ALS Research on Genetic Testing and Counseling Provides Evidence-Based Consensus Guidelines for Clinicians


Jennifer Roggenbuck, MS, LGC, an associate professor of neurology and internal medicine at The Ohio State University Wexner Medical Center, discussed her presentation on evidence-based consensus guidelines for genetic testing and counseling from the 2022 NEALS Consortium.

associate professor, department of neurology and internal medicine, The Ohio State University Wexner Medical Center

Jennifer Roggenbuck, MS, LGC

Recently, gene discoveries and gene therapy trials have increased the interest in genetic testing for people with amyotrophic lateral sclerosis (ALS). Although, clinical genetic testing for people with ALS is not considered currently standard of care and not all the patients that want access to testing are able to get it.

At the 2022 Annual Northeast Amyotrophic Lateral Sclerosis (NEALS) Consortium Meeting, held November 1-3, in Clearwater Beach, Florida, Jennifer Roggenbuck, MS, LGC, and colleagues presented a presentation on findings from a rapid review that showed that the ALS Association-sponsored research showcases specific recommendations for clinicians on genetic testing and outlines information for patients to know before and after testing.1

The review was conducted in accordance with Meta-Analyses (PRISMA-P) 2015 guidelines and the Preferred Reporting Items for Systematic Reviews. Eligible studies were based on the amount of evidence on clinical ALS testing and counseling guidelines. The recommendations were assessed on their strength or evidence using 2 combined systems: the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) System and the Evaluation of Genomic Applications in Practice and Prevention (EGAPP).

The search yielded articles (relevant, n = 9541; duplicates, n = 1794) from the online databases of Medline, EMBASE, and CINAHL from inception to March 2021. Of those, 939 articles were selected for the full-text review after the application of the inclusion and exclusion criteria. Then, 454 articles were selected for the development of recommendations (n = 45) in a draft guideline after the full-text article review.

Roggenbuck, associate professor, department of neurology and internal medicine, The Ohio State University Wexner Medical Center, sat down with NeurologyLive® and spoke about her abstract presented at the 2022 NEALS Consortium. She discussed an overview of the guidelines along with the short-term and long-term goals of the guidelines.

NeurologyLive®: Can you provide an overview of these newly developed guidelines, and were there any certain aspects or themes you and your colleagues keyed in on?

Jennifer Roggenbuck, MS, LGC: We are now able to find a genetic cause of ALS in greater than 10% of persons who have ALS. We know that persons with ALS are interested in genetic testing to understand the cause of their condition, to know if their relatives are at risk, and also to know if they might be a candidate for clinical trials of gene targeted therapies now being rapidly developed. However, most persons with ALS are not offered genetic testing.

Along with my neurologist colleagues, Dr. Stephen Kolb, and Dr. Matthew Harms, I wrote a proposal to develop evidence-based guidelines for the practice of genetic testing in ALS, and we were funded by the ALS Association. We reviewed the medical literature, developed our specific recommendations, and recruited an expert panel to refine and approve them. Our core recommendation is that genetic testing and counseling be offered to every person with ALS. Providing genetic counseling is critical, so that patients can make an informed decision about testing and understand the implications of the test result. The final portion of the guidelines provides specific direction to testing laboratories that conduct this testing and deals with methods and reporting. We looked at all the evidence to really provide a comprehensive set of guidelines that are designed to improve and standardize all aspects of the genetic testing process in ALS.

Currently, which areas of genetic testing for patients with ALS do we excel in and struggle with? Has there been any other consensus among clinicians on how to approach genetic testing?

We've studied clinician testing practices and there is no consensus, and this was one of the core issues we sought to address. Access to genetic testing shouldn't depend on which clinic you go to or where you live; we want all patients to have access to this service and be empowered with knowledge about their genetic status.

We excel in terms of our technology; we can now sequence DNA at a relatively low cost and that's been a major change over the past 10 to 15 years. As mentioned, we have not excelled in consistently offering testing to all patients with ALS. In addition, we've struggled in providing patients with comprehensive education before and after testing. So, we've observed that some patients who are getting testing don't necessarily understand the implications of the results.

Do you envision these guidelines could open up access and expand genetic testing for potentially more governmental recognition?

We do hope that the publication of the ALS genetic testing guidelines will support broad access to genetic testing. We hope that neurologists, whether they're in the community, or academic neurologists, and any provider caring for persons with ALS, will have a have a roadmap to guide the offer of genetic testing, as well as patient education. If that's not something that particular provider is comfortable with, then at that point, a referral might be needed to a tertiary ALS center, or a genetic counselor to help that particular patient access testing. That's the first step. Next, we do hope that the guidelines will drive payers and governmental agencies to recognize the importance of genetic testing as a key component of ALS management. The very first new drug application for a gene targeted therapy for ALS is currently under FDA review. We're in a new era of clinical actionability of genetic testing in many areas of neurology.

Are there any short- or long-term goals with these guidelines?

The primary goal is to facilitate universal patient access to genetic testing and genetic counseling. We hope to standardize the practice of genetic testing so that it's the same whether you are a person with ALS in New York City seeing a multidisciplinary ALS clinic team, or if you are a person with ALS in rural Nebraska. The urban vs rural divide is one of many health care disparities that impacts ALS management. Our long-term goal is broad recognition of genetic testing and counseling as a key and required aspect of ALS management. Genetic diagnosis and genetic counseling can impact families for generations, allowing presymptomatic testing, preimplantation genetic diagnosis, and very soon, approved therapies for affected persons. I believe the treatment of healthy gene carriers is just around the corner.

Transcript edited for clarity. Click here for more coverage of NEALS 2022.

1. Roggenbuck J, Eubank B, Wright J, Kolb J. S, and Harms B. M. Development of Evidence-based Consensus Guidelines for ALS Genetic Counseling and Testing. Presented at: 2022 Annual NEALS Meeting; November 1-3; Clearwater Beach, FL. Abstract 117

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