A Massachusetts General Hospital team (MGH) identified a deficiency in neural stem cells of patients with Huntington's disease. The discovery has allowed us to elaborate a new possible treatment.
The NRF2 transcription factor has the task of protecting cells from external damage. It activates the expression of antioxidant, anti-inflammatory and detoxifying genes. It also acts on all the genes that stimulate the elimination of damaged proteins. Researchers have found that NRF2 is, however, not present in neural stem cells of Huntington's sufferers.
A 2016 study identified a group of components that activates NRF2, called MIND4. MIND4 also inhibits the SIRT2 regulator enzyme, a strategy that has also produced excellent results against Parkinson's. The purpose now is to examine whether MIND4 activates NRF2 only in the guinea pigs or even in humans. If that were the case, it would have a great therapeutic potential.
The researchers also tested MIND4-17, a more powerful version of MIND4. In animal models, the compound increases the expression of antioxidant proteins. It also has the same process that activates NRF2 in response to oxidative stress. In this way, the transcription factor is not degraded by the disease and can activate antioxidant and protective genes.
NRF2 activation also produces anti-inflammatory effects. In particular, it acts on microglia and macrophage cells that penetrate the brain in the last stages of Huntington's disease. This reduces the levels of inflammation and also reduces the effects of the disease.
In Huntington's disease, the HTT gene has a repeated section repeatedly. The human neural stem cells of those suffering from the disease therefore present this problem. The more the repetitions are, the less NRF2 activation affects the symptoms. In cell lines where repetitions were reduced to non-pathological levels, however, activation was more effective. Same thing for non-neuronal cells, on which the effects of the compound were not influenced by the number of repetitions.
Further studies will be needed to test the efficacy of the compound first on animal models, then on the human being. If the tests were successful, there would be a possible treatment for Huntington's disease, Parkinson's and SLA.