Neurofibromatosis Type 1 (NF1) is one of the most common genetic disorders that causes
learning disabilities. In NF1 loss of function mutations of neurofibromin causes RAS-pathway
hyperactivity, leading to deficits in long-term potentiation (LTP), a basic mechanism
of learning and memory in the mouse model. Recently, it was shown that inhibition
of HMG-CoA reductase by Lovastatin rescues these deficits in mouse models of NF1.
The presented study shows that humans with NF1 have impaired LTP-like plasticity and
that this impairment can be improved by Lovastatin.
11 NF1-patients (mean 28.0±9.2 years, 4 female, 7 male) and 11 healthy volunteers
(mean 24.72±3.58 years, 5 female, 6 male were studied using paired associated stimulation
(PAS), a TMS protocol commonly used to induce LTP-like plasticity. Furthermore the
effect of 200mg Lovastatin on LTP-like plasticity induced by PAS was investigated.
We demonstrated that, one hour after PAS, MEP amplitudes of healthy controls did increase
significantly from 1.0±0.17 to 1.71±0.48 mV (Post 3: p=0.001, paired t test) compared
to patients with NF1 (1.05±0.22 to 0.92±0.56 mV) and that there was a significant
difference between both groups at this point in time (p=0.000, unpaired t test). Moreover,
after administration of Lovastatin, MEP-amplitudes significantly increased immediately
(from 0.84±0.47 mV to 1.44±0.52 mV; p=0.016, paired t-test) and 30min (from 0.80±0.41
mV to 1.31±0.63 mV; p=0.041, paired t-test) after PAS in patients with NF1. In conclusion
LTP-like plasticity in NF-1 patients is impaired and Lovastatin may prove useful in
the treatment of Neurofibromatose Type 1.
