NAP, an experimental drug revealed by a large international study conducted by the UTel Aviv University and that it has obtained orphan drug designation from FDA for future treatment of a rare developmental disorder may also treat a variety of symptoms related toautism, at the intellectual disability and al Alzheimer’s disease.
The results of the Research have been published in the scientific journal Biological Psychiatry.
NAP: a hope also for intellectual disabilities
The experimental drug NAP was discovered in Prof.ssa’s laboratory Illana Gozes of the Department of Human Molecular Genetics and Biochemistry of Tel Aviv University Sackler Medical School. In recent years, the FDA has granted the investigational drug orphan drug designation and pediatric rare disease designation for the treatment of a rare developmental disorder called ADNP syndrome, which can cause a variety of symptoms, the standout features being intellectual disability and autism spectrum disorder.
In this study, a team of researchers led by Prof. Gozes developed an innovative laboratory model and found that NAP can be effective in treating a broad spectrum of symptoms of ADNP syndrome, which is caused by mutations in the ADNP gene that it is essential for brain development and the protection of brain cells. Previous studies have shown that ADNP syndrome is related to Alzheimer’s disease and certain types of mental disabilities, developmental delays and autism.
Ramot, the technology trading company of Tel Aviv University, has filed a series of patent applications to protect the technology and its implementation and, in collaboration with the Prof. Gozes, is raising money to fund further clinical research.
Likewise, Ramot is discussing commercial collaboration with pharmaceutical companies. “We are excited about this new discovery and believe it is a revolutionary technology that will remedy a variety of symptoms and disabilities across a broad spectrum of orphan diseases. ” said prof. Keren Primor Cohen, CEO of Ramot.
The study, headed by Dr. Gideon Carmon, was supported by a team of researchers from Prof. Gozes’ laboratory: Dr. Shlomo Sergovich, Gal Hacohen-Kleiman, Inbar Ben-Horin-Hazak, Dr. Oxana Kapitansky, Alexandra Lubincheva and Dr. Eliezer Giladi. The team was also supported by Dr. Moran Rubinstein, Prof. Noam Shomron and Guy Shapira of the TAU Sackler Faculty of Medicine, and Dr. Metsada Pasmanik Chor of the George S. Wise Faculty of Life Sciences of Tel Aviv University. Researchers from the Czech Republic, Greece, Germany and Canada also participated.
The professor. Gozes explained that: “Indeed, NAP comprises a short segment of the normal ADNP protein. We previously found that NAP treatment corrects the function of human nerve cells affected by ADNP syndrome in a laboratory test tube. In this study, we sought to examine the effectiveness of NAP in treating various aspects of the syndrome using a model with the most damaging mutation, which allowed us to visualize brain development and facilitate resolution of behavioral problems. “
The study, which looked at a model using mice with ADNP syndrome, used objective methods to analyze behavior, electrical activity, and to further identify the selected protein content in the brain.
The researchers found that mice with ADNP syndrome demonstrated a broad spectrum of pathological outcomes, including increased rates of neonatal death soon after birth, slowed development and aberrant gait, mainly among females, as well as poor voice communication.
Brain examinations showed further findings: a relatively small number of synapses, points of contact between nerve cells, impaired electrophysiological activity that demonstrates a low potential for normal brain excitation, as well as precipitates (aggregates) of Tau protein in mice. young, similar to those in the brains of elderly patients with Alzheimer’s disease.
For most of these symptoms, the researchers looked at the effect of the future drug substance NAP, consisting of a short, normal segment of the ADNP protein, the same protein damaged due to the mutation.
Prof. Gozes explained: “In the past, we have found that NAP corrects the impaired functioning of ADNP that is mutated in the nerve cell pattern in culture. We have now examined its effect in vivo, in mice with the syndrome (ADNP mutation). To our amazement and delight, we found that NAP treatment normalizes the functioning of these mice for most of the above symptoms! “
The researchers also sought to identify a clear biological marker of ADNP syndrome in the blood of the mice that will allow diagnosis of this serious disease and effective monitoring of treatment using a simple blood test.
With the help of genetic sequencing technologies, scientists identified an abnormality in a way characteristic only of females, as well as a method for repair using NAP on five proteins (at the messenger RNA level).
These results matched the changes found in the white blood cells of children with ADNP syndrome. One of the indicators discovered is FOXO3, a protein with an important role in the generation of brain synapses and healthy aging.
The professor. Gozes stated: “In this study, we examined the effect of the more prevalent ADNP gene mutation in a broad spectrum of aspects and found extensive impairment in physical and brain functioning alongside symptoms of autism, developmental delay, mental disability, and Alzheimer’s in beings. humans“.
“Likewise, we looked at the potential use of the drug NAP for the treatment of these diseases and found that it is effective against most of these symptoms in laboratory models. This study is an important milestone on the road to the development of a drug, or drugs, that will help children with autism resulting from genetic mutations, as well as Alzheimer’s patients “, concluded the expert.
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