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NIH launches initiative to accelerate genetic therapies to cure sickle cell disease
The National Institutes of Health announced the launch of a new initiative to help speed the development of cures for sickle cell disease, a group of inherited blood disorders affecting at least 100,000 people in the United States and 20 million worldwide. The Cure Sickle Cell Initiative will take advantage of the latest genetic discoveries and technological advances to move the most promising genetic-based curative therapies safely into clinical trials within five to 10 years.
“Our scientific investments have brought us to a point where we have many tools available to correct or compensate for the defective gene that causes sickle cell disease. We are now ready to use these tools to speed up our quest for a cure,” said Gary H. Gibbons, M.D., director of NIH’s National Heart, Lung, and Blood Institute (NHLBI), which is leading the effort.
Sickle cell disease results from a single genetic mutation that causes a person’s red blood cells to form an abnormal, sickle shape. These sickled cells can clog the blood vessels and deprive cells of oxygen. In turn, this lack of oxygen wreaks havoc on the body, damaging organs, causing severe pain, and potentially leading to premature death.
Decades of basic research on sickle cell disease have laid the groundwork for novel genetic approaches to cures, such as the genetic editing of bone marrow cells, which have shown great promise in animal models and in some small scale human studies. In addition, the NHLBI Production Assistance for Cellular Therapies (PACT) program(link is external) has been working with researchers to manufacture cellular therapeutic products, including genetically modified cells, that can be used safely in clinical trials with patients.
NIH spends approximately $100 million on sickle cell disease research each year. Through this initiative, NHLBI seeks to support the development of cell and genetic therapies resources, clinical trials, comparator analyses of different management strategies, data repositories and resources, and patient and advocate engagement activities related to curative therapies for this condition. Already in 2018, NHLBI committed an additional $7 million to jumpstart the initiative’s research and engagement infrastructure.
NHLBI has named hematologist Edward J. Benz Jr., M.D., President and CEO Emeritus of Dana-Farber Cancer Institute, as the Initiative’s executive director, and the Emmes Corporation, a contract research organization with specialized expertise in clinical trials, gene and cell therapy development in preclinical studies, as its coordinating center.
The initiative and its research partners will establish a national data warehouse of genetic therapies for sickle cell disease and conduct comparative analyses of therapeutic approaches to assess both clinical and cost effectiveness. They will also establish national networks to make it easier for patients and providers to learn and engage with the research, clinical trials, and other activities happening across the country.
“The engagement of patients will be a cornerstone of this effort,” said Benz. “Patients will work alongside researchers in developing and recruiting for clinical trials.”
Currently, the only cure for sickle cell disease is a bone marrow transplant, a procedure in which a sick patient receives bone marrow from a healthy, genetically-compatible sibling donor. However, transplants are too risky for many adults, and only about 18 percent of children with sickle cell disease have a healthy, matched sibling donor.
The Cure Sickle Cell Initiative seeks to develop cures for a far broader group of individuals with the disease, and it is initially focusing on gene therapies that modify the patient’s own hematopoietic stem cells (HSCs), which make red and other blood cells. These modified HSCs can then be given back to the patient via a bone marrow transplant, making a cure available to more patients who lack a matched donor.
“This initiative is giving patients, families, and communities a reason for hope. I’m particularly pleased that we are able to make this announcement during Sickle Cell Awareness month, when we are shining a spotlight on the toll of this devastating disease,” said ADM Brett Giroir, M.D. Assistant Secretary for Health at the U.S. Department of Health and Human Services (HHS).
This patient-focused Initiative builds on the legacy of NHLBI-supported research that has contributed to improving clinical care for patients who have sickle cell disease. It also complements the Institute’s broader sickle cell disease research investment, which includes basic, clinical, translational, and implementation science research.
Presidential Message on National Sickle Cell Disease Awareness Month
During National Sickle Cell Disease Awareness Month, we stand with those fighting sickle cell disease (SCD) and reaffirm our Nation’s commitment to finding a cure for this group of hereditary red blood cell disorders.
