2018 Team Josh’s DCO Riders/Million Dollar Bike Ride Grant – Request for Applications

Principal Investigator: Orphan Disease Center at the University of Pennsylvania

Amount Awarded: $100,373

Lay summary:

The Orphan Disease Center (ODC) at the University of Pennsylvania is pleased to announce the 2018 Million Dollar Bike Ride Pilot Grant Program. The program is now open and offering 39 different research grant opportunities focusing on 23 different rare diseases. The following Request for Application (RFA) is specific to Dyskeratosis Congenita and Telomere Biology Disorders: 

Dyskeratosis Congenita & Telomere Biology Disorder: One $100,373 grant available to investigators conducting basic or clinical research on all aspects of Dyskeratosis Congenita

Telomere Biology Disorders. Dyskeratosis Congenita is a progressive, genetic condition caused by defects in telomeres, the protective caps at the ends of chromosomes. Impaired telomere maintenance in Dyskeratosis Congenita/Telomere Biology Disorders results in problems throughout the body, notably including blood, liver, and lung disease, and cancer. Proposals that seek to advance understanding of the genetics, biology, pathophysiology, disease manifestations, treatment, including late effects of stem cell transplant, natural history and/or outcomes of Dyskeratosis Congenita and telomere diseases will be considered. This grant is made possible by Team Josh’s DCO Riders.

This program provides a one‐year grant to support research related to a rare disease represented in the 2018 Million Dollar Bike Ride. A number of awards and dollar amounts vary per disease based on fundraising totals by each disease team. This Request for Applications (RFA) is open to the international community. All individuals holding a faculty‐level appointment at an academic institution or a senior scientific position at a non-profit institution or foundation are eligible to respond to this RFA.

For more details about this grant program, rare disease focus areas, and how to apply, please visit the ODC website here. The RFA Guidelines are attached for your reference. Letters of Interest (LOIs) are due no later than Monday, September 10, 2018, by 8 pm EST. Please refer to the ODC’s website for instructions on LOI submission.

A multi-center, prospective, minimal intensity BMT trial for dyskeratosis congenita

Principal Investigator: Suneet Agarwal, Boston Children’s Hospital

Amount Awarded: $50,000

Lay summary:
Bone marrow transplantation (BMT) is a life-saving therapy for many blood diseases, but the chemotherapy and radiation typically used in BMT cause life-threatening complications. For patients with the rare disease dyskeratosis (DC) who require BMT to cure their failing blood system, the toxicity and risks of BMT can be even more severe. We are conducting a clinical trial that asks whether DC patients can undergo BMT without using traditional “DNA-damaging” chemotherapy and radiation, in order to reduce the toxicity of the procedure and improve survival. The idea that this might work comes from an emerging understanding of the genetics and biology of DC. So far, a series of DC patients treated at one institution have successfully undergone BMT on this trial, making them the first group to obtain a cure for their failing blood systems without exposure to DNA damaging radiation and chemotherapy. Now, we aim to expand this trial to other major centers in the United States, as the first prospective multi-center BMT trial for DC. The 2016 Million Dollar Bike Ride Pilot Award from Team Josh and the DCO Riders will enable multi-center expansion of this clinical study, which promises to change the approach and outcome of BMT for DC patients.

Pharmacologic rescue of telomere defects in dyskeratosis congenita

Principal Investigator: Brad Johnson and Chris Lengner, University of Pennsylvania

Amount Awarded: $50,000

Lay summary: 
The primary problem underlying the diseases suffered by people with dyskeratosis congenita (DC) is a failure of telomerase to maintain telomeres in a functional, i.e. “capped” state. This failure is secondary to mutations that partially compromise the ability of telomerase to lengthen telomeres. It is not yet possible to repair these mutations in all the affected cells of people with DC, and so instead of taking a genetic approach to DC therapy, we are investigating a potential pharmacological approach that is based on our recent discovery of a positive feedback loop between telomere capping and the activity of the Wnt signaling pathway. Wnt signaling is one way that different types of neighboring cells can communicate with one another, and it is particularly important in the support of tissue stem cells that are critical for tissue health. We found that when telomeres are capped, Wnt signaling is active, which in turn, feeds back to support continued telomere capping. This virtuous cycle breaks down when telomeres become prematurely shortened in DC, and indeed becomes vicious as the decline in Wnt signaling leads to further telomere uncapping. We reported recently that pharmacologic enhancement of Wnt signaling (e.g. using inhibitors of an enzyme called GSK3) can restore telomere capping and stem cell and tissue health in models of DC intestinal defects. We are now testing the applicability of this approach in other tissues, including lung and liver. Of particular note, we have recently established Wnt pathway defects related to type II alveolar epithelial stem cell dysfunction in a human cultured lung organoid model derived from induced pluripotent stem cells bearing DC-causing mutations. Moreover, GSK3 inhibition rescues these lung epithelial defects, supporting the potential utility of Wnt pathway agonists in DC therapy.

Recreational activities allow children and adults to relax and make connections with other families impacted by DC/TBDs. While at Camp Sunshine, each family stays in their own suite, equipped with two twin beds, bunk beds, a futon, full bathroom, microwave oven, and refrigerator. Meals are provided in the dining room and are occasions for socializing and unwinding.

Psychosocial Support

Moderated parent groups are provided during Camp Sunshine sessions and are tailored to parents’ needs. These sessions are often the first opportunity parents have had to share their experiences with others in similar situations. The groups provide a forum in which parents can gain insight and support in dealing with illness-related issues.

Medical Support

A physician is available 24-hours a day throughout each session to support the medical needs of families attending Camp. In addition, a state-of-the-art children’s hospital is only 40 minutes from Camp, and an urgent care center and community hospital with fully staffed emergency rooms are 20 minutes away.

Volunteer Support

Camp Sunshine volunteers serve as camp counselors, and work in many areas of the program, including food service, arts and crafts, and a variety of other activities.