Global Network of Neurofibromatosis Patient Organisations

Meeting, Research

Highlights from the global 2019 NF Conference in San Francisco

CTF-NF Conference

On September 21-24, 2019, the Global NF Conference was held in San Francisco, USA. This year the global NF scientific meeting attracted over 500 NF experts, researchers, and clinicians, among which NFPU members were also present.

The participants discussed an array of topics including chronic pain, psychosocial issues, genetics and biology of cancer, mindful-based stress reduction, imaging techniques, gene editing, and many others.

Below are some highlights from the conference courteously provided by several contributors.

Disclaimer: all materials are for information only and are based on voluntary contributions not verified by medics. These materials cannot be used as a basis or as a part of any decision-making, or interpreted as an advice or recommendation to proceed with, or to abstain from any treatment options described below.

1. Research and access to data

The amount of NF research is significantly increasing. There are currently 214 studies reported in (USA), among which 54 are actively recruiting trials and 92 are studies competed. There are 17,078 related publications on Pubmed. The positive news is an expanded role of patient advocacy groups. Everyone agreed though that the group that is massively underrepresented in the literature are the family and caregivers.

There is a growing need for patient registries and bio-repositories as the sources of gathering important data. It is also necessary to ensure global access to the data in order to have a positive impact on multicentre studies, and facilitate dissemination of the information to the community. The overarching focus should be on maintaining commitment and empathy to patients, with a special focus on the mental, physical and financial health of caregivers.

2. Cognitive and social development in NF1

There have been a few studies on cognitive development in NF1, but few of them have been performed on younger children, and this is why natural history of cognitive development during early childhood is poorly understood. There need to be more studies that focus on children under the age of 8 with NF1 to investigate their particular challenges. A study in Vienna is currently collecting data and will publish the results soon to see at what age difficulties may occur and how to support children at preschool age.

Social difficulties that children with NF1 have now receive greater attention. Researchers looked at the quality of their relationships (how well liked they are by their peers), their interactions and ability to take turns in conversation, and their ability to be flexible and adapt to the demands of the social environment. Some had decreased ability with complex perspectives – taking social cues and interpreting facial expressions (especially fear and anger). This was said to be more common in males with NF1.

The longitudinal study from 2005 – 2019 looking at cognitive development from early infancy through early childhood was presented. Neurodevelopmental assessments were performed at 5 months, 9 months, 15 months, 21 months, 30 months, 40 months, 5 years and 7 years. It demonstrated that mean cognitive scores in NF1 patients were significantly lower than in the control group, though afterwards NF patients normally follow the similar pattern over time. Three clusters within the NF group were identified: one cluster whose cognitive development was similar to controls, another cluster whose development was consistently below average and another that was average and then declined from 5 years onwards, where more research has to be performed to discover the reasons. At the age of 7 years children with NF1 had a 4 times higher risk to have an impaired word reading than controls. No difference between genders was reported, but higher parents socio-economic status (SES) and sporadic NF tended to be associated with average/higher IQ. The analysis is still ongoing with plans to follow up the NF cohort now focusing on the age 8-16 years.

Generally, children with NF1 are at a massive risk of psychosocial morbidity that needs to be addressed. Therefore a working group was formed to create psychosocial guidelines regarding the different psychosocial problems, from standardized diagnostics to treatment. The group is now beginning to perform a systematic review of the literature including the last years (2013-2019). Electronic databases such as PubMed, PsychINFO and SCOPUS shall be covered. Studies addressing diverse psychosocial aspects of NF are going to be included. Moreover medical advice regarding psychic problems (e.g. Autism, ADHD, etc.) should be given. As different age groups have different problems two papers, will be published: one focusing on psychosocial issues and how to encounter these with regard to childhood and adolescents, and another paper focusing on adults needs and concerns.

