Parents Find Glimpse of Hope For Treatment of Their Children's Rare Genetic Disorder.
SUMMARY:
It's a compelling story; a parent learns their child has a rare life threatening disease with no treatment and no cure, though not a scientist in rare disease, embarks on a quest to find treatment. It is a story you hear in the rare disease space time and time again. But most of those stories almost always fail because of the difficulty in getting large pharmaceutical companies to grab the very expensive baton of developing a new drug for a small rare disease affecting children.
Still some parents, have chosen to take matters into their own hands to help their children by getting involved in science, drug discovery and advocacy.
Sandra Sermone, Washington and Matt Davis, Alabama, are parents of children with ADNP syndrome who started thinking outside the box when it comes to accelerating drug development for children with ADNP syndrome and they have chosen to embark on the possibly quicker and somewhat less expensive route of repurposed drugs. Repurposed drugs come from investigating existing drugs for new therapeutic purposes, ones that are already FDA approved for another condition, to provide the quickest possible transition from bench to bedside.
Enter another rare disease parent Matt Might, Alabama, to the picture. Sandra had known Matt for years through their connections in the rare disease space. Both Might's and Sermone's sons had been diagnosed with different rare genetic disorders at Duke University just months apart from one another. Years later, Might and Davis found themselves both working together at UAB. Might, using his AI technology, gave a list of possible drug options with ketamine being one of them, and Davis and Sermone were off to to the races. "Small grassroots rare disease patient organizations like ours could never utilize this type of technology without people like Matt Might who has created a system where he can come up with some connections and then let the patient organizations move forward with all of the work needed to investigate the viability and do all of the work to move a drug to trial.
It's a compelling story; a parent learns their child has a rare life threatening disease with no treatment and no cure, though not a scientist in rare disease, embarks on a quest to find treatment. It is a story you hear in the rare disease space time and time again. But most of those stories almost always fail because of the difficulty in getting large pharmaceutical companies to grab the very expensive baton of developing a new drug for a small rare disease affecting children.
Still some parents, have chosen to take matters into their own hands to help their children by getting involved in science, drug discovery and advocacy.
Sandra Sermone, Washington and Matt Davis, Alabama, are parents of children with ADNP syndrome who started thinking outside the box when it comes to accelerating drug development for children with ADNP syndrome and they have chosen to embark on the possibly quicker and somewhat less expensive route of repurposed drugs. Repurposed drugs come from investigating existing drugs for new therapeutic purposes, ones that are already FDA approved for another condition, to provide the quickest possible transition from bench to bedside.
Enter another rare disease parent Matt Might, Alabama, to the picture. Sandra had known Matt for years through their connections in the rare disease space. Both Might's and Sermone's sons had been diagnosed with different rare genetic disorders at Duke University just months apart from one another. Years later, Might and Davis found themselves both working together at UAB. Might, using his AI technology, gave a list of possible drug options with ketamine being one of them, and Davis and Sermone were off to to the races. "Small grassroots rare disease patient organizations like ours could never utilize this type of technology without people like Matt Might who has created a system where he can come up with some connections and then let the patient organizations move forward with all of the work needed to investigate the viability and do all of the work to move a drug to trial.
It all began last year, Sermone and Davis started looking into repurposed drug development after a 2018 peptide potential trial for a drug called CP201 seemed to come to a complete stop. During that time, Might brought ketamine to Davis' attention. Davis believed this had some potential and approached Sermone. Davis was able to pull relevant medical publications because of his academic background and Sermone started compiling the data to present to their research team, attended biotech and drug development conferences and began the process of IP. They researched hundreds of pages of medical literature, contacted and spoke to other scientists who had also worked on ketamine for other rare diseases and collected relevant data to build a case for low-dose ketamine as quickly as they could. They strongly believe low-dose ketamine may help their children. Sermone then took their findings and to Dr. Joseph Buxbaum, Director of the Seaver Autism Center for Research and Treatment at Mount Sinai in New York. After Sermone submitted additional information, his team, led by Dr. Alex Kolevzon, felt this could be a viable treatment and Kolevzon took the lead.
Ketamine is already FDA approved safe in children at sedation levels, but this study aims to use low dose levels for treatment. Ketamine has made headlines recently when it obtained FDA approval in intranasal esketamine (SpravatoÒ) for treatment-resistant depression. However, and important for ADNP syndrome, studies in animal models suggest that low-dose ketamine may increase expression of ADNP in nerve cells. For this reason, treatment with low-dose ketamine may have beneficial effects in individuals with ADNP syndrome by compensating for ADNP insufficiency and could increase the protein and possibly be therapeutic.
"This model of patient involved research is crucial to driving breakthroughs in science for rare disease. We are desperate and it's up to us to try to do everything that we can and push like hell for drug discovery because no one else is going to care more about our children than we are", says Sermone.
In November 2019, at the first ADNP Family Conference, Sermone with Kolevzon, announced to the ADNP community that they were moving forward to start the first ever clinical trial for ADNP Syndrome.
Kolevzon wasted no time, and in just over a month, designed the clinical trial plans and submitted the study to the FDA in December. Less than two months later approval came from the FDA saying the trial was safe to proceed to the phase 2 study of ketamine as treatment for ADNP.
Ketamine is already FDA approved safe in children at sedation levels, but this study aims to use low dose levels for treatment. Ketamine has made headlines recently when it obtained FDA approval in intranasal esketamine (SpravatoÒ) for treatment-resistant depression. However, and important for ADNP syndrome, studies in animal models suggest that low-dose ketamine may increase expression of ADNP in nerve cells. For this reason, treatment with low-dose ketamine may have beneficial effects in individuals with ADNP syndrome by compensating for ADNP insufficiency and could increase the protein and possibly be therapeutic.
"This model of patient involved research is crucial to driving breakthroughs in science for rare disease. We are desperate and it's up to us to try to do everything that we can and push like hell for drug discovery because no one else is going to care more about our children than we are", says Sermone.
In November 2019, at the first ADNP Family Conference, Sermone with Kolevzon, announced to the ADNP community that they were moving forward to start the first ever clinical trial for ADNP Syndrome.
Kolevzon wasted no time, and in just over a month, designed the clinical trial plans and submitted the study to the FDA in December. Less than two months later approval came from the FDA saying the trial was safe to proceed to the phase 2 study of ketamine as treatment for ADNP.
PANDEMIC SHUTS DOWN THE COUNTRY
Just as the team was receiving the go ahead to move forward with the study from the FDA, the COVID-10 pandemic hit and shut down the Seaver Autism Center, but this did not stop the team from pushing forward full speed ahead to begin this drug trial.
Kolevzon worked from home, creating all regulatory protocols, proposals and submitting all applications needed through Mount Sinai to begin the trial. He pushed this through and received all approvals in a matter of months. Additionally, Kolevzon was able to request a reduced cost for the trial knowing that it was parents fundraising through the foundation to pay for the drug trial. "Alex is an amazing person. Who goes to bat this hard for a small rare disease like this, works from home and begins a drug trial during a pandemic? He is an incredible physician who cares deeply for his patients and in helping our children", says Sermone.
In May of 2020, only 6 months after announcing the decision to start a clinical trial, the study officially began and enrollment and launched the first ever drug trial for ADNP Syndrome - Low-Dose Ketamine for Treatment in Children with ADNP Syndrome.
The foundation moved forward with fundraising efforts and held a virtual "Warrior Fun Run", creating teams all around the world to raise month for the phase 2 study. Sermone said that "without the amazing families and friends who joined and supported the Warrior Fun Run, it would have been impossible to start the clinical trial so quickly. We seriously thought this was going to take us 6 months to a year to raise that much money during a pandemic, but our ADNP families and friends came to the rescue just as the title of the fundraiser implies, like "warriors", and they raised over $150,000 in just over one month. It is a true testimony that we have the greatest community of ADNP families and without their support, none of this would be possible"
By August, just 9 months after announcing the decision to start the clinical trial, the first patient was seen in clinic! "We did it", said Sermone, "at a speed that is unheard of, and we plan to continue to move forward safely and as quickly as possible to help our children. From start to finish, the small phase 2 and larger phase 3 study is estimated to cost just over one million dollars which is a small fraction of what a normal drug trial would cost, so we are very lucky to have found a 'repurposed drug'; "It's not a cure, but for now, if we can improve the tiniest thing, and give these kids even a slightly brighter tomorrow than they have today, it will be a dream". said Sermone.
ADNP Syndrome is an ultra rare neurological genetic condition which causes intellectual and neurodevelopmental disabilities, speech delays, autism, seizures, low muscle tone, cardiac and brain abnormalities, and is currently diagnosed in less than 250 children in the world.
In January 2020, in the largest genetic sequencing study of autism spectrum disorder (ASD) to date (CELL Journal), researchers identified the "ADNP gene" as one of the top genes related to autism and neurodevelopmental dysfunction. The landmark study was led by Joseph Buxbaum, PhD, Director of the Seaver Autism Center for Research and Treatment at Mount Sinai. Buxbaum has told Sermone that he believes ADNP could likely be more prevalent than Rett Syndrome and may rival Fragile X in the number of patients, but without awareness and easy-low cost global testing, patients are not getting diagnosed.
For more information on ADNP Syndrome, visit www.adnpfoundation.org
RELATED RECENT NEWS STORIES:
https://health.mountsinai.org/blog/new-clinical-trial-will-test-whether-ketamine-can-be-used-to-treat-children-with-autism/
AND
https://www.mountsinai.org/about/newsroom/2020/seaver-autism-center-for-research-and-treatment-at-mount-sinai-launches-first-drug-trial-for-adnp-syndrome-pr
Just as the team was receiving the go ahead to move forward with the study from the FDA, the COVID-10 pandemic hit and shut down the Seaver Autism Center, but this did not stop the team from pushing forward full speed ahead to begin this drug trial.
