Kleefstra Syndrome Drug Development Research Fund

We want to begin our quarterly update by once again expressing our gratitude for your continued support in our efforts to advance drug treatments for those impacted by Kleefstra Syndrome. Our progress to date would not be possible without you. To learn more, see below for an update on our efforts that past GlobalGiving donations have supported thus far.

Research Project: Screening Potential Drugs To Upregulate EHMT1 (Kleefstra Syndrome Gene)

The aim is to develop an assay for screening chemical compounds/drugs, specifically looking for those that increase the production of the EHMT1 protein (which is insufficiently produced in Kleefstra Syndrome patients). Why might this overall approach work? Like all humans, Kleefstra Syndrome patients are supposed to have two healthy copies of EHMT1. However, these patients' gene mutations or deletions result in one copy being deficient. In identifying drugs that can successfully interact with and stimulate increased production of EHMT1, we may be able to produce enough of the protein to compensate for the deficiency. This approach is known as “upregulation” and has proven successful in other diseases with similar challenges. Once our assay is finalized, we plan to screen approximately 9,000 thousand compounds/drugs, including the vast majority of FDA-approved drugs; FDA-approved drugs have already passed many hurdles and early success with such drugs may result in tremendous time and cost savings. This project continues to be a high priority, with an expected completion now around mid-2020. The goal of the project remains identifying a potential drug candidate for testing on human Kleefstra Syndrome patients.

We want to begin our quarterly update by once again expressing our gratitude for your continued support in our efforts to advance drug treatments for those impacted by Kleefstra Syndrome. Our progress to date would not be possible without you. To learn more, see below for an update on our efforts that past GlobalGiving donations have supported thus far.

Research Project: Screening Potential Drugs To Upregulate EHMT1 (Kleefstra Syndrome Gene)

The aim is to develop an assay for screening chemical compounds/drugs, specifically looking for those that increase the production of the EHMT1 protein (which is insufficiently produced in Kleefstra Syndrome patients). Why might this overall approach work? Like all humans, Kleefstra Syndrome patients are supposed to have two healthy copies of EHMT1. However, these patients’ gene mutations or deletions result in one copy being deficient. In identifying drugs that can successfully interact with and stimulate increased production of EHMT1, we may be able to produce enough of the protein to compensate for the deficiency. This approach is known as “upregulation” and has proven successful in other diseases with similar challenges. Once our assay is finalized, we plan to screen thousands of compounds/drugs, including many of the FDA-approved drugs; FDA-approved drugs have already passed many hurdles and early success with such drugs may result in tremendous time and cost savings. This project continues to be a high priority, with important screening data continued to be expected in late 2019 / early 2020. The goal of the project remains identifying a potential drug candidate for testing on human Kleefstra Syndrome patients.

We want to begin our quarterly update by once again expressing our gratitude for your continued support in our efforts to advance drug treatments for those impacted by Kleefstra Syndrome. Our progress to date would not be possible without you. To learn more, see below for an update on our efforts that past GlobalGiving donations have supported thus far.

Research Project: Screening Potential Drugs To Upregulate EHMT1 (Kleefstra Syndrome Gene)

The aim is to develop an assay for screening chemical compounds/drugs, specifically looking for those that increase the production of the EHMT1 protein (which is insufficiently produced in Kleefstra Syndrome patients). Why might this overall approach work? Like all humans, Kleefstra Syndrome patients are supposed to have two healthy copies of EHMT1. However, these patients’ gene mutations or deletions result in one copy being deficient. In identifying drugs that can successfully interact with and stimulate increased production of EHMT1, we may be able to produce enough of the protein to compensate for the deficiency. This approach is known as “upregulation” and has proven successful in other diseases with similar challenges. Once our assay is finalized, we plan to screen thousands of compounds/drugs, including many of the FDA-approved drugs; FDA-approved drugs have already passed many hurdles and early success with such drugs may result in tremendous time and cost savings. This project continues to be a high priority, with important screening data continued to be expected in late 2019. The goal of the project remains identifying a potential drug candidate for testing on human Kleefstra Syndrome patients.

We want to begin our quarterly update by once again expressing our gratitude for your continued support in our efforts to advance drug treatments for those impacted by Kleefstra Syndrome. Our progress to date would not be possible without you. To learn more, see below for an update on our efforts that past GlobalGiving donations have supported thus far.

