Researchers at Tel Aviv University, led by Prof. Ilana Gozs of the Department of Molecular Genetics and Biochemistry at the School of Medicine and the Purple School of Neuroscience, uncovered a common mechanism for mutations in the ADNP and SHANK3 genes that cause autism and schizophrenia, among others. Prof. Gozes is effective in modeling animals with mutations in these genes and may be suitable for treating a variety of rare syndromes that impair brain function.
According to the researchers, the encouraging findings may lead to effective treatment of a variety of rare syndromes that impair brain function, and cause, among other things, autism, schizophrenia, and neurodegenerative diseases such as Alzheimer’s disease. The article was published in the prestigious journal Molecular Psychiatry.
Participants in the study were: Dr. Yanina Ivshko-Fahima, Maram Ghanaim, Inbar Ben-Horin-Hazak, Alexandra Lubintseva, Naomi Bleicha, Inbar Fischer, Gilad Levy, Dr. Shlomo Sargovich, Dr. Gideon Carmon, and others. Rabbi Eliezer Giladi from the School of Medicine and the Purple School of Neuroscience at Tel Aviv University, Dr. Boaz Barak from the School of Psychology and the Purple School of Neuroscience at Tel Aviv University, and Dr. Shula Shatzman from the Department of Mathematics and Computer Science at the Open University.
Prof. Gozes: “Autism is caused in some cases by mutations in various genes. Currently, more than 100 genetic syndromes associated with autism are known, of which about 10 are considered relatively common. In our laboratory we mainly study one of them, ADNP syndrome – caused by A mutation in the ADNP gene, which disrupts the function of the protein ADNP and impairs the skeletal structure of nerve cells in the brain. Autism worldwide. “
In the first phase of the study, the researchers took cells from patients with ADNP syndrome. They found that when the protein ADNP is damaged, nerve cells are formed with damage to the skeletal structure, which disrupts brain function. However, they found that there are different types of mutations in ADNP, and in some of them the damage is less.
Prof. Gozes explains: “We found that certain mutations add a section to the ADNP protein that protects it and reduces the damage through a link to a control site of the cellular skeletal system. Among other things, this control site is known to exist in SHANK3. “We concluded that the ability to bind to SHANK3 and similar proteins provides some protection against mutation damage.”
Next, the researchers found additional sites across the ADNP protein that could bind to SHANK3 protein and similar proteins. One of these sites was located in the NAP section, which is used as an experimental drug (called Davunetide) that was also developed in Prof. Gozes’ laboratory.
Furthermore, the researchers showed that long-term treatment with the experimental drug resulted in a positive improvement in the behavior of the model animals with autism caused by a mutation in SHANK3.
Prof. Gozes: “In previous studies we have shown that the drug is beneficial in case of ADNP syndrome. Following the new study, we believe the drug may be beneficial in case of Phelan McDermid syndrome where 3SHANK is mutated and also in other syndromes that cause autism in the joint mechanism.”
The experimental drug Davunetide has been granted orphan drug status by the FDA for future treatment of the rare developmental syndrome ADNP. The drug is protected by a variety of patents at Ramot, near Tel Aviv University. In collaboration with Professor Gozs as the lead researcher and business entrepreneurs, Atid – ATED – Therapeutics was established to develop Devontid for rare autistic syndromes on the one hand and other common brain diseases on the other.