3. Selumetinib

Selumetinib, a medicine that inhibits MEK1/2, was tested in a phase II trial, and it was said to improve a range of motion and physical activities for some of the children. In this research so far, no patients had disease progression. However, few side effects were noted, for example rashes. In general, the use of Selumetinib demonstrated the ability to kill mutant Schwann cells and clinical benefit in adults with symptomatic NF1-associated plexiform neurofibromas that are growing or causing morbidity. It was also reported that Selumetinib reduced pain.

4. Diagnostics and imaging

The Stanford team presented a combined PET-MRI scan that allows producing combined images that show more clearly tumour boundaries, relationships with blood vessels, as well as metastasis. They use an iron injection as contrast so no radiation is involved, and the contrast is simply metabolized over several weeks.

Another team presented their findings, according to which radionics and artificial intelligence in quantitative imaging analysis provide more accurate, efficient, objective, comprehensive and automated imaging bio markers which allows for better management of NF patients in clinical oncology.

Another research was aimed at proving that the contrast does not change the interpretation of neurofibromas (benign vs malignant) in the vast majority of patients, therefore, using less contrast could mean avoiding unnecessary side effects and risks to patients. Spinal neurofibromas, however, were outside the scope of the research.

5. Schwann cells and pain

A recent science paper identified a new potential contributor to the activity of pain: Schwann cells. Schwannomatosis is characterized by severe pain and the development of numerous tumours comprised of abnormal Schwann cells on peripheral nerves. Schwann cell pain is not always associated with the presence or the size of the tumour. Schwann cell pain can persist despite aggressive medical or surgical treatment. Hypothetically, LZTR1 and SMARCB1 could directly influence the secretomes that cause pain. In other words, when stimulated these cells induce pain. This is interesting finding that requires more research.

CTF-NF Conference

6. Acceptance and Commitment Training

There was a presentation on ACT – Acceptance and Commitment Training. Its aim is to increase people’s acceptance of their pain, which often impacts the quality of their life. ACT can allow increasing the so-called “value time”, i.e. time spent with families and friends and on hobbies. Participants of the program were taught mindfulness methods to use when upset or in pain, and later they reported less pain intensity. ACT is also cost-effective because the researchers needed only four hours to meet each participant in person to teach them various ACT methods, and then they subsequently sent out emails, audio files and apps for participants to use.

7. NF-tailored mind-body program

There was a presentation of a trial online mind-body program for coping with stress and improving resilience in people with NF.
More information can be found here:
Recruitment for the trial will close in May 2020. To be recruited please follow the link

8. Treating pain

Complementary and integrative health (CIH) therapies for pain were reported to be increasingly helpful and gathering increasing evidence of success. They contribute to the mindfulness-based stress reduction. Among them are various mind-body therapies, such as: hypnosis, meditation, biofeedback, yoga, tai chi, therapeutic massage, acupuncture, chiropractic, art therapy, music therapy, relaxation training, healing touch, movements, etc. Some of them have been recognized as medical therapies in the USA. NIH 2016 review of evidence for pain found the following complementary approaches to have positive effects: acupuncture and yoga for back pain, acupuncture and tai chi for osteoarthritis of the knee, massage therapy for temporary neck pain relief, relaxation techniques for severe headaches and migraine.

9. Autism and anxiety in NF patients

There is a higher prevalence of autism in patients with neurofibromatosis. NF affects brain development with abnormalities in apoptosis and pruning of synapses. There is a high percentage of severe autism cases among NF adults.

Reports were collected from caregivers of children with NF1 at ages 3 and 6 years. There were more problems with school age than pre-school children, although this was not always clear why. Again, there were differences in caregivers and children’s reports. There needs to be more research to look if anxiety is more of an issue for adolescents. NF1 children have higher symptoms of anxiety and attention problems, worse at school age than early childhood. NF1 have greater symptoms of generalized anxiety, social anxiety, physical injury fears and separation anxiety at school age compared to early childhood.

Regardless of NF type, patients with NF1 have similar psychological profiles characterized by greater emotional distress, pain and suicidality. Current management is primarily through surgical and palliative interventions. Less attention paid to psychosocial factors, yet patients benefit most from biosocial psychological approach.

