Rare genetic disorders: The first steps to celullar human models

Nowadays, we have been able to see new rare genetic disorders that need to be studied carefully to detect which phase of the development is affected; and more importantly, how it can affect to subsequent pathways. Knowing this can be very useful to detect molecules that can be a target for the development of potential new drugs.

There are plenty of genetic disorders. However, one rare genetic disorder named as Rett syndrome affects the normal development of the brain, mainly in kids. This is a progressive neurological disorder caused by mutations in the X-linked gene encoding MeCP2 protein (Amir et al., 1999). The subject may apparently have normal development until 6-18 months of age, until the impaired motor function becomes very notorious, stagnation and then regression of developmental skills, hypotonia, seizures and autistic behavior (Amir et al., 1999). RTT patients have a large spectrum of autistic characteristics and are considered part of the ASD population.

Autism spectrum disorders (ASD) are complex neurodevelopmental diseases in which different combinations of genetic mutations may contribute to the phenotype. Using Rett syndrome (RTT) as an ASD genetic model, a group of scientists (Marchetto et al, 2010), developed a culture system using induced pluripotent stem cells (iPSCs) from RTT patients’ fibroblasts. These pluripotent human embryonic stem cells (hESCs) have been successfully generated from early stage human embryos and are able to differentiate into various cell types. However, to be able to develop cellular human models is necessary to generate cell lines with genomes predisposed to diseases. Recently, reprogramming of somatic cells to a pluripotent state by overexpression of specific genes (induced pluripotent stem cells, iPSCs) has been accomplished. The generation of a cellular human model can be very useful to study a specific group of diseases such as the ASD, so the scientists can find the common molecules that are affected and may find a potential treatment.

There is so much left to do, but the first steps to create cellular human models to these types of diseases have been made, and it will be very useful to other types of genetic diseases that are really complex, and that the use of animal models is no longer enough to fully understand how these diseases are generated.

Here in Althian we have several protocols that have potential treatments that have demonstrated efficacy and safety. However, as any other drug, they can generate several adverse events. That’s why it is important to be aware of everything once a protocol has begun, so the patient can receive the attention he needs. Please contact us and we will more than happy to explain you how we work.