Research Project: Screening Potential Drugs To Upregulate EHMT1 (Kleefstra Syndrome Gene)

The aim is to develop an assay for screening chemical compounds/drugs, specifically looking for those that increase the production of the EHMT1 protein (which is insufficiently produced in Kleefstra Syndrome patients). Why might this overall approach work? Like all humans, Kleefstra Syndrome patients are supposed to have two healthy copies of EHMT1. However, these patients’ gene mutations or deletions result in one copy being deficient. In identifying drugs that can successfully interact with and stimulate increased production of EHMT1, we may be able to produce enough of the protein to compensate for the deficiency. This approach is known as “upregulation” and has proven successful in other diseases with similar challenges. Once our assay is finalized, we plan to screen thousands of compounds/drugs, including many of the FDA-approved drugs; FDA-approved drugs have already passed many hurdles and early success with such drugs may result in tremendous time and cost savings. This project continues to be a high priority, with important screening data now expected within the 2019 calendar year. The goal of the project remains identifying a potential drug candidate for testing on human Kleefstra Syndrome patients.

We want to begin our quarterly update by once again expressing our gratitude for your continued support in our efforts to advance drug treatments for those impacted by Kleefstra Syndrome. Our progress to date would not be possible without you. To learn more, see below for an update on our efforts that past GlobalGiving donations have supported thus far.

Research Project: Screening Potential Drugs To Upregulate EHMT1 (Kleefstra Syndrome Gene)

The aim is to develop a screening tool or assay for chemical compounds/drugs, specifically looking for those that increase the production of the EHMT1 protein (which is insufficiently produced in Kleefstra Syndrome patients). Why might this overall approach work? Like all humans, Kleefstra Syndrome patients are supposed to have two healthy copies of EHMT1. However, these patients’ gene mutations or deletions result in one copy being deficient. In identifying drugs that can successfully interact with and stimulate increased production of EHMT1, we may be able to produce enough of the protein to compensate for the deficiency. This approach is known as “upregulation” and has proven successful in other diseases with similar challenges. Once our tool or assay is developed, we will begin by screening FDA-approved drugs, given these drugs have already passed many hurdles and early success may result in tremendous time and cost savings. This project continues to be a high priority, with important screening data now expected within the 2019 calendar year. The goal of the project remains identifying a potential drug candidate for testing on human Kleefstra Syndrome patients.

We want to begin our quarterly update with some important news. GeneSpark has officially changed its name and is now known as K.I.D.S. IQ Project. Kids with Intellectual Disability Syndromes (K.I.D.S.) such as Kleefstra Syndrome itself, have always been our core focus and we are excited to update our brand to highlight this with our global community and corporate partners. The chosen name continues to reflect our commitment to creating a better future for so many children around the world. Going forward, you will see this brand change reflected throughout our organization, including our website, email and social media. We appreciate your patience and understanding during this transition period. You can now contact us at info@kidsIQproject.org or visit us at www.kidsIQproject.org. If you've been a supporter of ours on social media or other channels, we kindly ask that any references to our organization now reflect the new name and online location. As with everything we do, this change is about taking care of our community and we hope this new name will resonate with you. Our mission and focus remain the same and we are as excited as ever to continue building a strong, impactful and engaging organization to pursue our important goals.

With respect to our research efforts, we would like to once again thank you for your continued support in our efforts to advance drug treatments for those impacted by Kleefstra Syndrome and other Intellectual Disability syndromes. Our progress to date would not be possible without you. To learn more, see below for an update on our efforts that past GlobalGiving donations have supported thus far.

Research Project: Screening Potential Drugs To Upregulate EHMT1 (Kleefstra Syndrome Gene)

The aim is to develop a screening tool for chemical compounds, specifically looking for drugs that increase the production of the EHMT1 protein (which is insufficiently produced in Kleefstra Syndrome patients). Why might this overall approach work? Like all humans, Kleefstra Syndrome patients are supposed to have two healthy copies of EHMT1. However, these patients’ gene mutations or deletions result in one copy being deficient. In identifying drugs that can successfully interact with, and stimulate increased production of EHMT1, we may be able to produce enough of the protein to compensate for the deficiency. This approach is known as “upregulation” and has proven successful in other diseases with similar challenges. Once our tool is developed, we will begin by screening FDA-approved drugs, given these drugs have already passed many hurdles and early success may result in tremendous time and cost savings. This project continues to advance and is still expected to generate important screening data within the 2018 calendar year. The goal of the project remains identifying a potential drug candidate for testing on human Kleefstra Syndrome patients.

