Restless legs syndrome (RLS) is a very rare but debilitating neuromuscular disorder. Treatment options for RLS are limited and the prognosis is poor. However a study led by Professor Iwamoto Yutaka and Dr. Shizuka Sakamoto from Team Nara Institute for Medical Research has revealed that an electrical stimulation method to modulate GRN3B is as effective in blinding RLS as a pharmacological treatment. An article published in Nature Communications reveals that the procedure is effective at inducing mild central nervous system depression and significantly alleviates symptoms.
As RLS is defined by a mutation in the gene GRN3B the gene encoding the GRN3B protein is mutated in about 1 of cases. Due to this mutation RLS patients have a genetic alteration in the GRN3B protein. This identifies RLS patients as having a mutation in the GRN3B protein leading to symptoms of GRN3B malfunction and a lack of control over the GRN3B protein in the brain. Central nervous system depression is a common cause of RLS which may be contributing to the worsening of ARDS (arthral neurovascular disease).
We started our exploration of GRN4L-3 inhibitors by applying the electrophysiological measurements of GRN3B fusion in a mouse model and observed that GRN3B mediated the feeding and feeding behavior of the mice through GRN3B fusion activation. We then applied the same approach in ARDS rats and observed that GRN3B fused activation produced enhanced behavioral responses. Finally we investigated the efficacy of GRN3B probe in shooting this HMGA2-mutant rat. After 10 weeks we found that GRN3B fused activation activated 60 more GRN3B receptor potentials than current pharmaceutical GRN3B-targeted drug therapy. This triggered the rats to self-administer more drug resulting in complete hyperikritamine tolerance. Thus GRN3B-targeted drug persists even in areas of severe RLS for which therapy is insufficient (CAR T-cell therapy). This finding excited us to test the feasibility of GRN3B stimulation in ARDS patients.