SCD is a debilitating condition that affects more than 100,000 Americans of all ages by slowing or blocking blood flow, causing pain and progressive organ damage, and reducing life expectancy. While the disease disproportionately affects African Americans, other racial and ethnic groups can also be affected. Bone marrow and stem cell transplants are the only current forms of treatment with the potential to cure this disease. These procedures have a high disease-free survival rate, but it can be difficult to find a matching donor.
My Administration is committed to supporting research to develop a cure to SCD that is available to all people, expanding on the achievements of current treatment options. Clinical trials to accelerate the development of new gene and cell-based therapies within the next 5 to 10 years will be conducted as part of the National Institutes of Health’s Cure Sickle Cell Initiative, which will launch this month. Additionally, we are working to better train healthcare providers to identify individuals with SCD and improve the quality and continuity of their care from infancy through adulthood. As a result of the many advances and medical breakthroughs in genetic therapies and research, we are now closer to finding a cure for all SCD patients.
This month, we celebrate the progress made in treating Americans suffering from SCD and renew our commitment to end this disease.
#SCDHopeWins! The Sickle Cell Disease Association of America, Inc. (SCDAA) joins the sickle cell community in celebrating National Sickle Cell Awareness Month in September!
We look forward to all of the information that our community will share this month. We also look forward to sharing some wonderful news items from SCDAA throughout this month – new partnerships, new initiatives and new developments. So, stay tuned!
We have developed a hashtag for this year’s National Sickle Cell Awareness Month – #SCDHopeWins!
It is the tireless work that we all do – from advocacy organizations and community-based organizations to the pharmaceutical companies and federal agencies and government – that brings resources, information and hope to the sickle cell community.
We hope you will join us in using this hashtag for this month, and share it with your networks! Let’s see collectively how many social media impressions we can get using his hashtag. Let’s make sure that SCD is not a forgotten disease!
SCDAA Has A New Logo & Mission Statement
SCDAA is pleased to announce our new brand identity and new mission statement during Sickle Cell Awareness Month. We have two different versions that you will begin to see in our communications and marketing materials. Our goal was to create an icon that would reflect inclusiveness, community and support. With the sickle shapes surrounding individuals living with sickle cell disease and sickle cell trait, the circular shape in turn embraces and supports the the sickle cell community.
We also wanted a new modern, clean and concise logo that speaks directly to the mission of SCDAA. Our new mission statement is: To advocate for people affected by sickle cell conditions and empower community-based organizations to maximize quality of life and raise public consciousness while advancing the search for a universal cure.
Articles in the Medical Literature
Pain. 2018 Sep 20. doi: 10.1097/j.pain.0000000000001407. [Epub ahead of print]
Brandow AM1,2,3, Hansen K1,2, Nugent M2,3,4, Pan A2,3,4, Panepinto JA1,2,3, Stucky CL2,5.
Abstract
Sickle cell disease (SCD) pain associates with cold temperature and touch. Patients and murine models with SCD have baseline thermal and mechanical pain. In SCD mice, the baseline hypersensitivity is exacerbated by experimental vaso-occlusive crises. We hypothesized that SCD patients will similarly experience increased hypersensitivity to thermal and mechanical stimuli during acute painful events compared to baseline health. We conducted a prospective study of 24 SCD patients ages 7-19 yrs. Patients underwent quantitative sensory testing to thermal (cold/heat) and mechanical stimuli on the thenar eminence of the non-dominant hand (glabrous skin) and the lateral dorsum of the foot (hairy skin) during baseline health and within 48 hrs of hospitalization for acute pain. Primary outcomes were changes in: 1) Cold Pain Threshold (°C), 2) Heat Pain Threshold (°C) and 3) Mechanical Pain Threshold (g). Median age was 10.5 (IQR 9-14.8) yrs, 67% were female and 92% were on hydroxyurea. SCD patients had increased cold pain sensitivity in the hand during hospitalization compared to baseline [25.2°C (IQR 18.4-27.5°C) vs. 21.3°C (IQR 4.9-26.2°C); p=0.011] and increased mechanical pain sensitivity in the foot during hospitalization [0.32g (IQR 0.09-1.1g) vs. 1.7g (IQR 0.4-8.3g); p=0.003]. There were no differences in heat pain sensitivity. The increased cold (p=0.02) and mechanical (p=0.0016) pain sensitivity during hospitalization persisted after adjusting for age, gender, hydroxyurea use, opioid consumption and numeric pain score. Thus, cold and mechanical pain is significantly worse during an acute SCD painful event as compared to baseline health in patients with SCD.