10. Neurofibromas

Neurofibroma visibility is said to be the major source of burden for patients. Anxiety and depression are directly linked to the visibility of the disease. Age is a risk factor for the number of neurofibromas. There is off-label use of Trametinib to treat neurofibromas, and reportedly it makes those decrease in number and size. However, trials are still ongoing to discover the full potential and side effects of such use.

Multiple questions surrounding acceptability of interventions for cutaneous neurofibromas were raised in view of the fact that patients are often not satisfied with the regrowth, scars, or the frequency of the intervention. 

11. The Precision Health Future

The aim of the Precision Health Future is to predict, prevent and cure. Free DNA sampling of cancerous DNA helps with prediction, and methods such as CRISPR/Cas9 gene editing are beginning to show some promising results in some monogenetic disorders. CRISPR (clustered regularly interspaces short palindromic repeats) dates back to 1987. In 2012, Cas9-guide system was created. Over the last 7 years, it has been improved and gene editing techniques have expanded the field of functional genomics. In the longer term, CRISPR-Cas9 has the potential to be curative for a range of genetic conditions, including NF. For example, it is used to better understand genesis of tumours, often using Scwann cells, where malignant peripheral nerve sheath tumours (MPNSTs) are present.

The question was raised of what is an acceptable level of risk for gene therapy and who should decide on it from the ethical perspective: clinicians, the ethics board, patients and so on.

12. 2019 Friedrich von Recklinghausen Award

NFPU also wishes to use this opportunity to congratulate Scott Plotkin MD, PhD, on winning CTF’s Von Recklinghausen award this year. Scott Plotkin is director of the Family Center for Neurofibromatosis at Massachusetts General Hospital and a Professor of Neurology at Harvard Medical School. He has a distinguished record of NF2-related research. So well deserved!

13. REiNS

The REiNS meeting took place on Sunday, October 22, 2019. The different groups presented their recent results for further discussion. The working group on neurocognitive outcomes is currently finishing their review of social measures and completing the manuscript. The preschool subgroup has reviewed preschool measures of attention. They are focusing on parent questionnaire and interviews. The next focus of the working group will be on autism-like behaviors and broader social functioning (and when to recommend these measures). The team is also considering whether to include computerized measures rather than paper-pencil questionnaires for cognitive tests.

The patient reported outcomes (PRO)-group has completed manuscripts for general quality of life (QoL) and disease-specific QoL. They are about to launch a survey for psychosocial trials and outcomes in the next months. The communications subgroup is ready to publish recommendations on hearing PROs for NF2 patients. After the 2020 supplement is complete, the team will meet to consider direction of the committee since they have completed review of 4 domains initially identified as focus. The working group of patient representatives is currently focused on assessing the success of the patient rep program within REiNS. The goal of this assessment is to strengthen the overall Patient Rep program. A survey was provided to patient representatives with a response rate of 68%. A second survey to all REiNS members was circulated and achieved a 33% response rate.

The working group on cutaneous neurofibromas has completed a survey on attitudes towards cutaneous neurofibroma (cNF) in more than > 500 adults with NF1. A draft manuscript is being circulated, and a parallel survey of adolescents and caregivers is being designed. The group also has a final manuscript describing PROs related to cNF using Skindex for Australian patients and US patients. The cNF biomarker group is working on a manuscript summarizing use of biomarkers for cNF research.

The team on diseasebiomarkers has been focused on incorporating patient representatives into the working group. Together, they are working on a manuscript that describes use of genetic biomarkers in NF. With regard to functional outcomes, this working group is studying the reproducibility of hand-held dynamometry to measure strength in patients with NF1, NF2, and Schwannomatosis. This study is being conducted by the team at NYU. 29 of 40 patients have been recruited to date and preliminary results suggest that HHD is a reliable technique for use in NF clinical trials.

The 2019 Winter REiNS Meeting will be held on:
Monday, December 9, 2019 in Baltimore (Maryland).

The Abstract Book from the conference is available here: