REQUEST FOR PROPOSALS: Environmentally Induced Germline Perturbations in the Etiology of Autism and Neurodevelopmental Disorders
Application deadline: May 1, 2014; $25,000 grant available, plus two $5,000 mini-grants
Background:
The past three decades have seen a staggering increase in the number of children diagnosed with the devastating neurodevelopmental disability of autism, creating an unprecedented and enduring national catastrophe with up to a million young Americans now incapacitated to varying degrees by what was once a rare disorder. In California alone, based on data kept by the Department of Developmental Services, substantially disabling autism has soared more than 2,000% since the early 1980s.
The skyrocketing rates have baffled families, scientists and practitioners, because though autism appeared to be strongly heritable (among siblings, not parent-to-child), the idea of a “genetic epidemic” made little sense in light of the understanding that genes could not change so dramatically in the course of a single generation.
It has come to light, however, that heritability also includes environmentally sensitive layers of molecular germline genetic regulation often referred to as the “epigenome.” Germ cells — eggs, sperm, and their precursors — contain countless millions of epigenetic marks that control how genes function, and these cells are susceptible to perturbation in critical windows, including early embryogenesis, a time of dynamic and widespread epigenetic remodeling of chromatin. Disruption of germline epigenetics can cause permanent dysregulation of sensitive genes, leading to pathology in offspring.
The 1950s, 60s, and 70s saw unprecedented use of potent synthetic chemicals administered, for example, as various prenatal pharmaceutical therapies during an era when the medical profession embraced burgeoning offerings of new synthetic drugs with little questioning of safety or efficacy while also considering the placenta a barrier to harm. However, it is now understood that a pregnancy exposures affect three generations simultaneously: the mother (F0), the fetus (F1), and the fetal germ cells (F2). Based on what we are learning from animal models, some F0 exposures potentially caused derangements to delicate fetal germline (the F2), theoretically giving rise to developmental or behavioral abnormality in the next generation, born in the 1970s, 80s, 90s, 00s.
The purpose of this RFP is to foster projects, including scientific research, conferences, meetings, and/or publications, which can help shed light on the paradigm-shifting hypothesis that a portion of today’s epidemics of autism and neurodevelopmental abnormality may be attributable to unforeseen disruptive effects of direct germline exposures.
Exposures of concern may include but are not limited to:
• Prescription pharmaceutical drugs used in the 1950s, 60s, and 70s: Including synthetic hormones (for example, progestins, estrogens, glucocorticoids used in once-common prophylactic “anti-miscarriage” protocols and for “treatment” of diverse pregnancy complications and ostensible risks), sedatives (for example, barbiturates and benzodiazapenes), anti-nausea drugs, amphetamines, psychoactive drugs, and anaesthesia.
• Prescription pharmaceutical drugs commonly used today: Including IVF hormone drugs, steroid drugs, antidepressants, diabetes drugs, PPIs, opioids, statins.
• Over the counter drugs used at any time: Including pain medications and heartburn drugs.
• Other acute exposures: For example, to endocrine-disrupting chemicals, military exposures, vocational exposures, radiation, smoking, tobacco.
Critical windows of germline development may include but are not limited to:
• Fetal germline: Germline development within the embryo and fetus, from specification of the primordial germ cells at about 5 weeks gestation to birth.
• Periconceptional period: The egg one month before conception, to early embryo one month after conception.
• Spermatogenesis: The sensitive 74-day period of sperm maturation prior to conception.
Phenotypic outcomes may include but are not limited to:
• Autism spectrum disorders
• Aspergers
• PDD-NOS
• ADHD/ ADD
• Sensory processing disorders
• Learning disabilities
• Social development disorders
• Communication disorders
• Behavioral/conduct disorders
• Mental illness
Examples of relevant projects (these are merely examples):
• Animal models: What are fetal germline and F2 outcomes of F0 exposure to SSRI drugs? Antinausea drugs? Synthetic hormone drugs?
• Epidemiology: Given a cohort of pregnancies for which there are reliable prenatal medical records dating from circa the 1960s, are F2 outcomes different when the F0 grandmother had been given pregnancy drugs, or smoked cigarettes, compared to controls?
• In vitro research: How do germ cell epigenetics respond if exposed to compounds known to affect gene expression and epigenetic mechanics, such as steroid hormone drugs?
• Case studies: Epigenetic assays of F2 ASD children where there is a known F0 gestational drug or smoking exposure. (The Fund could supply several families.)
• Meetings or symposia: Sessions at scientific meetings or conference panels or symposia about this topic.
• Conferences: Funding for a small conference focused on germline disruption in autism and neurodevelopmental disorders.
• Publications or articles: Funding for articles or publication that help educate the science, regulatory, or lay community about this topic.
• Policy efforts: Efforts to mandate retention and availability of prenatal medical records; efforts to educate the FDA about germline epigenetic vulnerabilities.
Depending on grantee progress, further support may be available.
To apply
Your application must include the following information:
• Amount of request: $25k is the maximum, but requests for smaller amounts will also be considered and may be given priority. Two $5k mini-grants are also available. This grant may be used to augment or leverage other awards or projects.
• Tax status of requestor: Grants can be given through 501c3 or otherwise qualifying nonprofit organizations or institutions only.
• Project description: (1000 word maximum)
--Objective of the project or study
--Methods to be used or details of the project
--Collaborators
--Line item description of how grant money would be used
--Statement concerning indirect costs. The applicant must stipulate that no more than 5% of grant funds will support indirect costs.
--If proposing a project/talk/symposium/conference what the collaborators hope to deliver at the end, and how it will move the field forward.
--Timeline: Projects must be completed within a year of the grant.
Deadline to submit proposals via email to [email protected] is May 1, 2014.
