Tech Portfolio

Principal researcher name: Dr Hagit Friedman

Invention area: life science & Pharma

Background:
Prematurity, a continuously growing phenomenon is a risk factor for multisystem injury, as body systems of the premature infants are not ripe for life out of uterus. Health problems may include immediate and long term complications, and in the long term, prematurity leads to high risk for brain injury and developmental impairments, ranging from Minor Neurological Dysfunction, through ASD, to Cerebral Palsy. With infants at risk, early detection and intervention for developmental impairments is crucial.

A young infant's cry is usually a signal of hunger, pain, or discomfort. But fine sound components of an infant cry, including those which are hardly noticeable to the human ear, can hold important information about the infant’s health and neural development. Various conditions might be reflected in vocal characteristics, including birth trauma, or brain injury. One famous extreme disorder is "cry of the cat" syndrome (caused by a genetic anomaly), but fine differences in infant's cry may also be indicators of an infant’s health. Today, Markers of neural development can be observed and quantified in the newborn and young infant examining the quality of spontaneous movements and oral neuromotor competence. Hence, if neurological deficits change the way infants activate their pharynx and vocal system, then even tiny differences might manifest themselves in differences in vocal characteristics. Vocal analysis may be a nonintrusive way to identify and quantify neurodevelopment impairments
in very young premature infants, and together with analysis of the quality of spontaneous movements and oral neuromotor competence, make a better and more reliable diagnostic tool.
Dr Friedman aims in this project are to analyze infants' vocal characteristics using a computer based tool and to define the correlation between infant's vocal characteristics and infant early development, Reflected in and the quality of infant's feeding movements and general movements.
The study is designed parallel prospectively (with young premature neonates) and retrospectively (vocal analysis of existing data, and speech and developmental outcome of these toddlers).

Usage:
Early assessment and detection of developmental impairments is crucial for early and effective intervention as early identification will support initiation of early treatment and may minimize neurological and functional deficits

Researcher : Dr. Inna Gaisler-Salomon

Background

Schizophrenia is a severe mental disorder that is characterized by debilitating symptoms of impaired perception, cognition, speech, affect and behavior. According to the National Institute of Mental Health (NIMH), the prevalence of schizophrenia is approximately 1.1% of the population over the age of 18. This means that as many as 51 million people worldwide suffer from schizophrenia today.

Despite its prevalence, the etiology of this disorder remains largely unclear, and therefore effective long-term cures or prevention have not yet been discovered. Existing medication prescribed for people with schizophrenia has significant side effects and can only treat some of the symptoms.

Novel Animal Models and Targets for Pharmaceutical Testing

Research conducted by Dr. Inna Gaisler-Salomon, head of the Molecular Basis for Psychopathology Lab in the University of Haifa’s Department of Psychology, aims at developing animal models using a combination of genetic, molecular and behavior tools to address questions related to the etiology, symptomatology and treatment of schizophrenia.

Glutamate abnormalities have been extensively reported in schizophrenia, but the precise nature and directionality of these abnormalities has remained unresolved. Along with her research team, Dr. Gaisler-Salomon is focusing research on glutamate synthesis and transmission using novel animal models that they are developing, and enabling the discovery of targets for developing novel drugs to treat schizophrenia.

Research Status
The research team examines mice that are genetically modified to express abnormal levels of proteins involved in glutamate metabolism, observing not only the effects of these manipulations on susceptibility, but also on resilience to schizophrenia.

Using genetic and molecular techniques (genetically modified mice, viral-induced manipulations, chemogenetics), the researchers are able to manipulate glutamate levels in a spatially and temporally limited manner. Baseline and drug-induced behavioral flexibility and attentional cognitive shifting is then tested using novel behavioral assays developed and optimized in the Gaisler-Salomon Lab. Their findings are leading to a better understanding of schizophrenia etiology and are likely to present new treatment venues for its symptoms.

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Related pages

Inna Gaisler- Salomon, Dr. - Researcher page

The Molecular Basis for Psychopathology Lab

Researcher: Prof. Kobi Rosenblum 

Co-researchers: Dr. Iliana Barrera, Dr. Shunit Ben Ari

Background

Alzheimer's Disease is one of the most common forms of dementia. It is generally diagnosed in people over the age of 65 years, although early onset is possible. It is a progressive and terminal disease, for which there is currently no cure.

The ability to form new and stable memories deteriorates with age and is a clear hallmark of different neurodegenerative diseases, including Alzheimer's Disease (AD) and frontotemporal dementia. The vast majority of AD cases have complex etiology with multiple genetic and environmental factors influencing the development of the disease. Indeed, different animal models are used to study the complex biology underlying AD.

Alzheimer's Disease International has stated that in 2015 some 47 million people worldwide were living with Alzheimer's or related dementia and this number is expected to reach 131.5 million in 2050. The organization notes that Alzheimer’s and other dementias are the top cause of disabilities in later life.

Drug Development for Improving Cognitive Impairment

Studies have shown that phosphorylation levels of a protein known as PKR are elevated in Alzheimer's Disease. Prof. Kobi Rosenblum, Head of the University of Haifa's Laboratory for Research of Molecular and Cellular Mechanisms Underlying Learning and Memory, is working towards the development of a memory-enhancing drug that is based on manipulation of the PKR protein in order to help combat the devastating memory loss and other cognitive abilities that affect people with AD and mild cognitive impairment.