PMID: 30247266
F1000Res. 2018 Sep 4;7. pii: F1000 Faculty Rev-1407. doi: 10.12688/f1000research.14589.1. eCollection 2018.
Inusa BPD1, Wale A2, Hassan AA3, Idhate T4, Dogara L5, Ijei I5, Qin Y6, Anie K7,8, Lawson JO9, Hsu L10.
Abstract
The multiple clinical benefits of hydroxycarbamide in sickle cell disease are supported by a large body of evidence. The maximum tolerated dose (MTD) is the regimen recommended by guidelines from a panel of National Heart, Lung, and Blood Institute (NHLBI) experts, but other dosage regimens have been used in babies (BABY-HUG) 9 to 18 months old (20 mg/kg per day) and developing countries such as India (10 mg/kg per day); however, there has been no direct comparison of the efficacy, effectiveness, or cost-effectiveness of these different regimens. The purpose of this review was to investigate the current situation with various hydroxycarbamide regimens with particular relevance to low-middle-income countries. In regard to methodology, a literature review was undertaken by using multiple databases in PubMed and Google and the search terms included sickle cell disease, hydroxyurea, hydroxycarbamide, sickle cell anaemia, low-middle-income countries, Sub-Saharan Africa, and India. Although MTD regimens have been widely used in research, especially within North America, clinical trials elsewhere tend to use fixed-dose regimens. In a survey of haematologists across Europe and Africa, 60% (75% response rate) did not use the MTD regimen for hydroxycarbamide treatment of sickle cell disease. The recommendations are (1) for practical purposes to commence using fixed-dose hydroxycarbamide in line with BABY-HUG recommendations and then (2) to consider or propose a trial comparing MTD escalation with various fixed doses and to include as end points health-related quality of life, haemoglobin F levels, adherence, and cost-effectiveness.
PMCID: PMC6124375 Free PMC Article
PMID: 30228870
Blood. 2018 Sep 11. pii: blood-2018-03-818161. doi: 10.1182/blood-2018-03-818161. [Epub ahead of print]
How I treat the older adult with sickle cell disease.
Abstract
With increasing survival, cumulative complications of sickle cell disease (SCD) which develop insidiously over time, are becoming more apparent and common in older patients, particularly those in their fifth decade and beyond. The older patient is also more likely to develop other age-related non-sickle conditions that interact and add to the disease morbidity. A common misconception is that any symptom in a SCD patient is attributable to their SCD and this may lead to delays in diagnosis and appropriate intervention. We recommend regular comprehensive reviews and monitoring for early signs of organ damage and a low threshold for the use of hydroxyurea and blood transfusions as preventative measures for end organ disease. Treatable co-morbidities and acute deterioration should be managed aggressively. While the primary goal in management of the older adult with SCD is improving anemia and minimizing organ damage, the time has come for us to be more proactive in considering curative therapies previously offered to the younger patient. Curative or experimental interventions should be discussed early, before complications render the patients ineligible for these treatments.
PMID: 30206116
Blood. 2018 Sep 11. pii: blood-2018-03-818195. doi: 10.1182/blood-2018-03-818195. [Epub ahead of print]
How I manage hypoxia in adults with hemoglobinopathies and hemolytic disorders.
Machogu EM1, Machado RF2.
Abstract
Hemoglobinopathies are caused by genetic mutations that result in abnormal hemoglobin molecules that result in hemolytic anemia. Chronic complications involving the lung parenchyma, vasculature and cardiac function in hemoglobinopathies result in impaired gas exchange resulting in tissue hypoxia. Hypoxia is defined as the deficiency in the amount of oxygen reaching the tissues of the body and is prevalent in patients with hemoglobinopathies and its cause is often multifactorial. Chronic hypoxia in hemoglobinopathies is often a sign of disease severity and is associated with increased morbidity and mortality. Therefore, a thorough understanding of the pathophysiology of hypoxia in these disease processes is important in order to appropriately treat the underlying cause and prevent complications. In this article, we discuss management of hypoxia based on three different cases; sickle cell disease, beta-thalassemia and hereditary spherocytosis. These cases are used to review the current understanding of the disease pathophysiology, demonstrate the importance of a thorough clinical history and physical examination, explore diagnostic pathways and review the current management.
