To Our Friends & Supporters,

Many thanks for your continuing support of the Juvenile Bipolar Research Foundation. All progress we make is attributable to your extraordinarily consistent generosity.

Your contributions have helped fund research that has resulted in ground‐breaking studies that identified a novel subtype, and an effective treatment for the most severe form of juvenile‐onset bipolar disorder (referred to as the Fear of Harm subtype). The research led to a major expansion of knowledge in the field.

This year, Foundation researchers completed the ”first” open‐label, long‐term study of intranasal ketamine treatment for the Fear of Harm subtype, a pioneering effort that demonstrated safety and a robust effectiveness for the condition which affects more than one‐third of bipolar children.

This success would ordinarily be followed by what is known as a double‐blind placebo‐ controlled study, the gold standard assessment of a drug’s effectiveness. However, without long‐term animal studies to provide further safety data, the FDA would limit such a trial to 8 administrations of the drug. Knowledge accrued from the open label human studies inform us that effectiveness was demonstrated only after 10‐14 treatments.

Because of this FDA imposed restriction, funds intended for that study will be re‐allocated to new initiatives that will further our understanding of the underlying biological and genetic basis of the Fear of Harm subtype, as well as promote its awareness in the psychiatric community and families who deal with the illness.

With advances in brain imaging, and in collaboration with researchers from Harvard Medical School, the foundation seeks additional support for an fMRI study (a special type of brain imaging analysis) that could reveal important differences in neuronal activity in specific regions of the brain, before and after ketamine administration, in individuals that have demonstrated a therapeutic response.

Teaming with researchers from the Albert Einstein College of Medicine, support is also sought for a program to establish pluripotent stem cells (iPSC’s) from patients with childhood‐onset forms of bipolar disorder. iPSC’s can be turned into any cell type in the body, including neurons. The study of patient‐specific neurons with iPSC technology will provide a unique opportunity to understand the underlying biological basis, a major first step in new drug discovery.

Please make a commitment to support our mission to advance the understanding of juvenile‐onset bipolar disorder.

Action Plan for New Research

A Functional Magnetic Imaging (fMRI) Study of the Fear of Harm phenotype (FOH): The aim of this study is to explore differences in activation and connectivity patterns in the central nervous system between individuals with FOH and age/sex matched controls using state of the art fMRI imaging techniques pre and post ketamine treatment that is coupled with specific stimuli, including, the projection of fearful faces and skin cooling with menthol. The aim is to elucidate whether these stimuli elicit different brain activation patterns in comparison groups.
Budget: $225,000

Thermoregulatory Dysfunction: In a discrete subgroup of children and adolescents, about 1/3rd of a general population sample (n=6000) diagnosed with bipolar disorder in the community were investigated on a broad range of clinical indicators. A putative heritable trait and a clear physiological marker associated was identified within this subgroup ‐ a deficit in thermoregulation, specifically, a disturbance in the ability to dissipate heat from the body. We have now discovered and are employing treatments that, in correcting the thermoregulatory disturbance, abolish the major symptoms, and dramatically modify the aggressive behaviors that are primarily a response to fear‐based misperceptions in these individuals.
To demonstrate that this thermoregulatory dysfunction is a heritable trait marker for the condition, an investigation of the occurrence of this phenomenon within families with an identified patient with FOH and bipolar disorder, in comparison to 50 families with an identified patient with bipolar disorder without this marker will be conducted.
Budget: $150,000

Modeling of neurological diseases: Using induced pluripotent stem cells (iPSC’s) derived from the cells of patients has provided a novel means to elucidate disease mechanisms. A genomic analysis of neural cells that originate from iPSC cells derived from patients with FOH, could enable investigators to elucidate the pathogenic mechanisms of this condition. We propose to establish stem cell lines from 5 patients diagnosed with FOH and 5 control subjects and induce the development of temperature sensitive hypothalamic cells to enable the availability of such cells for studies by the research community at large.
Budget: $2.25m