GeneSpark would like to once again thank you for your support in our efforts to advance drug research and treatments for those impacted by Kleefstra Syndrome and other Intellectual Disability disorders. Our progress to date would not be possible without you. To learn more, a link to our 2017 Annual Report can be found below. Additionally, we wanted to update you on our efforts that past GlobalGiving donations have supported thus far - see below.

Research Project: Screening Potential Drugs To Upregulate EHMT1 (Kleefstra Syndrome Gene)

The aim is to develop a screening tool for chemical compounds, specifically looking for drugs that increase the production of the EHMT1 protein (which is insufficiently produced in Kleefstra Syndrome patients). Why might this overall approach work? Like all humans, Kleefstra Syndrome patients are supposed to have two healthy copies of EHMT1. However, these patients’ gene mutations or deletions result in one copy being deficient. In identifying drugs that can successfully interact with, and stimulate increased production of EHMT1, we may be able to produce enough of the protein to compensate for the deficiency. This approach is known as “upregulation” and has proven successful in other diseases with similar challenges. Once our tool is developed, we will begin by screening FDA-approved drugs, given these drugs have already passed many hurdles and early success may result in tremendous time and cost savings. This project is advancing and is expected to generate important screening data within the 2018 calendar year. The goal of the project remains identifying a potential drug candidate for testing on human Kleefstra Syndrome patients.

GeneSpark is continuing to fund three research projects and areas, all approved by our Scientific Advisory Board and described in detail below. Our progress to date would not be possible without our donors. All funds raised specifically through GlobalGiving Foundation have been applied to a portion of the funding requirement for the second project described below. Once again, we thank you for your continued support!

Project 1: Kleefstra Syndrome - Focused Drug Screen on Human iPSC-Derived Neurons and Subsequent Mouse Testing of Lead Compounds

Our first project formally began in December 2016 and is being led by Dr. Hans van Bokhoven and Dr. Nael Nadif Kasri, both of Radboud University (The Netherlands), in collaboration with Dr. Hans Bjornsson of Johns Hopkins University in the United States. The leaders of this research team have completed a screen of a short list of chemical compounds (drugs). They leveraged drugs that have historically been able to target syndromes and diseases which are similar to Kleefstra Syndrome, and other drugs well-suited to address the biology of Kleefstra Syndrome itself. How exactly did this screen work? The Radboud team had previously developed Kleefstra Syndrome neurons (brain cells), derived from a patient’s skin sample, through an innovative process involving induced pluripotent stem cell (iPSC) technology. These neurons resided in a petri dish and were evaluated for deficiencies as compared to neurons from a healthy patient. The team began testing the impact of the selected chemical compounds to assess their ability to improve noted deficiencies. After the initial screen of the compounds, the team identified one particular compound which showed significant promise in improving neuronal deficiencies. To our knowledge, this is the first time in history that a specific compound has been shown to improve or reverse Kleefstra Syndrome in a lab environment, in any kind of human or animal model. However, it is important to keep in mind that drug development is a complex and involved process, and this progress requires significant follow-up testing and validation over a multi-year period. The first stages of this testing and validation work has begun and we will continue to provide material milestone updates as they become available. Ultimately, the research team will look to advance a compound to mouse testing in order to better understand behavioural and cognitive impacts. The goal of the project remains identifying a potential drug candidate for testing on human Kleefstra Syndrome patients.

Project 2: Screening Potential Drugs To Upregulate EHMT1 (Kleefstra Syndrome Gene)

Our second project is also underway. The aim is to develop a screening tool for chemical compounds, specifically looking for drugs that increase the production of the EHMT1 protein (which is insufficiently produced in Kleefstra Syndrome patients). Why might this overall approach work? Like all humans, Kleefstra Syndrome patients are supposed to have two healthy copies of EHMT1. However, these patients’ gene mutations or deletions result in one copy being deficient. In identifying drugs that can successfully interact with, and stimulate increased production of EHMT1, we may be able to produce enough of the protein to compensate for the deficiency. This approach is known as “upregulation” and has proven successful in other diseases with similar challenges. Once our tool is developed, we will begin by screening FDA-approved drugs, given these drugs have already passed many hurdles and early success may result in tremendous time and cost savings. This project is in its early phases, but is expected to generate important screening data within the 2018 calendar year. The goal of the project remains identifying a potential drug candidate for testing on human Kleefstra Syndrome patients.