Research Status
Earlier studies have shown that protein synthesis is connected to creating memory in the brain. Rapid production of proteins leads to stronger and long-term memory capabilities, while slower protein production results in weaker memory that does not consolidate into long-term memory and leads to memory loss.

Prof. Rosenblum and his research team have managed to maneuver the activity of the PKR protein molecule, without harming normal brain functioning. The team have been able to inhibit PKR activity in laboratory rats, resulting in a 30% improvement of memory.

This research is establishing an opportunity to develop medications that can improve cognitive functioning, slowing the progress of AD and other forms of dementia.

IP Status
US patent granted – Improving cognitive function (8334262 B2)

Market potential 
Carmel established a company, MemoFit [link to company page] to advance and commercialize this technology, with a seed investment from the Carmel Innovations Fund and other partners. It is now a portfolio company at FutuRx biotech incubator and renamed Protekt Therapeutics Ltd.

Investment & partnership opportunities 

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Protekt Therapeutics Ltd.

Kobi Rosenblum, Prof. - Researcher page

Researcher: Dr. Orly Rubinsten

Background

Generalized Anxiety Disorder (GAD) is a prevalent disorder, characterized by persistent worrying, physical symptoms, and tension. Current treatments, drug therapies (e.g., selective serotonin reuptake inhibitors, SSRI) and cognitive behavioral therapy (CBT), each have drawbacks. Two novel treatments, Attention Bias Modification Treatment (ABMT) and neurofeedback (NF), show promise, but have yielded inconsistent results. ABMT is a cognitive treatment aimed at helping patients shift their attention away from threat stimuli. NF is an implicit training of brain function via real-time feedback, based on neural signals while watching a movie or hearing music, which treats the faulty brain activity associated with conditions such as anxiety. To date no effective long-term cure or prevention has been found for the disease.

According to the Anxiety and Depression Association of America, GAD affects 6.8 million adults, or 3.1% of the U.S. population, in any given year. Women are twice as likely to be affected by the disorder, which develops gradually, most commonly between childhood and middle age.

Novel and Effective Clinical Practice for GAD treatment

Dr. Orly Rubinstein, head of the University of Haifa’s Language and Numbers Laboratory, is introducing a novel approach in clinical practice to treat GAD, using machine-learning algorithms in combination with cognitive psychology and neurophysiological methods.

By implementing ABMT to modify threat-related attention bias in anxiety and simultaneously providing visual neurofeedback, the participant is encouraged to counter deficient brain patterns. This novel neurocognitive treatment (NCT) will thereby enable performance of cognitive tasks while receiving neurofeedback.

The NCT is based on principals of machine learning (ML), a method of data analysis that promotes quick and accurate understanding of big data leading to predications for future data, and brain-computer interface (BCI), that acquires and analyzes brain signals to create a high-bandwidth communication channel in real time between the human brain and the computer.

Research Status
Dr. Rubinsten’s NCT paradigm is being carefully designed, by systematically manipulating critical parameters such as mental task content, feedback type, training duration, etc. Machine-learning principals are being applied to recognize individual behavior and brain patterns and the supervised learning algorithm will provide real-time feedback.

The research team expects this to method to allow the participant to achieve the behavioral and neural goals that they set. The NCT will be the first step in the development of a platform that will consist of various cognitive tasks combined with NF protocols.

Since no currently existing product enables performance of cognitive tasks while receiving NF, employing both treatments simultaneously has potential scientific, therapeutic and commercial value. NCT will potentially enable both clinicians and scientists to use any cognitive task under NF, potentially opening the doors for future treatments for many mental disorders, all under the frame of personalized medicine. BCI could also help with diagnosis as classification algorithms will be applied. This platform will be the first NF treatment to implement co-adaptation, where machine and patient adapt to one another.

IP Status
US Provisional Patent Application ̶ System and method for treatment of mental disorder

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Main Researcher : Prof. Gal Richter-Levin 

 Background

Psychiatric disorders such as depression, anxiety and schizophrenia are leading causes of disability worldwide, and have a huge social impact. Available drugs prescribed to treat these disorders are mostly non-specific and help, in the best cases, 40-50% of patients. All cause side effects, and many of the existing drugs (some of which have become blockbusters) are coming close to patent expiration.

Despite the clear need for better drugs and major advances in the understanding of the molecular basis of these disorders in recent years, efforts to discover and develop new drugs for neuropsychiatric disorders have been relatively unsuccessful.

The development of new drugs is hampered by the absence of adequate predictive animal models for preclinical drug screening. Inadequate animal models have led to continuous failure in identifying relevant novel candidates for drug development and to missing identifying relevant properties of candidate drugs, which, as a result, were not further tested.
Preclinical screening, at the earliest stages of discovery, and valid animal models for early compound selection are mandatory to provide initial assessment of the functional effects of novel compounds in drug development.

