Selumetinib is in clinical development for children with neurofibromatosis type 1 (NF1), also called von Recklinghausen’s disease. NF1 is a rare genetic disorder characterized by the development of multiple benign tumours of nerves and skin and areas of abnormal skin colour. NF1 is caused by mutation in a gene that regulates the production of a protein known as neurofibromin which is thought to function as a tumour suppressor. At birth or early childhood, affected individuals may have relatively large, benign tumours that consist of bundles of nerves and other tissue. These are known as plexiform neurofibromas (PNs). PNs may cause ongoing pain, motor dysfunction and disfigurement. Surgery may be used to remove PNs, but at high patient risk with the possibility of re-growth.
Selumetinib blocks an enzyme that is part of a signalling pathway in cells which can cause cells to grow, divide and copy themselves in an uncontrolled manner and may result in tumour growth. This pathway is improperly activated in patients with NF1, leading to the growth of tumours. Early studies have demonstrated the ability of selumetinib to shrink large tumours through its action on this pathway. Selumetinib may also aid in the improvement of health problems associated with PNs such as pain and motion problems. If licensed, selumetinib taken orally may provide the first pharmacological treatment option for NF1 and inoperable PNs.
Fenfluramine belongs to a class of drugs called the selective serotonin releasing agonists which stimulates multiple 5-HT receptor sub-types through the release of serotonin. Fenfluramine may also act on other receptors and these actions may help to reduce the frequency of seizures. When added to other standard anti-epileptic treatments, fenfluramine hydrochloride has shown preliminary evidence of reducing seizure frequency. If licensed, fenfluramine hydrochloride may offer an additional treatment option for patients with Lennox-Gastaut syndrome.