Project 3: Kleefstra Syndrome: Broad-Based Drug Screen on Human iPSC-derived Neurons

Our third project involves developing and converting iPS cells to neuronal cells for detailed study. The neuronal cells (and their associated phenotype) will then be used in a broad-based drug screen covering hundreds of thousands of existing drugs and other non-commercialized compounds. This project is getting ready to enter phase two, which begins with developing neuronal cells for detailed study. The project is expected to generate important screening data within the next 18 months, with a goal of identifying a potential drug candidate for testing on human Kleefstra Syndrome patients.

GeneSpark is continuing to fund three research projects and areas, all approved by our Scientific Advisory Board and described in detail below. Our progress to date would not be possible without our donors. All funds raised specifically through GlobalGiving Foundation have been applied to a portion of the funding requirement for the second project described below. Once again, we thank you for your continued support!

Project 1: Kleefstra Syndrome - Focused Drug Screen on Human iPSC-Derived Neurons and Subsequent Mouse Testing of Lead Compounds

Our first project formally began in December 2016 and is being led by Dr. Hans van Bokhoven and Dr. Nael Nadif Kasri, both of Radboud University (The Netherlands), in collaboration with Dr. Hans Bjornsson of Johns Hopkins University in the United States. The leaders of this research team have completed a screen of a short list of chemical compounds (drugs). They leveraged drugs that have historically been able to target syndromes and diseases which are similar to Kleefstra Syndrome, and other drugs well-suited to address the biology of Kleefstra Syndrome itself. How exactly did this screen work? The Radboud team had previously developed Kleefstra Syndrome neurons (brain cells), derived from a patient’s skin sample, through an innovative process involving induced pluripotent stem cell (iPSC) technology. These neurons resided in a petri dish and were evaluated for deficiencies as compared to neurons from a healthy patient. The team began testing the impact of the selected chemical compounds to assess their ability to improve noted deficiencies. After the initial screen of the compounds, the team identified one particular compound which showed significant promise in improving neuronal deficiencies. To our knowledge, this is the first time in history that a specific compound has been shown to improve or reverse Kleefstra Syndrome in a lab environment, in any kind of human or animal model. However, it is important to keep in mind that drug development is a complex and involved process, and this progress requires significant follow-up testing and validation over a multi-year period. The first stages of this testing and validation work has begun and we will continue to provide material milestone updates as they become available. Ultimately, the research team will look to advance a compound to mouse testing in order to better understand behavioural and cognitive impacts. The goal of the project remains identifying a potential drug candidate for testing on human Kleefstra Syndrome patients.

Project 2: Screening Potential Drugs To Upregulate EHMT1 (Kleefstra Syndrome Gene)

Our second project is also underway. The aim is to develop a screening tool for chemical compounds, specifically looking for drugs that increase the production of the EHMT1 protein (which is insufficiently produced in Kleefstra Syndrome patients). Why might this overall approach work? Like all humans, Kleefstra Syndrome patients are supposed to have two healthy copies of EHMT1. However, these patients’ gene mutations or deletions result in one copy being deficient. In identifying drugs that can successfully interact with, and stimulate increased production of EHMT1, we may be able to produce enough of the protein to compensate for the deficiency. This approach is known as “upregulation” and has proven successful in other diseases with similar challenges. Once our tool is developed, we will begin by screening FDA-approved drugs, given these drugs have already passed many hurdles and early success may result in tremendous time and cost savings. This project is in its early phases, but is expected to generate important screening data within the next 12 months. The goal of the project remains identifying a potential drug candidate for testing on human Kleefstra Syndrome patients.

Project 3: Kleefstra Syndrome: Broad-Based Drug Screen on Human iPSC-derived Neurons

Our third project involves developing and converting iPS cells to neuronal cells for detailed study. The neuronal cells (and their associated phenotype) will then be used in a broad-based drug screen covering hundreds of thousands of existing drugs and other non-commercialized compounds. This project is getting ready to enter phase two, which begins with developing neuronal cells for detailed study. The project is expected to generate important screening data within the next 12 months, with a goal of identifying a potential drug candidate for testing on human Kleefstra Syndrome patients.