PMID: 30206115
Eur J Haematol. 2018 Sep 11. doi: 10.1111/ejh.13173. [Epub ahead of print]
Ballas SK1, Connes P2,3,4; Investigators of the Multicenter Study of Hydroxyurea in Sickle Cell Anemia.
Collaborators: (83)
Hill C, Orringer E, Jones S, Strayhorn D, Rosse W, Phillips G, Peace D, Johnson-Telfair A, Milner P, Kutlar A, Tracy A, Ballas SK, Allen GE, Moshang J, Scott B, Steinberg M, Anderson A, Sabahi V, Pegelow C, Temple D, Case E, Harrell R, Childerie S, Embury S, Schmidt B, Davies D, Koshy M, Talischy-Zahed N, Dorn L, Pendarvis G, McGee M, Telfer M, Davis A, Castro O, Finke H, Perlin E, Siteman J, Gascon P, di Paolo P, Gargiulo S, Eckman J, Bailey JH, Platt A, Waller L, Ramirez G, Knors V, Hernandez S, Rodriguez EM, Wilkes E, Vichinsky E, Claster S, Earles A, Kleman K, McLaughlin K, Swerdlow P, Smith W, Maddox B, Usry L, Brenner A, Williams K, O’Brien R, Genther K, Shurin S, Berman B, Chiarucci K, Keverline L, Olivieri N, Shaw D, Lewis N, Bridges K, Tynan B, Winograd C, Bellevue R, Dosik H, Sheikhai M, Ryans P, Souffrant H, Prchal J, Braddock J, McArdle T, Carlos T, Schmotzer A, Gardner D.
Abstract
OBJECTIVE:
Determine the effect of foetal haemoglobin (HbF) and α-thalassaemia on red blood cell (RBC) deformability of patients with sickle cell anaemia (SCA) with and without hydroxyurea (HU).
METHODS:
Adult patients were enrolled in the Sickle Cell Program of the Cardeza Foundation (Thomas Jefferson University) and were followed-up prospectively during the period in which the Multicenter Study of Hydroxyurea (MSH) in patients with SCA was conducted. Ninety-one patients did not receive HU, 20 patients were enrolled in MSH and 10 patients were enrolled in an open label study of HU in SCA. Of the 20 patients enrolled in MSH, 11 took HU and 9 took placebo. Control group included 113 normal individuals. Red blood cell deformability index (DI) was measured by ektacytometry.
RESULTS:
Patients with SCA taking HU (n=21) had higher DI than those taking placebo (n=9) or who were not taking this therapy (n=91). In patients without therapy, those with α-thalassaemia (n=31) had higher DI than those without. We showed a significant positive correlation between the level of HbF and DI. SCA patients without α-thalassaemia and HbF less than 10% (n=48) had lower DI than patients with α-thalassaemia and HbF < 10% (n=23) and patients with (n=8) or without α-thalassaemia but with HbF > 10% (n=12). DI measured in patients without α-thalassaemia and HbF > 10% was higher than in the three other subgroups.
CONCLUSION:
Elevated levels of HbF with or without HU and α-thalassemia improve sickle RBC rheology, which, in turn, improve the clinical picture of SCA. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
PMID: 30204261
J Pediatr Health Care. 2018 Sep – Oct;32(5):485-489. doi: 10.1016/j.pedhc.2018.04.018. Epub 2018 Jul 4.
Comprehensive Infant Clinic for Sickle Cell Disease: Outcomes and Parental Perspective.
Martin BM, Thaniel LN, Speller-Brown BJ, Darbari DS.
Abstract
INTRODUCTION:
Comprehensive care for children with sickle cell disease (SCD) includes penicillin prophylaxis, pneumococcal immunization, hydroxyurea therapy, and transcranial Doppler screening for stroke prevention. Along with caregiver education, these strategies have been shown to be effective in reducing early morbidity and mortality in this population. The subspecialty Infant Sickle Cell Clinic was initiated to improve access, education, patient outcomes, and family satisfaction.
