Scientists have discovered a promising drug candidate that seems to normalize the deficiencies of the vocal communication mechanism experienced in the genetic pseudotype.
Activity-dependent neuroprotective protein syndrome (PID) is a rare genetic condition that causes developmental delay, intellectual disability, and autism spectrum disorder symptoms in thousands of children around the world. There is no known remedy for the disorder.
Fortunately, scientists at Tel Aviv University (TAU) have identified a drug candidate – CP201, also known as NAP – that can help improve voice communication skills that are underdeveloped in these patients. The research found that vocal impediments and interrupted neural connectivity in DNAP-deficient mice were normalized after daily injections and intranasal CP201 administrations.
This decisive research was led by Prof. Illana Gozes, Lily and Avraham Gildor Chair for Growth Factor Research and head of the Elton Laboratory of Molecular Neuroendocrinology at TAU Sackler School of Medicine in collaboration with Prof. Anne McKinney of McGill University and its research 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 study research.
PID is caused by truncated mutations of the associated protein, which is essential for brain formation.
Commenting on how this research could positively impact the lives of children with the disease, Prof Gozes, who discovered the PNA gene almost 20 years ago, said: "Children with PADD suffer from intellectual disability, delayed language acquisition and speech.
"Many children are never able to speak.
"We developed a mouse model with DNP deficiency that gave a closer look to the DNP-deficient brain. We found that vocal communication deficits are in fact connected to synaptic pathology and that we can normalize it by injecting the rat model with daily NAP treatments or by administering intranasal doses to the mouse. Gene-specific regulation has improved substantially in most of the parameters we tested, which is great news for the future of PID and autism research. "
Prof.Extensive research into the disease has led to the development of CP201, an important fragment of DNP that protects nerve cells that increases their activity. It increases the plasticity of nerve cells that improves memory and cognition through interaction with terminal binding proteins of the microtubules.
"We saw the positive effects of CP201 on Alzheimer's disease and other neurodegenerative diseases," says Prof.. "We have now discovered that vocal communication impairments in DNP-deficient mice have been successfully normalized.
"CP201 systemic injections or daily intranasal applications in non-breast-fed mice have affected global changes in brain plasticity, substantially improving developmental milestones."
The new study was conducted over two years. The researchers used cognitive behavioral tests and gene expression analysis to evaluate the developmental milestones of 72 DNP-deficient mice. They also applied ultrasonic vocalization analysis on 28 pDNA-deficient mice and compared them with the results of 50 "normal" mice.
Ramot, the technology transfer arm of Tel Aviv University, has licensed the NAP (CP201) for Coronis Neuroscience for development. The US Food and Drug Administration (FDA) has since granted the CP201 Orphan Drug status for the treatment of PID in the United States.
According Prof., the current study paves the way for a clinical trial. "The NAP (CP201) demonstrated the involvement of the brain target and great potential to address the impairments of social, motor and vocal communication in future clinical studies aimed at intellectual disability / autism," she says.
Coronis Neurosciences has just completed a pre-IND (new drug research program) meeting with the FDA with positive results and a roadmap for successful submission of the IND to CP201 in the pDNA syndrome. The IND program is the means by which a pharmaceutical company obtains permission to initiate clinical trials in humans.
The study was published in the Journal of Clinical Investigation.