Science & Technology

Breakthrough experimental compounds show efficacy in the treatment of symptoms of autism and Alzheimer’s disease

Designed by the FDA as orphan drugs and pediatric rare diseases, experimental compounds are effective in treating autism and the symptoms of autism. Alzheimer’s disease disease.

  • Researchers have developed a new model to evaluate the effect of this experimental drug on symptoms associated with autism, intellectual disability, and Alzheimer’s disease, with a short protein segment called NAP treating a wide range of symptoms. I found.
  • Symptoms improved using NAP: slow development, lack of communication, brain with relatively low synaptic numbers, decreased electrical activity, protein aggregation similar to that seen in patients with Alzheimer’s disease.

In an extensive international study led by the University of Tel Aviv, experimental drugs designated by the FDA for the future treatment of rare developmental disorders are also associated with autism, intellectual disability and Alzheimer’s disease. It turns out that various symptoms can be treated.

The experimental drug NAP was discovered in the laboratory of Professor Illana Gozes, Department of Human Molecular Genetics and Biochemistry, Tel Aviv University Sackler Medical College. In recent years, the FDA has approved experimental drugs with orphan drug designations and pediatric rare disease designations for the treatment of a rare developmental disorder called ADNP syndrome that can cause a variety of symptoms. Its characteristics are intellectual disability and autism spectrum disorders. hindrance.

In the current study, a team of researchers led by Professor Gozes has developed an innovative lab model and found that NAP may be effective in treating a wide range of symptoms of ADNP syndrome caused by mutations in the ADNP gene. Did. Brain development and protection of brain cells. Previous studies have shown that ADNP syndrome is associated with Alzheimer’s disease and certain types of psychiatric disorders, developmental delay, and autism.

Illana Gozes

Professor Illana Gozes.Credits: Jonathan Blum, Tel Aviv University

Ramot, a technology commerce company at Tel Aviv University, has applied for numerous patents to protect technology and its implementation, and is working with Professor Gozes to raise funds to fund further clinical research. .. Similarly, Ramot is discussing commercial cooperation with pharmaceutical companies. Professor Keren Primor Cohen, CEO of Ramot, said:

The culmination of PhD research by Dr. Gideon Carmon, an MD / PhD student, was attended by a team of researchers in Professor Gozes’s lab. Dr. Oxana Kapitansky, Dr. Alexandra Lubincheva, and Dr. Eliezer Giladi. The team also includes Dr. Moran Rubinstein, Professor Noam Shomron, and Guy Shapira of TAU’s School of Sackler Medicine, and Dr. Metsada Pasmanik Chor of the George S. Wise School of Life Sciences at Tel Aviv University. Researchers from the Czech Republic, Greece, Germany and Canada also participated.The article was published in a prestigious journal Biological psychiatry.

Professor Gozes explains: “In fact, NAP is made up of short segments of normal ADNP protein. It was previously discovered that treatment with NAP modifies the function of human neurons suffering from ADNP syndrome in laboratory tubes. This study investigated the effectiveness of NAP in treating various aspects of the syndrome using models with the most detrimental mutations, thereby observing brain development and behavioral. I was able to help improve the problem. “

This study, which examined the model using mice with ADNP syndrome, used objective methods to analyze behavior and electrical activity to further identify selected protein content in the brain. Researchers found that mice suffering from ADNP syndrome showed a wide range of pathological outcomes, including increased neonatal mortality immediately after birth, delayed development, predominantly female gait abnormalities, and decreased voice communication. bottom.

Examination of the brain showed additional findings. Relatively few synaptic-nerve contact points, impaired electrophysiological activity indicating a low likelihood of normal brain arousal, and tau protein precipitates (aggregates) in young mice in aged Alzheimer’s disease Things in the patient’s brain.

For most of these symptoms, researchers investigated the effects of the future drug NAP, which is made up of short, normal segments of the ADNP protein, the same protein that is compromised by mutations. Professor Gozes: “In the past, we discovered that NAP corrects dysfunction of mutated ADNP in a neuronal model in culture. We have now investigated its effect in vivo – Syndrome (ADNP mutation). In the animals to be modeled. To our surprise and joy, we found that treatment with NAP normalizes the function of these mice for most of the above symptoms! “

Researchers have also sought to identify clear biological indicators of ADNP syndrome in the blood of mice that enable the diagnosis of this serious disease and the effective monitoring of treatment using simple blood tests. bottom.With the help of gene sequencing technology, they identified abnormalities in a way that was unique to females only, and identified how to repair five proteins (in messenger) using NAP. RNA level). These findings were consistent with the changes found in white blood cells in children suffering from ADNP syndrome. One of the indicators discovered is FOXO3. It is a protein that plays an important role in the production of brain synapses and healthy aging.

Professor Gozes summarizes: “This study examines the effects of the most common mutations in the ADNP gene in a wide range of ways, including autism, developmental delay, psychiatric disorders, and Alzheimer’s disease in humans. Similarly, NAPs for treating these diseases. We investigated the potential use of the drug and found in a lab model that it was effective against most of these symptoms. This study found that patients with Alzheimer’s disease as well as autism due to genetic mutations. It’s an important milestone in developing one or more medicines to help children in the world. “

Reference: “New ADNP Syndrome Mice Reveals Dramatic Sex-Specific Peripheral Gene Expression with Brain Synapse and Tau Pathology,” Gidon Karmon, Shlomo Sragovich, Gal Hacohen-Kleiman, R. AnneMcKinney, Moran Rubinstein, and Illana Gozes, September 27, 2021 Biological psychiatry.
DOI: 10.1016 / j.biopsych.2021.09.018

Breakthrough experimental compounds show efficacy in the treatment of symptoms of autism and Alzheimer’s disease Breakthrough experimental compounds show efficacy in the treatment of symptoms of autism and Alzheimer’s disease

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