GeneSpark is continuing to fund three research projects and areas, all approved by our Scientific Advisory Board and described in detail below. Our progress to date would not be possible without our donors. All funds raised specifically through GlobalGiving Foundation have been applied to a portion of the funding requirement for the second project described below. Once again, we thank you for your continued support!

Project 1: Kleefstra Syndrome - Focused Drug Screen on Human iPSC-derived Neurons and Subsequent Mouse Testing of Lead Compounds

Our first project formally began in December 2016 and is being led by Dr. Hans van Bokhoven and Dr. Nael Nadif Kasri, both of Radboud University (The Netherlands), in collaboration with Dr. Hans Bjornsson of Johns Hopkins University in the United States. The leaders of this research team have completed a screen of a short list of chemical compounds (drugs). They leveraged drugs that have historically been able to target syndromes and diseases which are similar to Kleefstra Syndrome, and other drugs well-suited to address the biology of Kleefstra Syndrome itself. How exactly did this screen work? The Radboud team had previously developed Kleefstra Syndrome neurons (brain cells), derived from a patient’s skin sample, through an innovative process involving induced pluripotent stem cell (iPSC) technology. These neurons resided in a petri dish and were evaluated for deficiencies as compared to neurons from a healthy patient. The team began testing the impact of the selected chemical compounds to assess their ability to improve noted deficiencies. After the initial screen of the compounds, the team identified one particular compound which showed significant promise in improving neuronal deficiencies. To our knowledge, this is the first time in history that a specific compound has been shown to improve or reverse Kleefstra Syndrome in a lab environment, in any kind of human or animal model. However, it is important to keep in mind that drug development is a complex and involved process, and this progress will require significant follow-up testing and validation over a multi-year period. Our Scientific Advisory Board has now approved the first stages of this testing and validation and such work has begun. Ultimately, the research team will look to advance a compound to mouse testing in order to better understand behavioural and cognitive impacts. The goal of the project remains identifying a potential drug candidate for testing on human Kleefstra Syndrome patients.

Project 2: Screening Potential Drugs To Upregulate EHMT1 (Kleefstra Syndrome Gene)

Our second project is also underway. The aim is to develop a screening tool for chemical compounds, specifically looking for drugs that increase the production of the EHMT1 protein (which is insufficiently produced in Kleefstra Syndrome patients). Why might this overall approach work? Like all humans, Kleefstra Syndrome patients are supposed to have two healthy copies of EHMT1. However, these patients’ gene mutations or deletions result in one copy being deficient. In identifying drugs that can successfully interact with, and stimulate increased production of EHMT1, we may be able to produce enough of the protein to compensate for the deficiency. This approach is known as “upregulation” and has proven successful in other diseases with similar challenges. Once our tool is developed, we will begin by screening FDA-approved drugs, given these drugs have already passed many hurdles any early success may result in tremendous time and cost savings. This project is in its early phases and is expected to last up to two years or more from launch. The goal of the project remains identifying a potential drug candidate for testing on human Kleefstra Syndrome patients.

Project 3: Kleefstra Syndrome: Broad-Based Drug Screen on Human iPSC-derived Neurons

Our third project involves developing and converting iPS cells to neuronal cells for detailed study. The neuronal cells (and their associated phenotype) will then be used in a broad-based drug screen covering hundreds of thousands of existing drugs and other non-commercialized compounds. This project is in phase one and is expected to last up to three years, with a goal of identifying a potential drug candidate for testing on human Kleefstra Syndrome patients.

GeneSpark is now funding three distinct research projects, all approved by our Scientific Advisory Board in 2016 and described in detail below. Our progress to date would not be possible without our donors. All funds raised specifically through GlobalGiving Foundation have been applied to a portion of the funding requirement for the second project below. Once again, we thank you for your continued support!

