In light of the findings, the researchers tested an experimental drug called NAP – developed for Alzheimer’s disease – on nerve cells in a model for ADNP syndrome with Alzheimer’s-like symptoms. The experiment was crowned a success, and the damaged nerve cells returned to normal function.
The study was conducted in close collaboration with researchers from the Belvatnik School of Computer Science at Tel Aviv University, researchers from Sheba Medical Center and a variety of research institutions across Europe: BIOCEV Institute of Biotechnology in the Czech Republic; Aristotle University in Thessaloniki, Greece; University of Antwerp in Belgium; , Croatia.The article was published in July 2020 in the journal Translational Psychiatry from Nature.
Turn the wheel back
Prof. Gozes explains that the current study is based on tissues taken from the brain of a 7-year-old boy with ADNP syndrome, who died in Croatia. When we compared them to tissue from the brain of a young person who does not suffer from ADNP syndrome, we found in the child a deposition of the tau protein, known as a characteristic of Alzheimer’s disease. The researchers then ‘treated’ the damaged nerve cells with a drug called NAP, which was developed in Prof. Gozes’ laboratory and is intended to be used as a cure for Alzheimer’s disease. “NAP is actually a short section of normal ADNP protein,” notes Prof. Gozes. “When we added the NAP to the neurons representing a mutation in ADNP, the tao protein returned to bind to the cell skeleton properly, and the cells returned to normal function.”
Towards the clinical trial phase
“The fact that NAP treatment has been able to restore neuronal cell-like cells with impaired ADNP to normal functioning raises hopes that this substance may be used as a remedy for ADNP syndrome and its severe consequences, including autism.” Says Prof. Gozes, “Moreover, because other genetic syndromes associated with autism are also characterized by dysfunction of tau protein in the brain, we hope that those with these syndromes will also be able to benefit from NAP treatment in the future. It is important to note that NAP (also called CP201) has been labeled ‘ An orphan disease drug from the FDA – the US Food and Drug Administration, and it is currently in the preparation stages for a clinical trial in children with ADNP syndrome through the commercial company Coronis Neurosciences.
In another phase of the study, the researchers sought to broaden their understanding of the effects of the mutation that causes ADNP syndrome. To do this, they extracted the genetic material mRNA (RNA messenger) from the tissues of the deceased child, and performed an expression of about 40 proteins of that child, encoded by the mRNA. Full genetic sequencing was also performed to determine protein expression in white blood cells taken from three other children with ADNP syndrome. On all the data obtained in the genetic sequences, an in-depth study was performed using advanced computational tools of bioinformatics. The data were compared to online databases of protein expression data in healthy individuals, thus revealing a variety of characteristics common to sick children but very different from the normal occurrence of those proteins.
Prof. Gozes concludes that “the findings mean that the mutation that causes ADNP syndrome impairs a wide range of essential proteins, many of which bind to, among other things, tau protein, and also impair its function. This creates various pathological effects in the brain (and other tissues) of children with ADNP syndrome. “It is the creation of tau sediments, known as characteristics of Alzheimer’s disease. The vast and in-depth knowledge we have accumulated through the present study opens the door to further, extensive and diverse research work. We hope and believe that in the end we will reach the goal: drug development.”