MAKING STRIDES TO HELP OUR CHILDREN THROUGH RESEARCH FOR TREATMENTS AND CURES
We have an amazing and invested research team, comprised of world-renowned scientists at leading universities and biotech companies working hard to find a treatment and cure for all individuals around the world with ADNP syndrome.
The foundation is funding and collaborating with organizations who are running clinical trials, testing both existing drugs, as well as new state-of-the-art treatments, such as high throughput screening, gene therapies and antisense oligonucleotide therapies.
We also began our quest to build a biorepository and ADNP models (ASSETS) that replicate the ADNP gene mutations that exist in our children. Current models produced at Universities are not easily shared and often come with a licensing agreement and fees that turn off potential researchers and biotech. The ASSETS created by the ADNP Kids Research Foundation will be cataloged and made easily available to quality researchers and biotech companies around the world to work on ADNP drug discovery and development with no restrictions or time consuming road blocks.
The foundation is funding and collaborating with organizations who are running clinical trials, testing both existing drugs, as well as new state-of-the-art treatments, such as high throughput screening, gene therapies and antisense oligonucleotide therapies.
We also began our quest to build a biorepository and ADNP models (ASSETS) that replicate the ADNP gene mutations that exist in our children. Current models produced at Universities are not easily shared and often come with a licensing agreement and fees that turn off potential researchers and biotech. The ASSETS created by the ADNP Kids Research Foundation will be cataloged and made easily available to quality researchers and biotech companies around the world to work on ADNP drug discovery and development with no restrictions or time consuming road blocks.
CURRENT ADNP RESEARCH PROJECTS
DRUG TRIAL:
LOW DOSE KETAMINE FOR ADNP
Our ADNP research program partnership with the Seaver Autism Center at Mount Sinai (SEAVER) team overseen by Dr. Joseph Buxbaum has made huge strides. The most exciting project progress has been made by Dr. Alexander Kolevzon and team who completed the first-ever clinical trial for ADNP syndrome, testing low-dose ketamine as a potential treatment. In this FDA Phase 2A, single dose, open label study, ten children received intravenous ketamine and were monitored over the course of four weeks. Based on preliminary data from clinician-rated assessments and parent reports, they found ketamine to be associated with improvements in social behavior, attention deficit and hyperactivity, restricted and repetitive behaviors, and sensory sensitivities. Their findings are promising and support the continuation of the ketamine drug trial in ADNP syndrome. Next steps include analyses of RNA sequencing, electroencephalography (EEG), eye tracking, and blood-based biomarker.
BIOMARKERS AND OUTCOME MEASURES:
SENSORY REACTIVITY
In clinical research, Dr. Paige Siper and team at SEAVER carried out detailed phenotyping of 22 individuals seen through an ADNP study with ADNP syndrome and published their observations that ADNP is associated with sensory reactivity symptoms, which may represent a therapeutic target.
ELECTROPHYSIOLOGY & EYE TRACKING
Event-related potentials, visual and auditory evoked potentials, and eye tracking tasks have shown distinctive changes to patients with ADNP syndrome. Electrophysiological tasks involve placing non-invasive electrodes on your child’s head. Your child will be asked to look at patterns on computer monitors and listen to different sounds.
DNA METHYLATION
Individuals with ADNP syndrome can be placed in one of two groups, with differing epigenetic signatures (which are reproducible DNA methylation changes).
The preclinical team led by Dr. Ana Kostic at SEAVER has developed genetically engineered and patient-derived stem cells using the blood from our children to identify deficiencies in nerve/brain cell activity due to ADNP mutations. They are examining whether ADNP mutations change the structure and function of nerve cells, compared to control cell lines. Any alterations in nerve cells caused by mutations in ADNP provide a means of identifying pathways and mechanisms that could be targeted pharmacologically to alleviate the symptoms of ADNP syndrome. As part of these studies, they will be evaluating the effect of ketamine and NAP in rescuing the deficits caused by ADNP mutations.
SEAVER in collaboration with Neucyte, they are working to characterize several patient-derived cell lines and hopefully develop additional assays for pharmacological testing.