Project 1: Kleefstra Syndrome - Focused Drug Screen on Human iPSC-derived Neurons and Subsequent Mouse Testing of Lead Compounds

Our first project formally began in December 2016 and is being led by Dr. Hans van Bokhoven and Dr. Nael Nadif Kasri, both of Radboud University (The Netherlands), in collaboration with Dr. Hans Bjornsson of Johns Hopkins University in the United States. The leaders of this research team have completed a screen of a short list of chemical compounds (drugs). They leveraged drugs that have historically been able to target syndromes and diseases which are similar to Kleefstra Syndrome, and other drugs well-suited to address the biology of Kleefstra Syndrome itself. How exactly did this screen work? The Radboud team had previously developed Kleefstra Syndrome neurons (brain cells), derived from a patient’s skin sample, through an innovative process involving induced pluripotent stem cell (iPSC) technology. These neurons resided in a petri dish and were evaluated for deficiencies as compared to neurons from a healthy patient. The team began testing the impact of the selected chemical compounds to assess their ability to improve noted deficiencies. After the initial screen of the compounds, the team identified one particular compound which showed significant promise in improving neuronal deficiencies. To our knowledge, this is the first time in history that a specific compound has been shown to improve or reverse Kleefstra Syndrome in a lab environment, in any kind of human or animal model. However, it is important to keep in mind that drug development is a complex and involved process, and this progress will require significant follow-up testing and validation over a multi-year period. Pending approval from our Scientific Advisory Board, the research team will advance the compound to mouse testing in order to better understand the behavioural and cognitive impacts. This next phase of the project is expected to last up to two and a half years, with a goal of identifying a potential drug candidate for testing on human Kleefstra Syndrome patients. 

Project 2: Screening Potential Drugs To Upregulate EHMT1 (Kleefstra Syndrome Gene)

Our second project is also underway and is being led by Dr. Carl Ernst of McGill University and Douglas Hospital Research Institute in Canada. Dr. Ernst is in the process of creating neuronal cells from a Kleefstra Syndrome patient’s skin sample to be used as a screening tool for chemical compounds, also leveraging iPSC technology. The screen will look for drugs that specifically increase the production of the EHMT1 protein, which is insufficiently produced in Kleefstra Syndrome patients. Why might this overall approach work? Like all humans, Kleefstra Syndrome patients are supposed to have two healthy copies of EHMT1. However, these patients’ gene mutations or deletions result in one copy being deficient. In identifying drugs that can successfully interact with, and stimulate increased production of EHMT1, we may be able to produce enough of the protein to compensate for the deficiency. This approach is known as “upregulation” and has proven successful in other diseases with similar challenges. Dr. Ernst will begin his work screening FDA-approved drugs and, given these drugs have already passed many hurdles, any early success may result in tremendous time and cost savings. This project is in its early phases and is expected to last up to two years from launch, with a goal of identifying a potential drug candidate for testing on human Kleefstra Syndrome patients.

Project 3: Kleefstra Syndrome: Broad-Based Drug Screen on Human iPSC-derived Neurons

Our third project is being led initially by Dr. Carl Ernst of McGill University in Canada, followed by phase-two leadership from Dr. Yi Zhang of Boston Children’s Hospital (BCH) in the United States. The BCH team will convert iPS cells (created by Dr. Ernst) to neuronal cells for detailed study. The neuronal cells (and their associated phenotype) will then be used in a broad-based drug screen covering hundreds of thousands of existing drugs and other non-commercialized compounds. This project is in phase one and is expected to last up to three years, with a goal of identifying a potential drug candidate for testing on human Kleefstra Syndrome patients.

In 2015, GeneSpark.org began raising money to fund scientific research projects aimed at advancing a drug treatment for Kleefstra Syndrome (KS). With the help of our partner organization, GlobalGiving Foundation, we made great progress toward our funding target and have now raised approximately C$762,000 globally. Based on recommendations of our Scientific Advisory Board (SAB), GeneSpark.org made the decision to deploy some of these funds on various research projects.

The first project formally began in December 2016 and is being led by Dr. Hans van Bokhoven and Dr. Nael Nadif Kasri, both of Radboud University (The Netherlands), in collaboration with Dr. Hans Bjornsson of Johns Hopkins University in the United States. The leaders of this research team have assembled and are beginning to screen a short list of chemical compounds, leveraging those that have historically been able to target syndromes and diseases that are similar to Kleefstra Syndrome (or those that may be best suited to tackle what is already known about the biology of Kleefstra Syndrome itself). How exactly will this screen work? The Radboud team has developed Kleefstra Syndrome neurons (brain cells) in a lab, with these neurons having been derived from a patient’s skin sample through a process involving induced pluripotent stem cell (iPSC) technology (iPSCs are a relatively new technology that enable neurons to be derived from disease patients). These disease-state neurons have been evaluated for deficiencies as compared to normal neurons, and the team will be able to test the impact of chemical compounds in terms of their ability to improve noted deficiencies. After an initial screen of the compounds, the team will advance the top candidates (which produce the most significant improvements) to test in Kleefstra Syndrome mice. Mice are an important part of the testing as they provide are a read on behavioral and intellectual changes. This project is expected to last up to three years, with a goal of identifying a potential drug candidate for testing on human Kleefstra Syndrome patients.

