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Experimental Drug Shows Promise as Autism Treatment, Study Discovers

Researchers from Tel Aviv University in Israel have discovered that an experimental drug could effectively treat a range of rare syndromes that impair brain functions.

The research team found that a mechanism shared by mutations in the genes ADNP and SHANK3 are linked to autism, schizophrenia, Alzheimer’s disease, and other brain disorders. The findings were published recently in the scientific journal Molecular Psychiatry.

Led by Professor Illana Gozes from the department of human molecular genetics and biochemistry, the team found that an experimental drug known as davunetide worked effectively in animal models. The patent-protected drug, which was developed by Gozes’ lab, was recognized by the Food and Drug Administration as an “orphan and rare pediatric drug” that could in the future effectively treat the ADNP syndrome, which is linked to autism and schizophrenia.

Davunetide has been exclusively licensed to ATED Therapeutics, where Gozes is the chief scientific officer.

“We now know that davunetide can maybe also help in autism syndromes that contain the mutation in SHANK3,” Gozes told The Media Line. “In the case of the ADNP syndrome and also in the case of SHANK3 mutations, patients also suffer from intellectual disability. It’s not only a social deficit; it’s also a massive developmental deficit and intellectual disabilities. The drug candidate stimulates learning and memory, and also works on the social deficit.”

According to Gozes, the encouraging results could lead to effective treatments for a wide range of rare syndromes that cause brain disorders.

The research deepens our understanding of why certain genes lead to autism. What we’re trying to do is improve our understanding of what happens in the brain and in cells that make up the brain when these genes are faulty.

Gozes, who is also the director of the Adams Super Center for Brain Studies at Tel Aviv University, noted that some forms of autism are caused by genetic mutations.

In order to carry out the research, scientists obtained cells from patients with ADNP syndrome. They found that when the ADNP protein is defective, neurons with faulty skeletons (microtubules) develop and impair brain functions. They also discovered that some ADNP mutations cause less damage.

“We discovered that, in some mutations, a section added to the protein protects it and reduces the damage by connecting to a control site of the neuron’s skeletal system,” Gozes explained.

“We concluded that the ability to bond with SHANK3 and other similar proteins provides some protection against the mutation’s damaging effects,” she said.

Over the course of the research, scientists discovered that extended treatment with davunetide significantly improved the behavior of animal models with autism caused by SHANK3. There is currently no available treatment for ADNP syndrome.

“Today we know of more than 100 genetic syndromes associated with autism, 10 of which are considered relatively common,” though still extremely rare, Gozes said. “In our lab we focus mainly on one of these, the ADNP syndrome, caused by mutations in the ADNP gene, which disrupt the function of the ADNP protein, leading to structural defects in the skeleton of neurons in the brain.”

The next step, Gozes said, is to conduct clinical trials of the drug on humans at ATED Therapeutics. The drug has already been tested on some humans and has been shown to be safe and well-tolerated.

Ultimately, the findings could pave the way forward for a broader treatment of brain disorders, according to Dr. Boaz Barak, a senior lecturer at Tel Aviv University’s School of Psychological Sciences who specializes in neurodevelopmental disorders and who also took part in Gozes’ research.

“The research deepens our understanding of why certain genes lead to autism,” Barak told The Media Line. “What we’re trying to do is improve our understanding of what happens in the brain and in cells that make up the brain when these genes are faulty. If we can know what is wrong in the cells, then we can figure out what needs to be fixed.”

The drug the researchers administered to the model animals carrying the mutations in question led to behavioral improvements for autism, Barak added. Nevertheless, the research is still in its infancy and a full treatment could take several years to develop.

“Because the causes of autism are very diverse, and include genetic causes related to hundreds of different genes as well as nongenetic risk factors, it is very important to focus on developing treatments in accordance with the causes that led to autism,” Barak said.