Kolevzon worked from home, creating all regulatory protocols, proposals and submitting all applications needed through Mount Sinai to begin the trial. He pushed this through and received all approvals in a matter of months. Additionally, Kolevzon was able to request a reduced cost for the trial knowing that it was parents fundraising through the foundation to pay for the drug trial. "Alex is an amazing person. Who goes to bat this hard for a small rare disease like this, works from home and begins a drug trial during a pandemic? He is an incredible physician who cares deeply for his patients and in helping our children", says Sermone.
In May of 2020, only 6 months after announcing the decision to start a clinical trial, the study officially began and enrollment and launched the first ever drug trial for ADNP Syndrome - Low-Dose Ketamine for Treatment in Children with ADNP Syndrome.
The foundation moved forward with fundraising efforts and held a virtual "Warrior Fun Run", creating teams all around the world to raise month for the phase 2 study. Sermone said that "without the amazing families and friends who joined and supported the Warrior Fun Run, it would have been impossible to start the clinical trial so quickly. We seriously thought this was going to take us 6 months to a year to raise that much money during a pandemic, but our ADNP families and friends came to the rescue just as the title of the fundraiser implies, like "warriors", and they raised over $150,000 in just over one month. It is a true testimony that we have the greatest community of ADNP families and without their support, none of this would be possible"
By August, just 9 months after announcing the decision to start the clinical trial, the first patient was seen in clinic! "We did it", said Sermone, "at a speed that is unheard of, and we plan to continue to move forward safely and as quickly as possible to help our children. From start to finish, the small phase 2 and larger phase 3 study is estimated to cost just over one million dollars which is a small fraction of what a normal drug trial would cost, so we are very lucky to have found a 'repurposed drug'; "It's not a cure, but for now, if we can improve the tiniest thing, and give these kids even a slightly brighter tomorrow than they have today, it will be a dream". said Sermone.
ADNP Syndrome is an ultra rare neurological genetic condition which causes intellectual and neurodevelopmental disabilities, speech delays, autism, seizures, low muscle tone, cardiac and brain abnormalities, and is currently diagnosed in less than 250 children in the world.
In January 2020, in the largest genetic sequencing study of autism spectrum disorder (ASD) to date (CELL Journal), researchers identified the "ADNP gene" as one of the top genes related to autism and neurodevelopmental dysfunction. The landmark study was led by Joseph Buxbaum, PhD, Director of the Seaver Autism Center for Research and Treatment at Mount Sinai. Buxbaum has told Sermone that he believes ADNP could likely be more prevalent than Rett Syndrome and may rival Fragile X in the number of patients, but without awareness and easy-low cost global testing, patients are not getting diagnosed.
For more information on ADNP Syndrome, visit www.adnpfoundation.org
RELATED RECENT NEWS STORIES:
https://health.mountsinai.org/blog/new-clinical-trial-will-test-whether-ketamine-can-be-used-to-treat-children-with-autism/
AND
https://www.mountsinai.org/about/newsroom/2020/seaver-autism-center-for-research-and-treatment-at-mount-sinai-launches-first-drug-trial-for-adnp-syndrome-pr
ADDITIONAL INFORMATION:
ADNP SYNDROME:
ADNP Syndrome is an extremely rare neurodevelopmental genetic disorder caused by a change on the ADNP gene (one of the genes identified in the landmark study noted above), which is a master brain gene that affects brain formation, connectivity, development and function. It also regulates over 400 other genes and affects many different organs and functions of the body. This debilitating syndrome can cause problems with almost all systems of the body. Developmentally, it can cause delays in cognition, speech and global motor planning. ADNP is highly linked to autism as one of the top autism related genes. However, most children who are less affected have never had genetic testing and their families have no idea that there could be a genetic cause for their child’s autism or developmental delays.
ADNP SYNDROME:
ADNP Syndrome is an extremely rare neurodevelopmental genetic disorder caused by a change on the ADNP gene (one of the genes identified in the landmark study noted above), which is a master brain gene that affects brain formation, connectivity, development and function. It also regulates over 400 other genes and affects many different organs and functions of the body. This debilitating syndrome can cause problems with almost all systems of the body. Developmentally, it can cause delays in cognition, speech and global motor planning. ADNP is highly linked to autism as one of the top autism related genes. However, most children who are less affected have never had genetic testing and their families have no idea that there could be a genetic cause for their child’s autism or developmental delays.
IF YOU SUSPECT THAT YOUR CHILD OR FAMILY MEMBER MAY HAVE ADNP SYNDROME, PLEASE TALK TO THEIR DOCTOR ABOUT GENETIC TESTING.
Two US based labs that offer full tests or panels are Ambry Genetics and GeneDx, both seem to be used at most accademic and children's hospitals.
GENE DX AUTISM XPANDED PANEL
GENE DX AUTISM/ID PANEL
AMBRY GENETICS MULTIPLE PANEL
updated 5/1/2020
Two US based labs that offer full tests or panels are Ambry Genetics and GeneDx, both seem to be used at most accademic and children's hospitals.
GENE DX AUTISM XPANDED PANEL
GENE DX AUTISM/ID PANEL
AMBRY GENETICS MULTIPLE PANEL
updated 5/1/2020