SEAVER in collaboration with Scripps Institute, that have used a patient-derived cell line to screen a compound library (including thousands of possible small molecule drugs) in a high-throughput assay. They are now in the process of validating initial hits in the assays developed by the preclinical team and are in the process of publishing.
SEAVER in collaboration with Rumi Scientific, they have been able to characterize genetically engineered ADNP-deficient lines in their proprietary brain organoid platform and the next step is to confirm the findings in patient-derived cell lines.
Recently, the mouse model has been developed and sent to SEAVER which includes a clinically relevant mutation. They are now moving forward into characterization. The characterization of the mouse model is proposed to take two to three years. This will allow the team to understand how ADNP mutations impact brain development and function. They will also work with an experienced contract research organization (CRO), to evaluate electrophysiological measures (which are reflective of brain function) in this mouse model.
LOW DOSE KETAMINE FOR ADNP
Our ADNP research program partnership with the Seaver Autism Center at Mount Sinai (SEAVER) team overseen by Dr. Joseph Buxbaum has made huge strides. The most exciting project progress has been made by Dr. Alexander Kolevzon and team who completed the first-ever clinical trial for ADNP syndrome, testing low-dose ketamine as a potential treatment. In this FDA Phase 2A, single dose, open label study, ten children received intravenous ketamine and were monitored over the course of four weeks. Based on preliminary data from clinician-rated assessments and parent reports, they found ketamine to be associated with improvements in social behavior, attention deficit and hyperactivity, restricted and repetitive behaviors, and sensory sensitivities. Their findings are promising and support the continuation of the ketamine drug trial in ADNP syndrome. Next steps include analyses of RNA sequencing, electroencephalography (EEG), eye tracking, and blood-based biomarker.
- $150,000 (FUNDED BY ADNP-KRF) Trial completed August 2021 - Publication due Q4-21
- $43,000 (CONTRACT PENDING - ADNP-KRF)
- Phase 3 drug trial cost unknown (phase 3 estimated up to $2million - ADNP-KRF) Seaver's estimated Start Date Q1-22
BIOMARKERS AND OUTCOME MEASURES:
SENSORY REACTIVITY
In clinical research, Dr. Paige Siper and team at SEAVER carried out detailed phenotyping of 22 individuals seen through an ADNP study with ADNP syndrome and published their observations that ADNP is associated with sensory reactivity symptoms, which may represent a therapeutic target.
ELECTROPHYSIOLOGY & EYE TRACKING
Event-related potentials, visual and auditory evoked potentials, and eye tracking tasks have shown distinctive changes to patients with ADNP syndrome. Electrophysiological tasks involve placing non-invasive electrodes on your child’s head. Your child will be asked to look at patterns on computer monitors and listen to different sounds.
DNA METHYLATION
Individuals with ADNP syndrome can be placed in one of two groups, with differing epigenetic signatures (which are reproducible DNA methylation changes).
The preclinical team led by Dr. Ana Kostic at SEAVER has developed genetically engineered and patient-derived stem cells using the blood from our children to identify deficiencies in nerve/brain cell activity due to ADNP mutations. They are examining whether ADNP mutations change the structure and function of nerve cells, compared to control cell lines. Any alterations in nerve cells caused by mutations in ADNP provide a means of identifying pathways and mechanisms that could be targeted pharmacologically to alleviate the symptoms of ADNP syndrome. As part of these studies, they will be evaluating the effect of ketamine and NAP in rescuing the deficits caused by ADNP mutations.
SEAVER in collaboration with Neucyte, they are working to characterize several patient-derived cell lines and hopefully develop additional assays for pharmacological testing.
- $182,200 (FUNDED BY ADNP-KRF)
- $95,000 (CONTRACT PENDING - ADNP-KRF)
SEAVER in collaboration with Scripps Institute, that have used a patient-derived cell line to screen a compound library (including thousands of possible small molecule drugs) in a high-throughput assay. They are now in the process of validating initial hits in the assays developed by the preclinical team and are in the process of publishing.