Sponsored by the Escher Fund for Autism
Application deadline: May 1, 2014; $25,000 grant available, plus two $5,000 mini-grants
Background:
The past three decades have seen a staggering increase in the number of children diagnosed with the devastating neurodevelopmental disability of autism, creating an unprecedented and enduring national catastrophe with up to a million young Americans now incapacitated to varying degrees by what was once a rare disorder. In California alone, based on data kept by the Department of Developmental Services, substantially disabling autism has soared more than 2,000% since the early 1980s.
The skyrocketing rates have baffled families, scientists and practitioners, because though autism appeared to be strongly heritable (among siblings, not parent-to-child), the idea of a “genetic epidemic” made little sense in light of the understanding that genes could not change so dramatically in the course of a single generation.
It has come to light, however, that heritability also includes environmentally sensitive layers of molecular germline genetic regulation often referred to as the “epigenome.” Germ cells — eggs, sperm, and their precursors — contain countless millions of epigenetic marks that control how genes function, and these cells are susceptible to perturbation in critical windows, including early embryogenesis, a time of dynamic and widespread epigenetic remodeling of chromatin. Disruption of germline epigenetics can cause permanent dysregulation of sensitive genes, leading to pathology in offspring.
The 1950s, 60s, and 70s saw unprecedented use of potent synthetic chemicals administered, for example, as various prenatal pharmaceutical therapies during an era when the medical profession embraced burgeoning offerings of new synthetic drugs with little questioning of safety or efficacy while also considering the placenta a barrier to harm. However, it is now understood that a pregnancy exposures affect three generations simultaneously: the mother (F0), the fetus (F1), and the fetal germ cells (F2). Based on what we are learning from animal models, some F0 exposures potentially caused derangements to delicate fetal germline (the F2), theoretically giving rise to developmental or behavioral abnormality in the next generation, born in the 1970s, 80s, 90s, 00s.
The purpose of this RFP is to foster projects, including scientific research, conferences, meetings, and/or publications, which can help shed light on the paradigm-shifting hypothesis that a portion of today’s epidemics of autism and neurodevelopmental abnormality may be attributable to unforeseen disruptive effects of direct germline exposures.
Exposures of concern may include but are not limited to:
• Prescription pharmaceutical drugs used in the 1950s, 60s, and 70s: Including synthetic hormones (for example, progestins, estrogens, glucocorticoids used in once-common prophylactic “anti-miscarriage” protocols and for “treatment” of diverse pregnancy complications and ostensible risks), sedatives (for example, barbiturates and benzodiazapenes), anti-nausea drugs, amphetamines, psychoactive drugs, and anaesthesia.
• Prescription pharmaceutical drugs commonly used today: Including IVF hormone drugs, steroid drugs, antidepressants, diabetes drugs, PPIs, opioids, statins.
• Over the counter drugs used at any time: Including pain medications and heartburn drugs.
• Other acute exposures: For example, to endocrine-disrupting chemicals, military exposures, vocational exposures, radiation, smoking, tobacco.
Critical windows of germline development may include but are not limited to:
• Fetal germline: Germline development within the embryo and fetus, from specification of the primordial germ cells at about 5 weeks gestation to birth.
• Periconceptional period: The egg one month before conception, to early embryo one month after conception.
• Spermatogenesis: The sensitive 74-day period of sperm maturation prior to conception.
Phenotypic outcomes may include but are not limited to:
• Autism spectrum disorders
• Aspergers
• PDD-NOS
• ADHD/ ADD
• Sensory processing disorders
• Learning disabilities
• Social development disorders
• Communication disorders
• Behavioral/conduct disorders
• Mental illness
Examples of relevant projects (these are merely examples):
• Animal models: What are fetal germline and F2 outcomes of F0 exposure to SSRI drugs? Antinausea drugs? Synthetic hormone drugs?
• Epidemiology: Given a cohort of pregnancies for which there are reliable prenatal medical records dating from circa the 1960s, are F2 outcomes different when the F0 grandmother had been given pregnancy drugs, or smoked cigarettes, compared to controls?
• In vitro research: How do germ cell epigenetics respond if exposed to compounds known to affect gene expression and epigenetic mechanics, such as steroid hormone drugs?
• Case studies: Epigenetic assays of F2 ASD children where there is a known F0 gestational drug or smoking exposure. (The Fund could supply several families.)
• Meetings or symposia: Sessions at scientific meetings or conference panels or symposia about this topic.
• Conferences: Funding for a small conference focused on germline disruption in autism and neurodevelopmental disorders.
• Publications or articles: Funding for articles or publication that help educate the science, regulatory, or lay community about this topic.
• Policy efforts: Efforts to mandate retention and availability of prenatal medical records; efforts to educate the FDA about germline epigenetic vulnerabilities.
Depending on grantee progress, further support may be available.
To apply
Your application must include the following information:
• Amount of request: $25k is the maximum, but requests for smaller amounts will also be considered and may be given priority. Two $5k mini-grants are also available. This grant may be used to augment or leverage other awards or projects.
• Tax status of requestor: Grants can be given through 501c3 or otherwise qualifying nonprofit organizations or institutions only.
• Project description: (1000 word maximum)
--Objective of the project or study
--Methods to be used or details of the project
--Collaborators
--Line item description of how grant money would be used
--Statement concerning indirect costs. The applicant must stipulate that no more than 5% of grant funds will support indirect costs.
--If proposing a project/talk/symposium/conference what the collaborators hope to deliver at the end, and how it will move the field forward.
--Timeline: Projects must be completed within a year of the grant.
Deadline to submit proposals via email to [email protected] is May 1, 2014.
Sponsored by the Escher Fund for Autism