Activity-dependent neuroprotective protein syndrome also known as ADNP syndrome is a genetic disorder found rarely in people. It causes a delay in developmental phases of children like intellectual disability and manifestations of autism spectrum disorder. Though it has attacked millions of children all around the world there is no treatment.
One of the recent studies conducted by Tel Aviv University has found out a drug candidate CP201- NAP, which may help to improve the vocal communication abilities that are not properly developed due to this syndrome. As per the research the conditions of vocal disability and disturbed neural connectivity in ADNP syndrome mice improved by the intake of daily injections and intranasal administration of CP201.
The research was carried out by by Prof. Illana Gozes, the Lily and Avraham Gildor Chair for the Investigation of Growth Factors and head of the Elton Laboratory for Molecular Neuroendocrinology at TAU’s Sackler Faculty of Medicine, in collaboration with Prof. Anne McKinney of McGill University and her research group and Dr. Vlasta Korenková of the BIOCEV Institute of Biotechnology.
TAU doctoral students Gal Hacohen-Kleiman, Shlomo Sragovich, Gidon Karmon, Iris Grigg and Dr. Metsada Pasmanik-Chor conducted the research for the study, which was published in the November print issue of the Journal of Clinical Investigation.
Giving ADNP Syndrome Children a Voice
The main cause of ADNP syndrome are the mutations in the ADNP protein which is a critical constituent for brain development.
“Children with ADNP syndrome suffer from an intellectual disability, delayed language acquisition, and speech impediments,” says Prof Gozes’. There are a number of children who fully lose the ability to talk and communicate.
“We developed a mouse model of ADNP deficiency that offered a closer look at the ADNP-deficient brain. We discovered that vocal communication deficiencies are in fact connected to synaptic pathology and that we could normalize this by injecting the mouse model with daily NAP treatments or administering intranasal doses to the mouse. Specific gene regulation substantially improved on most of the parameters that we tested, which is great news for the future of ADNP and autism research.”
Nearly 20 years ago Professor Gozes’ identified the ADNP gene which led to the development of CP201, an important constituent to protect the nerve cells of ADNP. It plays its role in boosting the memory and cognition by increasing the nerve cell plasticity.
“We have seen CP201’s positive effects in Alzheimer’s and other neurodegenerative diseases,” says Prof. Gozes. “We have now found that vocal communication impediments in ADNP-deficient mice were successfully normalized. The CP201 systemic injections or intranasal daily applications in nonsuckling mice affected global changes in brain plasticity, substantially improving developmental milestones.”
This 2-year long research used 150 mice and cognitive behavioral test and gene expression analysis to study the developmental hinderances in the 72 ADNP-deficient mice. The other 28 ADNP-deficient mice were exposed to ultrasonic vocalization analysis, the results were compared with the rest of 50 normal mice.
A Promising Candidate for Clinical Trials
The U.S. FDA has approved the CP201 Orphan Drug status for treating the conditions like ADNP syndrome. According to Professor Gozes, this research has paved a path for the other researchers to conduct a clinical trial.
“NAP (CP201) has demonstrated brain target engagement and great potential for treating social, motor and vocal communication impediments in future intellectual disabilities/autism-oriented clinical trials,” she says.