SEAVER in collaboration with Rumi Scientific, they have been able to characterize genetically engineered ADNP-deficient lines in their proprietary brain organoid platform and the next step is to confirm the findings in patient-derived cell lines.
Recently, the mouse model has been developed and sent to SEAVER which includes a clinically relevant mutation. They are now moving forward into characterization. The characterization of the mouse model is proposed to take two to three years. This will allow the team to understand how ADNP mutations impact brain development and function. They will also work with an experienced contract research organization (CRO), to evaluate electrophysiological measures (which are reflective of brain function) in this mouse model.
- $400,000 (COST - ADNP-KRF)
- $1,700,000 (COST Seaver to apply for NIH grant for 5 year study)
ADNP GRANT AWARDS & COLLABORATIVE RESEARCH
Our first grant of 2021 was awarded to Dr. Thomas Frazier (CSO of Autism Speaks and Professor of Psychology at John Carrol University). Dr. Frazier is running the Neurobehavioral Evaluation Tool (NET) Study for autism and related genetic syndromes, which will include the participation of ADNP patients and their caregivers in the development and application of the tool. The grant is a joint collaborative effort with several other rare disease organization, primarily funded by PTEN Research, as well as Autism Speaks, SynGAP Research Fund and Malan Syndrome Foundation. The foundation has also connected Dr. Alex Kolevzon of the Seaver Autism Center to the project. His deep clinical expertise with ADNP patients will help inform the work of the NET project. *RECRUTING BEINGS SEPT 2021
Our most recent and very exciting project is FUNCTION at RAREBASE. This is an innovative project involving "15 other similar disease patient organizations" working together on translational therapeutic discovery and development. The project aims to identify candidate drugs and targets based on a combination of high-throughput screening, stem cell biology, and next generation sequencing. The three distinct phases to Function: (1) Prediction Algorithm: Identify candidate drugs or drug targets based on gene expression. (2) Validation Engine: Validate Function drug predictions in patient-derived cell models. (3) Machine Learning: Leverage artificial intelligence and machine learning methods to continually improve prediction algorithms based on data from validation experiments. Initially, Function will screen a library of 2,500+ FDA approved drugs and a proprietary library of drug-like small molecules. In the future, Function will expand to novel compounds that cover a broad range of chemical structures.
- $7,000 (FUNDED BY ADNP-KRF)
- $7,200 (2ND PAYMENT PENDING - ADNP-KRF)
Our most recent and very exciting project is FUNCTION at RAREBASE. This is an innovative project involving "15 other similar disease patient organizations" working together on translational therapeutic discovery and development. The project aims to identify candidate drugs and targets based on a combination of high-throughput screening, stem cell biology, and next generation sequencing. The three distinct phases to Function: (1) Prediction Algorithm: Identify candidate drugs or drug targets based on gene expression. (2) Validation Engine: Validate Function drug predictions in patient-derived cell models. (3) Machine Learning: Leverage artificial intelligence and machine learning methods to continually improve prediction algorithms based on data from validation experiments. Initially, Function will screen a library of 2,500+ FDA approved drugs and a proprietary library of drug-like small molecules. In the future, Function will expand to novel compounds that cover a broad range of chemical structures.
- $150,000 (FUNDED BY ADNP-KRF)
The ADNP Kids Research Foundation has also partnered with CombinedBrain and Coriell Research Institute to create foundation owned “ASSETS” that will be open and easily available to any researcher or industry (biotech/pharma) who wishes to use them to work on future ADNP studies. This is one of our most important projects because we need these ASSETS for current projects already pending, as well as new studies. The ASSETS developed by the ADNP Kids Research Foundation will be made available to researchers around the world, these will not be held for only the US. We are creating these assets to make research easier for scientists around the world; to assist them in moving forward toward our mission of finding treatments and cures as soon as possible.
ADNP INTERNATIONAL PATIENT REGISTRY & NATURAL HISTORY STUDY:
Coming this fall. Currently the Patient Registry is in the IRB approval stage. This registry will allow open access to deidentified information for research and the first ADNP Syndrome Natural History Study which is a critical component of the drug development and trial process.
