Director's Blog
A Discussion with Genetic Scientists Advancing Preclinical Genome-Guided Therapeutics in the UAB NF Research Program
The UAB NF Research Program is dedicated to the discovery and development of new, life-changing therapies for people with all forms of NF. To advance this mission, UAB maintains a robust and internationally recognized research program that includes a range of preclinical research and clinical trials for all forms of NF. The primary focus of our program is the development of genome-guided therapeutics with the goal of restoring function to the mutated NF1 gene or gene product. We have been pioneers in this effort for NF1 and have developed resources to enable this research through many funding sources, including the Gilbert Family Foundation, a private foundation established for the purpose of developing effective therapies for NF1.
This month’s blog features insight from two genetic scientists collaborating on preclinical research projects focused on genome-guided therapeutics. Deeann Wallis, Ph.D., UAB Associate Professor of Genetics, and Robert Kesterson, Ph.D., Professor of Cancer Precision Medicine and Director of Genetically Engineered Models facility at the Pennington Biomedical Research Center at Louisiana State University (and formerly Professor of Genetics, UAB), give an overview of promising preclinical research initiatives and discuss the strengths of the UAB NF Program in accelerating the development of genome-guided therapeutics with the potential to transform the treatment landscape for NF.
Read moreOverview of the UAB NF Clinical Trials Consortium: A Discussion with Members of the Operations Center Administrative Team
The identification of genes associated with NF1, NF2, and some forms of schwannomatosis has opened new opportunities for testing medications that may be effective in preventing or treating complications of neurofibromatosis. As an international leader in advancing neurofibromatosis research, UAB serves as the coordinating center for the NF Clinical Trials Consortium, an innovative research initiative committed to transforming the NF therapeutic landscape.
This collaborative group of 15 primary and 10 affiliate clinical centers across the country and in Australia is dedicated to conducting clinical trials of the most promising drug therapies for all forms of neurofibromatosis. Established in 2006, the Consortium is funded by the Department of Defense (DoD) through the Neurofibromatosis Research Program (NFRP), one of the Congressionally Directed Medical Research Programs. Following a recent successful renewal application, the Consortium is now funded by the DoD for the next 10 years.
The Consortium partners with well-established NF Centers that pool expertise and resources to accelerate the pace of research by providing opportunities for patients to participate in clinical trials at sites around the country and in Australia. I serve as the Principal Investigator of the Consortium and lead the Operations Center based at UAB; Children’s of Alabama Division Director of Pediatric Hematology and Oncology Girish Dhall, MD, serves as Deputy Director of the Operations Center.
This month’s blog features insight from members the NF Clinical Trials Consortium Operations Center administrative team, which is based at UAB, including: Program Director Karen Cole-Plourde, BS; Clinical Research Nurse Manager Lynn Merritt, RN; and Research Compliance Manager Juliette Southworth, BS, CCRP. These dedicated professionals explain their roles and share observations about the impact of the NF Clinical Trials Consortium in accelerating the pace of NF research and providing meaningful opportunities for patients across the country and internationally to participate in clinical trials of promising new therapies.
Read moreThe Role of the UAB Medical Genomics Laboratory in NF Patient Care and Research
The UAB Medical Genomics Laboratory serves an integral role in supporting patient care and advancing neurofibromatosis research. Viewed in the medical and scientific communities as the gold standard for NF genetic testing, the laboratory offers clinical genetic testing for all forms of neurofibromatosis, including NF1, NF2, Schwannomatosis, as well as Legius syndrome and other Rasopathies. Based on more than 15 years of experience, the Medical Genomics Laboratory has identified mutations in more than 8,000 unrelated patients and has identified more than 3,000 NF1 mutations, representing the world’s largest database repository of NF mutations. This month’s blog features insights from the Director of the UAB Medical Genomics Laboratory Yulong Fu, PhD, FACMG, and Laboratory Genetic Counselor Bryce Brown, MS, LGC. Dr. Fu and Mrs. Brown discuss how the laboratory’s unique testing capabilities, advanced technologies, and distinctive expertise support patients, physicians, and research scientists by providing information about NF variants that may be otherwise unavailable.
Read morePhysicians Share Insight about Providing Care to Patients in the UAB Pediatric NF Clinic
The UAB Neurofibromatosis Clinic provides comprehensive, integrated care to adult and pediatric patients with all forms of NF, including NF1, NF2, and schwannomatosis. Because pediatric patients frequently have health concerns that are different from those of adult patients, we provide a dedicated pediatric NF clinic that delivers specialized care for pediatric patients from a multidisciplinary team of specialists who collaborate in the treatment and management of NF and its complications. This month’s blog features insight from two physicians who provide care to pediatric NF patients.
Read moreUAB NF Program Overview and Updates
This month’s blog post launches a series highlighting the three main categories that comprise our UAB NF Program – clinical care, research, and education. I’ll provide an overview of our program in these areas, while upcoming posts will give more in-depth information about specific aspects of the program and feature insights from our clinicians and scientists.
Read moreA Discussion of Genetic Penetrance and Variability of Expression in NF
Before beginning this month’s blog topic, I want to mention a couple of developments related to our UAB NF Program. First, one of the adult neuro-oncologists who worked with patients in our NF Clinic, Mina Lobbous, MD, recently left UAB for a position at another medical center. I know that many of our patients benefitted greatly from Dr. Lobbous’s expertise, and we wish him well in his new role. However, adult NF patients in our clinic still have the same access to specialists in the UAB neuro-oncology group, which assists NF patients with the management and treatment of NF-related neuro-oncological issues, including brain and spinal tumors and complex plexiform neurofibromas. In another development, we are planning a virtual UAB NF Symposium Family Day, scheduled to occur on Saturday, April 30. As we have for the past two years, we are holding this important event virtually this year to limit the spread of COVID-19. This free, half-day event, co-sponsored by the UAB Department of Genetics and the Children’s Tumor Foundation (CTF), gives patients and families the opportunity to hear a series of presentations on a range of NF-related topics from clinical experts. The agenda will be posted shortly on our UAB NF Program website (link) and Facebook page (link).