Advancing Preclinical Screening and Animal Models

Of all the major psychiatric indications, the depression and anxiety markets represent and continue to represent the highest levels of unmet need.

The University of Haifa's Brain and Behavior Laboratory headed by Prof. Gal Richter-Levin has developed novel, predictive preclinical models and more reliable complex screening methodologies which overcome shortcoming of previous animal models. These advanced tools are offered to pharmaceutical companies in the field both as drug-screening platforms that are able to reliably identify properties of drugs relevant to human symptomology, and as an effective platform for identifying relevant novel candidates.

According to a market research report by BBC Research, the global market for drugs used to treat mental disorders was valued at $70.1 billion in 2012 and is estimated to have declined slightly to nearly $69 billion in 2013.

The Brain and Behavior Laboratory Services

• Established novel and unique behavioral animal models for anxiety, post-traumatic stress disorder and depression.
- For effective drug screening
- For identifying novel candidates for drug development
• A multidisciplinary approach for designing the preclinical models suitable to the most relevant symptoms of a specific disorder, including classical electrophysiological parameters, behavioral parameters and unique data analysis methods.
• Biochemical and electrophysiological measurements and analysis power.
• A committed scientific team with the relevant experience and expertise to develop and set up relevant rodent models.

Investment & partnership opportunities

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Gal Richter - Levin, Prof.

Pharma/Drug Delivery

Developing a first-in-class drug candidate to prevent debilitating consequences of fear-related diseases such as posttraumatic stress disorder (PTSD).

Researchers: Prof. Rafi Lamprecht, Dr. Monica Dines

Background

The human brain develops fear memory to help adapt behavior and avoid danger in potential future fearful events. When fear memory becomes disproportionate to cope with stimulus or is invoked in inappropriate situations, an individual develops fear-related disorders, such as post-traumatic stress disorder (PTSD).

Based on fear-memory triggers, PTSD patients may experience flashbacks, distressing dreams, mentally re-experiencing the event, or intense negative psychological or physiological responses to stimuli recalling it.

According to the National Center for PTSD in USA about 7 out of every 100 people will experience PTSD at some point in their lives. These individuals experience excessive and debilitating fear that significantly impairs their ability to maintain a normal life.

Drug Development for Inhibition of Harmful Fear Memory
Prof. Rafi Lamprecht and Dr. Monica Dines from the University of Haifa are in the advanced stages of developing and evaluating a drug for the treatment of fear and stress-related disorders, aimed at reducing or preventing the debilitating consequences of fearful memories. The drug, pep-EphrinA4, is intended to inhibit the development of fear memory following traumatic event.

Research Status
The researchers have achieved excellent preliminary results with pep-EphrinA4, showing the effectiveness of this drug in impairing the formation of long-term fear memory in a useful animal model. Results show that the drug is specific, impairs fear memory formation in amygdala and importantly impairs the formation of long-term fear memory when subcutaneously injected acutely and systemically one hour after fear conditioning.

Pep-EphrinA4 has the potential to serve as a first-in-class PTSD drug candidate to prevent some of the debilitating consequences of fear-related diseases such as PTSD.

Investment & partnership opportunities
Carmel established MemoDero Ltd to advance and commercialize this technology, with a seed investment from the Carmel Innovations Fund.

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Rafi Lamprecht, Dr.- Researcher page

Researcher: Prof. Edi Barkai       

Discovering a new drug treatment approach to inhibit the onset of dementia.

Background : Dementia, most commonly Alzheimer’s disease, is a devastating chronic brain condition that disrupts thinking, orientation, behavior, and memory processes. Individuals suffering from dementia are faced with challenges performing everyday activities and engaging in social interaction. As the condition deteriorates, functional dependence on family, caregivers and society increases.
To date no effective long-term cure or prevention has been found for the disease.
According to a World Health Organization report, dementia is affecting some 47 million people worldwide. This number is likely to increase with 9.9 million new cases every year, the report states, making it one of the world’s greatest health challenges.   

Dementia is normally preceded by a period of mild cognitive impairments (MCI). Studies have shown a positive link between higher education and lower prevalence of MCI, indicating that the learning process has a protective role. 

Prof. Edi Barkai of the University of Haifa’s Sagol Department of Neurobiology and Head of the Laboratory for Neurobiology of Learning and Memory is on the path to developing a cognitive/learning-enhancing drug that could counter cognitive deficits suffered by dementia patients. 

 
Research Status :

Barkai’s research has identified a specific receptor in the brain, of the mGluR family, that inhibits learning when its excitability is blocked and improves learning when excitability is consistently enhanced. Using a research compound which activates this receptor, Prof. Barkai’s group has successfully shown that learning is significantly enhanced in a validated animal model of learning.
The compound is currently being modified and tested to develop a drug that will serve as a potent cognitive enhancer to tackle the onset of dementia and other cognitive deficits.
A pioneer approach developing a drug candidate to prevent the devastating deterioration of cognitive functioning associated with dementia. 

Market potential

Carmel established MemoBoost Ltd  to advance and commercialize this technology, with a seed investment from the Carmel Innovations Fund.

Investment & partnership opportunities 

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Related pages

Prof. Barkai researcher page

MemoBoost Ltd.