BIOBANK REPOSITORIES:
Deposit of BLOOD & FIBROBLASTS collected from our children and one sibling (if possible) in progress
CombinedBrain IBX & Coriell NIGMS Human Genetic Cell Repository, sponsored by the National Institute of General Medical Sciences.
ADNP INTERNATIONAL PATIENT REGISTRY & NATURAL HISTORY STUDY:
Coming this fall. Currently the Patient Registry is in the IRB approval stage. This registry will allow open access to deidentified information for research and the first ADNP Syndrome Natural History Study which is a critical component of the drug development and trial process.
- $9,000 (PENDING - FUNDED BY ADNP-KRF)
- $100,000-$300,000 (COST estimate digital N.H.S. - ADNP-KRF)
BIOBANK REPOSITORIES:
Deposit of BLOOD & FIBROBLASTS collected from our children and one sibling (if possible) in progress
CombinedBrain IBX & Coriell NIGMS Human Genetic Cell Repository, sponsored by the National Institute of General Medical Sciences.
- CB/IBX cost unknown
- Coriell NIGMS Repository funded - NIH
DEVELOP and CATALOG ADNP MODEL ASSETS:
Three to six iPSC lines through IBX (in process)Three iPSC lines at Corriell Research InstituteDifferentiated NeuronsOrganoids
Fibroblasts (3 lines) – University of Washington
Deidentified Patient Data: ADNP Patient Registry & Natural History Study
Three to six iPSC lines through IBX (in process)Three iPSC lines at Corriell Research InstituteDifferentiated NeuronsOrganoids
- $ cost unknown
- $40,000 Mouse Build (FUNDED BY ADNP-KRF)
- $300,000-$400,000 Charaterization (COST - ADNP-KRF)
Fibroblasts (3 lines) – University of Washington
Deidentified Patient Data: ADNP Patient Registry & Natural History Study
NEW CUTTING EDGE INVESTIGATIVE THERAPY PROPOSALS
As we build awareness of ADNP Syndrome, researchers are now coming to ADNP Kids Research Foundation with proposals for innovative and impressive therapeutic projects. The projects listed below are ones that the foundation agrees are important and could be very impactful.
ANTISENSE OLIGONUCLEOTIDE BASED THERAPY:
Preliminary investigation of possible ASO therapeutic approach - project and company are CONFIDENTIAL
GENE THERAPY, ASO & CRISPRa-BASED GENE ACTIVATION THERAPY
From the Interventional Genetics team at US Davis
Proposal: Rapid development and evaluation of multiple "best-in-class" gene therapy and "best-in-disease" (CRISPR Cas 9 epigenetic activation) treatments for ADNP syndrome delivered by viral vector, to increase ADNP expression. These approaches, directed by complementary leaders in their fields at both UC Davis and the MIND Institute, proposes the highest likelihood of successful therapeutic development. Proposal is a 3 year project costing approximately $4million dollars including indirect costs (direct costs are below).
ANTISENSE OLIGONUCLEOTIDE BASED THERAPY:
Preliminary investigation of possible ASO therapeutic approach - project and company are CONFIDENTIAL
- $90,000 (Proof of Concept COST - ADNP-KRF)
- $500,000+ (COST Differentiated Neuron Development and Characterization - ADNP-KRF)
GENE THERAPY, ASO & CRISPRa-BASED GENE ACTIVATION THERAPY
From the Interventional Genetics team at US Davis
Proposal: Rapid development and evaluation of multiple "best-in-class" gene therapy and "best-in-disease" (CRISPR Cas 9 epigenetic activation) treatments for ADNP syndrome delivered by viral vector, to increase ADNP expression. These approaches, directed by complementary leaders in their fields at both UC Davis and the MIND Institute, proposes the highest likelihood of successful therapeutic development. Proposal is a 3 year project costing approximately $4million dollars including indirect costs (direct costs are below).
Our research is not possible without the support from families like you and the philanthropy from generous donors to fund our projects. Together we can continue to make strides to increase the quality of life for individuals with ADNP syndrome.
If you would like to support our work on ADNP syndrome, please DONATE here.
If you would like to support our work on ADNP syndrome, please DONATE here.