Previously, I have discussed the fact that NF is a highly variable condition that can express differently among affected individuals. For example, two people within the same family can have very different symptoms of the condition. In this post, I’ll briefly review the genetics and inheritance patterns of all forms of NF and discuss the primary reasons for variability in expression among people with NF.
Read moreA Discussion of Malignant Peripheral Nerve Sheath Tumors (MPNSTs)
The focus of this month’s blog post is a discussion of malignant peripheral nerve sheath tumors (MPNSTs), which represent one of the few potentially life-threatening complications of neurofibromatosis type 1. Because these tumors, which occur in about 10% of people with NF1, are not responsive to any known mode of treatment when they have spread through the body, early diagnosis and surgical treatment are currently important for a better outcome. Clinical trials are underway to identify more effective approaches to early detection and treatment.
Read moreExpanding Role of Telemedicine in the UAB NF Clinic
In early May, the UAB NF Clinic resumed in-person visits as the COVID-19 vaccine became widely available and cases decreased significantly in most parts of the U.S. However, due to the later resurgence of COVID-19 cases related to the Delta variant, UAB clinics were again encouraged to utilize telemedicine as much as possible to reduce viral transmission and protect patients. Before the pandemic, our NF Clinic had plans to integrate telemedicine into patient care. The explosion of the pandemic in early 2020 served to accelerate our adoption of telemedicine as a practical tool that allowed us to continue serving patients. As telemedicine continues to play an integral role in patient care in the UAB NF Clinic, I’d like to discuss the limitations and benefits of the technology as well as the potential role of telemedicine in the future of patient care.
Read moreA Discussion of Revised Diagnostic Criteria Released for NF1 and Legius Syndrome
In May, revised diagnostic criteria for NF1 were published in Genetics in Medicine, the journal of the American College of Medical Genetics and Genomics (Revised diagnostic criteria for neurofibromatosis type 1 and Legius syndrome: an international consensus recommendation | Genetics in Medicine (nature.com). The revised criteria are the product of a systematic, multi-year collaborative project of more than 90 NF experts from the international scientific community to arrive at a broad consensus.
Read moreResuming In-Person UAB NF Clinic Visits and a Discussion of the Frequency of NF Clinic Visits for Pediatric and Adult Patients
We are pleased that in-person visits have resumed in our UAB Adult NF Clinic each Thursday in the Whitaker Building and in our Pediatric NF Clinic on the second and fourth Tuesday of each month at Children’s of Alabama. To ensure the continued safety of patients and staff, requirements for masking and social distancing remain in place, and each person entering the clinic will also be screened for fever. We also plan to continue utilizing telemedicine visits because of the convenience and improved access this method provides our patients, particularly when reviewing test results or following up after an in-person visit. Because pre-pandemic licensing restrictions have been restored, our telemedicine visits are now limited to patients in Alabama and Florida.
As our UAB NF Clinics resume in-person visits for the first time since the start of the pandemic, this is a good time to address a question that patients frequently ask: How often should an individual with NF be seen in an NF specialty clinic? The answer is that the frequency of clinic visits depends on whether an individual with any of the three forms of NF is experiencing active problems that require frequent follow up. For example, regular clinic visits are part of the treatment plan for individuals taking the medication selumetinib. However, for people with NF who are stable and doing reasonably well, the general recommendation is to be seen by an NF specialist about once a year. While the guidance for an annual clinic visit is somewhat arbitrary, it is straightforward and easy to remember for most people and helps to maintain an active relationship with a care provider, as well as identify potentially treatable complications as early as possible.
In my experience, this guideline is generally well-followed for children with NF but less so for adults. There are several reasons for this, including the fact that parents often prioritize their children’s healthcare over their own. Also, NF can evolve rapidly in childhood, and it’s important for children to be monitored for the development of complications such as optic glioma, scoliosis, bone dysplasia, and plexiform neurofibromas. Another impetus for parents to have children seen annually is that most children are well-covered by either private insurance or Medicaid, whereas some adults may not have adequate insurance coverage for annual visits.
Adults with NF who are experiencing few active symptoms may question why it’s necessary to have an annual NF clinic visit. The rationale for yearly clinic visits for adults is that they provide an opportunity to catch the signs of serious complications such as malignant peripheral nerve sheath tumors (MPNSTs) or hypertension that might otherwise go unnoticed until they are advanced. Another reason to consider annual follow-up is to stay up-to-date on new advances in the field. For example, we now have access to clinical trials and even prescription medications, such as selumetinib, that did not exist a few years ago. Also, regular visits provide a way to stay in touch with the medical team so that they are familiar with a person’s history if problems eventually arise.
Because our goal is to help patients to be more proactive about their own care and encourage them to stay in touch with their NF care team, we may consider other options to make this easier for established patients, such as alternating annual in-person visits with telemedicine visits. This option might help ease the time and financial burden for many patients by giving them more flexibility and convenience. If something concerning arises during a telemedicine visit, we can schedule an in-person visit to follow up.
A Final Note
Just as this month’s blog was being completed, new diagnostic criteria for NF1 and Legius syndrome were published. This is an important advance in clinical care for NF patients. I will cover this in detail next month.