A second project was funded in January 2016 and is being led by Dr. Carl Ernst of McGill University in Canada. Dr. Ernst is in the process of creating neuronal or similar cells from a Kleefstra Syndrome patient’s skin sample that can be used as a screening tool for chemical compounds, also leveraging iPSC technology. The tool will screen for drugs that specifically increase the production of the key protein (EHMT1) implicated in Kleefstra Syndrome, as this protein is not produced in sufficient quantity in Kleefstra Syndrome patients. Why might this overall approach work? Kleefstra Syndrome patients have two copies of EHMT1 (just like the normal human population), with one copy functioning normally and the other being deficient (that deficiency is caused by the patient’s deletion or mutation). In working to identify drugs that can successfully interact with and stimulate increased production of the healthy copy of EHMT1, we may be able to compensate for the lack of EHMT1 production stemming from the unhealthy copy. This overall approach, known as “upregulation”, has proven successful in other diseases where one copy of the mutated/deleted gene was originally not producing in sufficient quantity. Dr. Ernst will begin his work screening FDA-approved drugs and, given these drugs have already passed many hurdles, any early successes could result in tremendous time and cost savings. This project is expected to last up to two years, with a goal of identifying a potential drug candidate for testing on human Kleefstra Syndrome patients.

Our progress to date would not be possible without our donors. All funds raised specifically through GlobalGiving Foundation have been applied to a portion of the funding requirement for the second project described above. Once again, we thank you for your continued support!

In 2015, GeneSpark.org began raising money to fund scientific research projects aimed at advancing a drug treatment for Kleefstra Syndrome (KS). With the help of our partner organization, GlobalGiving Foundation, we made great progress toward our funding target and have now raised approximately C$700,000 globally. Based on recommendations of our Scientific Advisory Board (SAB), GeneSpark.org made the decision to immediately begin the process to deploy some of these funds on two specific research projects.

The first project formally began in December 2016 and is being led by Dr. Hans van Bokhoven and Dr. Nael Nadif Kasri, both of Radboud University (The Netherlands), in collaboration with Dr. Hans Bjornsson of Johns Hopkins University in the United States. The leaders of this research team will assemble and screen a short list of chemical compounds, leveraging those that have historically been able to target syndromes and diseases that are similar to Kleefstra Syndrome (or those that may be best suited to tackle what is already known about the biology of Kleefstra Syndrome itself). How exactly will this screen work? The Radboud team has developed Kleefstra Syndrome neurons (brain cells) in a lab, with these neurons having been derived from a patient’s skin sample through a process involving induced pluripotent stem cell (iPSC) technology (iPSCs are a relatively new technology that enable neurons to be derived from disease patients). These disease-state neurons have been evaluated for deficiencies as compared to normal neurons, and the team will be able to test the impact of chemical compounds in terms of their ability to improve noted deficiencies. After an initial screen of the compounds, the team will advance the top candidates (which produce the most significant improvements) to test in Kleefstra Syndrome mice. Mice are an important part of the testing as they provide are a read on behavioral and intellectual changes. This project is expected to last up to three years, with a goal of identifying a potential drug candidate for testing on human Kleefstra Syndrome patients.

The second project is being led by Dr. Carl Ernst of McGill University in Canada. Dr. Ernst will create neuronal or similar cells from a Kleefstra Syndrome patient’s skin sample that can be used as a screening tool for chemical compounds, also leveraging iPSC technology. The tool will screen for drugs that specifically increase the production of the key protein (EHMT1) implicated in Kleefstra Syndrome, as this protein is not produced in sufficient quantity in Kleefstra Syndrome patients. Why might this overall approach work? Kleefstra Syndrome patients have two copies of EHMT1 (just like the normal human population), with one copy functioning normally and the other being deficient (that deficiency is caused by the patient’s deletion or mutation). In working to identify drugs that can successfully interact with and stimulate increased production of the healthy copy of EHMT1, we may be able to compensate for the lack of EHMT1 production stemming from the unhealthy copy. This overall approach, known as “upregulation”, has proven successful in other diseases where one copy of the mutated/deleted gene was originally not producing in sufficient quantity. Dr. Ernst will begin his work screening FDA-approved drugs and, given these drugs have already passed many hurdles, any early successes could result in tremendous time and cost savings. This project is expected to last up to two years, with a goal of identifying a potential drug candidate for testing on human Kleefstra Syndrome patients.

