and Linkoping University in Sweden. Details to follow:

At the University of Arizona, we continue to support the research scientist-surgical oncologist team who are studying SDHB signaling mechanisms that drive pheochromocytoma and paraganglioma. They have produced very promising results so far and we can highlight a few of them. One of their objectives is to advance a biomarker detection system and they have completed preclinical studies showing the biomarker detection reagents at the immunohistological level. They are also trying to develop a drug screen to identify novel compounds that target Cdk5/p25 as inhibitors, disrupters of Cdk5/p25 protein-protein interactions, or binding compounds to be developed into targeted protein drug degradation (PROTAC) reagents.  This grant focuses on anti CDK-5 interventions and possible human therapies, and we are very excited to be sponsoring some of this work.

In 2019, we agreed to support a project at the University of Florida that will perform large scale metabolic analysis on an outstanding set of 50 novel PCC/PGL frozen tumor samples to interrogate the consequences of alterations in the SDHB cascade and identify perturbed metabolic pathways. This will enable scientists to better understand the metabolism in the PCC/PGL cells. In 2020 and 2021 the work continued; however, it was decided that they needed to expand the number of fresh frozen samples to 100 which they did. A more comprehensive metabolomics is currently being performed to assess the extent to which the polyamine pathway is upregulated in SDHB mutated tumors. Potentially targeting the polyamine pathway is important because cells are not able to survive without this pathway. This study was delayed due to Covid and continued during 2022 to initiate experiments to test polyamine inhibitors both in vitro and in vivo. This continued in 2023.

As mentioned above, we are also sponsoring a grant at Stanford University which got underway in 2023. We are very excited about this work which will focus on developing an improved SDHB tumor model. In addition, efforts are underway to identify unknown SDHB-deficient pheo/para tumorigenic genes in vivo. We are looking forward to providing more information on this effort in the future. If successful, new findings could shed new mechanistic insights and provide an excellent pre-clinical model for therapeutic investigation.

Finally, we funded a new grant at the University of Linkoping in Sweden to identify new drugs for the treatment of malignant pheochromocytomas and paragangliomas. This is a very important project since we have so few therapeutic options at the moment.

As it relates to other ongoing activities, at the University of Columbia, we continue to support the establishment of a PC/PG registry, comparing gene expression profiles following exposure to epigenetic agents with controls, and evaluating the cytotoxicity of agents that alter gene expression. Importantly, good progress is being made especially with the registry which takes many years when creating a valid patient database in a rare disease where there are so few patients, and this work is ongoing.

In 2019, we approved new funding for a project at the University of Melbourne in Australia with an objective of identifying changes in the genes that regulate cell behavior to better understand what initiates the process of spreading to distant sites and to identify precision treatments for patients. This study continued in 2022 and we are working closely with the architects on their findings.

Regarding our focus to increase awareness and more specifically communications, we continue our social media efforts with our Facebook, Instagram and LinkedIn platforms and are adding content and infographics that can be used to update the social media pages. We have also started to receive small individual donations due to our Facebook and Instagram outreach. We continue to make available  “YouTube” videos that describe the disease in detail for both healthcare professionals and patients and have posted them on our website.  We also have received positive feedback on our newsletter, which is in the process of being updated and will be published in 2024. 

Our objectives for 2023 were as follows: The following represent a few comments on what we accomplished against our 2023 objectives.

1. To continue to spread the word about the SDHB PheoPara Coalition and to fulfill our mission. We believe we met this objective by holding our in-person Gala on April 27^th, 2023, and through our social media efforts previously mentioned in this report.
2. As part of our succession planning initiative, our plan was to add additional board members who could serve in the future and provide ongoing continuity for the Coalition. We added two new younger board members in 2022, namely, Antony Rothwell and Adam Hooper. We also reviewed our committees and consolidated some and modified their membership to streamline our activities and will continue to identify more volunteers who would like to serve going forward. Accordingly, we believe we met this objective for 2023.
3. To support at least 1 or 2 good and new SDHB scientific projects which will lead to a better understanding of the role of the SDHB germline mutation in this disease and ultimately an effective treatment. We accomplished this objective as mentioned above.
4. We finalized a marketing plan and began implementation with the objective of increasing brand awareness of the SDHB Pheo Para Coalition and the SDHB germline mutation as well as its role and impact in this orphan disease. We also wanted to raise money from different sources to support treatments that can help treat this disease. This has been difficult since Covid, but we made progress in 2023 when compared to 2022.
5. Continue to look at social media opportunities which will allow us to spread the word to different audiences.

Our objectives for 2024 are consistent with those in 2023 and are essentially the same and we remain confident that we can accomplish same.

Thank you for your interest and continued support of the SDHB Coalition.

Tim Rothwell,
President