METHOD:
Telephone surveys were conducted with parents to assess satisfaction with the Infant Sickle Cell Clinic, compliance with guidelines, and comfort level with managing their child’s SCD.
RESULTS:
This quality improvement project reported high levels of parent satisfaction and improved outcomes with the proposed approach but also presents areas for improvement.
DISCUSSION:
Our report presents a unique model of providing care to families with infants newly diagnosed with SCD. The group format serves as a useful model to allow families an interactive educational session with guest speakers.
Copyright © 2018 National Association of Pediatric Nurse Practitioners. Published by Elsevier Inc. All rights reserved.
PMID: 30180940
Sickle Cell Conferences and Events
U.S. Food and Drug Administration (FDA) and American Society of Hematology (ASH) will co-host the Sickle Cell Disease (SCD) Clinical Endpoints Workshop on October 17-18, 2018 in Rockville, MD
This one-time public Workshop aims to identify opportunities to bring uniformity and standards to existing SCD endpoints, identify gaps, and propose development of new endpoints as a focus for future research.
The workshop will include seven panels on the following topics:
- Patient reported outcomes (PROs)
- Pain (non-PROs)
- Brain
- End organ considerations
- Biomarkers
- Endpoints related to curative therapies, including bone marrow transplantation, gene therapy, gene editing, and gene switching
- Considerations of endpoints for low-resource settings
For more information about the Workshop, and to register, click here. For those unable to attend, ASH will provide a live webcast of this Workshop. Further information regarding the webcast will be made available closer to the workshop date. We encourage you to share information about the program with your colleagues.
This workshop is made possible through generous support from the Doris Duke Charitable Foundation as well as support from numerous donors who contributed to the ASH Foundation’s Sickle Cell Disease Initiative Fund.
2018 Sickle Cell in Focus October 22-23, 2018
National Institutes of Health
Natcher Conference Center
Bethesda, MD 20892
Click here for event details and to register!
To view the agenda click here.
46TH ANNUAL Sickle Cell Disease Association NATIONAL CONVENTION
Celebrating the Diversity Within the Sickle Cell Community: Commitment, Innovation, and Practice
With over 600 researchers, physicians, nurses, social workers, individuals living with SCD & SCT in attendance, last year’s year’s convention was a major success and our largest to date. We are excited to unite again with you at the 46th Annual National Convention in Baltimore, MD on October 10-13, 2018 https://www.sicklecelldisease.org/2017/03/07/46th-annual-national-convention/
The 4th Annual Sickle Cell Disease Symposium for Carolinas Healthcare System
Atrium Health will be held on Saturday, October 27, 2018 at the Speedway Club in Charlotte, NC. The theme this year is: “4th Annual SCD Symposium: Racing to Improve the Access to Care & Outcomes for SCD”.
2018 (Re) imagining Health: Sickle Cell Anemia & Thalassaemia: An International Biomedical-Sociocultural Conference
November 16 – 17, 2018
Edmonton Clinic Health Academy, University of Alberta Edmonton, Alberta, Canada
This event will join our community of physicians, surgeons, researchers, medical practitioners and patients with a deep understanding and commitment to finding the cure for Sickle Cell Anemia.
We aim to bring together multiple voices to support and build inclusive and equitable teaching and learning environments, while increasing knowledge of the continued effects of the Sickle Cell Anemia trait. The Sickle Cell Foundation of Alberta is proud to announce the following expert speakers
Dr. Lakiea Bailey, of Georgia, USA
Dr. Carl James, of Toronto, ON
Dr. Emily Meier of Indiana, USA
Dr. Greg Guilcher of Calgary, AB
Dr. Santosh Saraf of Illinois, USA
Dr. Courtney Fitzhugh of Maryland, USA
REGISTRATION – Conference registration is now open. A variety of registration categories are available for the conference. Please see the fee details below or register online here. https://ourscfa.org/conference/
More information can be found on the conference website
www.ourscfa.org/conference Contact us at SCFA@buksa.com