Our progress to date would not be possible without our donors. We expect that those funds raised specifically through GlobalGiving Foundation will be applied (during the course of 2017) to the initial phases of one or both of the projects described above. Once again, we thank you for your continued support!

In 2015, GeneSpark.org began raising money to fund scientific research projects aimed at advancing a drug treatment for Kleefstra Syndrome (KS). With the help of our partner organization, GlobalGiving Foundation, we made great progress toward our funding target. Since the launch of our efforts, we raised approximately C$400,000 across the world.

Early in 2016, GeneSpark.org launched a formal process to solicit research proposals from scientific teams around the world. These teams were screened and identified over the course of the past year to ensure that their experience bases and interests matched the needs of our Kleefstra Syndrome research goals. Since launching our formal research solicitation process, GeneSpark.org received a number of compelling proposals which were reviewed by our Scientific Advisory Board (SAB). The SAB is multi-disciplinary team which brings together a mix of research and commercial experience covering drug discovery, epigenetics, genetics, neurodevelopmental disorders, preclinical and clinical trials, venture capital and biotech management. The SAB completed its review and project selection process in early June. Based on recommendations of the SAB, GeneSpark.org expects to begin funding the initial phases of two research projects this fall. More details on these two research projects can be found on GeneSpark.org's website under the Scientific Research (Current Projects) section.

Our progress to date would not be possible without our donors. Once again, we thank you for your continued support!

In 2015, GeneSpark.org began raising money to fund scientific research projects aimed at advancing a drug treatment for Kleefstra Syndrome (KS). With the help of our partner organization, GlobalGiving Foundation, we made great progress toward our funding target. Since the launch of our efforts, we raised over C$300,000 across the world.

Early in 2016, GeneSpark.org launched a formal process to solicit research proposals from scientific teams around the world. These teams were screened and identified over the course of the past year to ensure that their experience bases and interests matched the needs of our Kleefstra Syndrome research goals. Since launching our formal research solicitation process, GeneSpark.org received a number of compelling proposals which were reviewed by our Scientific Advisory Board (SAB). The SAB is multi-disciplinary team which brings together a mix of research and commercial experience covering drug discovery, epigenetics, genetics, neurodevelopmental disorders, preclinical and clinical trials, venture capital and biotech management. The SAB completed its review and project selection process in early June. Based on recommendations of the SAB, GeneSpark.org expects to begin funding the initial phases of two research projects in the coming months. More details on these two research projects will be provided once funding begins.

Our progress to date would not be possible without our donors. Once again, we thank you for your continued support!

In 2015, GeneSpark.org began raising money to fund scientific research projects aimed at advancing a drug treatment for Kleefstra Syndrome (KS). With the help of our partner organizations, such as GlobalGiving Foundation, we made great progress toward our funding target. Since the launch of our efforts, we raised a total of almost C$300,000 across the world.

Early in 2016, GeneSpark.org launched a formal process to solicit research proposals from scientific teams around the world. These teams were screened and identified over the course of the past year to ensure that their experience bases and interests matched the needs of our Kleefstra Syndrome research goals. Since launching our formal reseach soliciation process, GeneSpark.org has received a number of compelling proposals which are now being reviewed by our Scientific Advisory Board (SAB). The SAB is multi-disciplinary team which brings together a mix of research and commercial experience covering drug discovery, epigenetics, genetics, neurodevelopmental disorders, preclinical and clinical trials, venture capital and biotech management. The SAB expects to complete its review and project selection process over the course of March and April of this year. Once complete, GeneSpark.org expects to begin funding the first (initial) phases of one or two research projects shortly thereafter.

Our progress to date would not be possible without our donors. We thank for your support and look forward to providing additional details on the project(s) that get funded in the coming months.