We have recently established central auditory difficulties as a common feature of NF1. The severity of these difficulties was significant enough to cause impairing disruptions to children’s everyday communication abilities and academic progress. This talk will briefly review the evidence for these difficulties and introduce the TAPiN trial, which is a four-week randomised crossover study followed by a controlled 30-week extension, which was recently funded by the Medical Research Future Fund. 

Study outcomes are clinically meaningful and include measures of speech perception, literacy skills, attention, fatigue, social function, and quality of life. Recruitment for this study has recently commenced at the Murdoch Children’s Research Institute and The Children’s Hospital at Westmead. This study is expected to provide evidence for a novel, non-invasive intervention targeting a common and impairing problem in NF1.

We reviewed files from the clinic to see if diagnostic standards were upheld, what the incidence was in this population compared to non-rasopathy patients, which ADHD treatment was commenced and if there was recorded evidence of efficacy as provided by school reports, parental reports and other factors such as socialisation, depression and anxiety. 

The results showed a higher incidence of ADHD in this group of patients but equivalent efficacy. This was a retrospective and qualitative audit. This audit will hopefully convince administrative staff that ongoing funding for such a clinic is justified.  

We’ve established a preclinical mouse model of NF1, to understand the pathogenic mechanisms mediating autism, ADHD, learning difficulties and other psychiatric and cognitive symptoms commonly seen in this condition. 

The long-term aim of this research is to assess novel therapeutic approaches specifically targeting these aspects of NF1, which significantly impact quality of life, but which remain unaddressed by current treatment strategies. This Nf1 +/- mouse model involves a heterozygous null gene mutation in the mouse neurofibromin gene (Nf1), the human homologue of which is mutated in patients with NF1. 

We’ve performed a wide range of mouse behavioural tests and have been able to replicate previously published findings that have shown these mice have a deficiency in spatial learning, short-term memory and altered sociability, as well as increased brain weights. Nf1 +/- mice also showed differences in body weight trajectory which may be related to metabolic differences, which are also highly relevant to NF1 patients. Intriguingly, several gastrointestinal organs were also found to be anatomically changed in Nf1 +/- mice. 

In further work, we will perform further cutting-edge cognitive tests in this mouse model, which can identify subtle cognitive deficits and which are directly translatable. Ultimately, candidate drugs (guided by our clinical NF1 collaborators in Melbourne) will be trialled in these mice to assess their preclinical efficacy in correcting cognitive and psychiatric behavioural symptoms. 

Discussion on session 4