Tag Archives: CMO Speaks

CMO Speaks: Making ED Care Better for SCD – Progress in 2023

Welcome to CMO Speaks, a blog featuring the voices of SCDAA’s clinical leadership team. This article was written by Dr. Lewis Hsu, SCDAA’s chief medical officer.

The Emergency Department is no one’s favorite place, but unfortunately individuals with sickle cell disease may pay it frequent visits for emergency care. Encountering problems in ED care is distressingly common. During the SCDAA Annual National Convention in October 2023, SCDAA participated in a joint session with the Emergency Department Sickle Cell Care Coalition (EDSC3) entitled “Summit on Emergency Department Sickle Cell Care.”

The special morning session, Frameworks to Improve the Emergency Department Experience for Sickle Cell Disease, focused on existing guidelines and efforts related to dissemination and education of emergency medicine clinicians. The keynote speaker for this morning session was Dr. Aisha Terry, president of the American College of Emergency Physicians. Videos expressing the views of people living with sickle cell disease and those that care for them give further insight into the current state of care delivered in the emergency department.

Other speakers included:

  • Dr. Henry Young: Point-of-Care Tool to guide management of SCD
  • Dr. Paula Tanabe: Statewide standardization of care processes, the North Carolina experience
  • Dr. David Brousseau: Implementation through a research network, the PECARN experience
  • Yvonne Carroll: IASCNAPA sickle cell disease bootcamp for nurses

Major Takeaways on ED Care from the Convention

  1. Dr. Paula Tanabe made presentations that included implementation tips for Individualized Pain Plans (IPP) to help ED doctors and nurses to see that the IPP can help speed up their workflow. She suggested that providers put the IPP in the health record where a Patient Portal can access it. One individual reportedly showed their IPP to a new ED when traveling out of state, and that ED acted upon the IPP as credible information.
  2. SCDAA is partnering with MedicAlert to store IPPs online and provide patients with a bracelet/wallet card with a QR code that links to their information. We hope that the MedicAlert imprint will make the IPP credible.
  3. The ACEP Point-of-Care Tool for sickle cell (website and mobile app) built into their algorithm for sickle cell acute management that dosing of pain meds should be guided by IPP as first choice, weight-based dosing as second choice.
  4. A new calculator for sickle cell experts to create IPP dosing in the ED based upon the individual’s chronic opioid intake was created by Dr. Paula Tanabe and Dr. Patricia Kavanagh. The tool was validated in a clinical trial COMPARE-VOE. The Excel calculator and instructions are posted for health care providers to use at the National Alliance of Sickle Cell Centers website.

Lewis Hsu, MD, PhD, is a pediatric hematologist who serves as director of the Sickle Cell Center and professor of pediatrics for the University of Illinois at Chicago. He has conducted sickle cell research, published over 100 publications and co-authored “Hope and Destiny: The Patient and Parent’s Guide to Sickle Cell Disease and Sickle Cell Trait.” He currently serves as the SCDAA Chief Medical Officer. 

CMO Speaks: Gene Therapy for SCD (Part 2)

Welcome to CMO Speaks, a blog featuring the voices of SCDAA’s clinical leadership team. This is part two of a three-part series on gene therapy for sickle cell disease. Part two was written by Dr. Lewis Hsu.

What comes up for you when you hear the words “gene therapy?” If it makes you feel overwhelmed, skeptical and/or confused, you’re not alone. There are a lot of misconceptions about gene therapy, and it can be hard to understand why it’s so important. Get some answers to frequently asked questions about gene therapy below!

Q: Is gene therapy for sickle cell disease a surgery? How long does it take?
A: It is not a surgery, more of a process. It can take a while to complete. We advise people considering gene therapy to estimate that it will be like a full-time job for the first six months and continue to be very time intensive for one to two years afterward.

Q: Where can I get information about gene therapy for sickle cell disease?
A: We encourage you to start with these online resources:

New updates are presented at sickle cell conferences annually. Consider registering for the SCDAA Annual National Convention, the Foundation for Sickle Cell Disease Research’s Annual Sickle Cell Disease Research and Educational Symposium and others.

Q: How do I sign up for gene therapy?

A: There are at least five groups trying to develop gene therapy for SCD. All are currently conducting clinical research studies. The specialized team that does gene therapy overlaps with the team preforming bone marrow transplants. You can search for research opportunities using SCDAA’s Clinical Trial Finder or by visiting ClinicalTrials.gov. Signing up for gene therapy requires a lot of discussion and deep thought by the patient and their whole family. Read this statement from SCDAA’s Medical and Research Advisory Committee to learn more about what it means to participate in a clinical trial.

Q:  What connects sickle cell disease to gene therapy?

A:  Sickle cell disease is inherited, so if a person’s bone marrow stem cells have the genes for sickle hemoglobin, the red blood cells will cause sickle cell disease (SCD). Medicines can make SCD symptoms milder, but they cannot stop a person’s body from producing sickle hemoglobin. One way to stop the process and “cure” the disease would be through a stem cell transplant. However, this involves finding a donor – which can be tricky. The ultimate way to cure a genetic disease like sickle cell is by adjusting the genes so they do not make sickle hemoglobin in the first place – that is what we mean when we talk about gene therapy. It is a long-term cure that doesn’t require a donor. There are several techniques to do gene therapy.

Q:  What was the recent news about gene therapy and sickle cell disease?

A:  There was a lot of news in January – March 2023!

  1. The New York Times published this article and National Public Radio reported that gene therapy is a pioneering treatment for sickle cell disease. They highlighted the voices and experiences of advocates from around our community.
  2. Two pharmaceutical companies (bluebird bio and Vertex/CRISPR) announced that they will bring their SCD gene therapy clinical research results to the U.S. Food and Drug Administration (FDA) for possible approval as safe and effective in the first quarter of 2023. In late February, three other groups (Sangamo, Graphite Bio, Intellia) each announced the closure of their SCD gene therapy clinical research studies, apparently as business decisions.
  3. The Third International Summit on Human Genome Editing was held in London on March 6-8, 2023, and a lot of time was devoted to discussing sickle cell disease, including science, ethics and patient perspectives. One perspective is that gene therapy is one of the greatest advancements for sickle cell disease and provides hope for a “universal cure.” Victoria Gray, the first person to be cured of SCD using the CRISPR genome editing technology, was a special featured speaker. She told a powerful story about her life before and after the gene therapy. SCDAA board member Dr. Melissa Creary spoke as someone contemplating gene therapy and shared her concerns about equity and ethics related to the technology.

Q: Is the sickle cell community in favor of gene therapy?

A: Yes, gene therapy potentially could cure anybody with SCD and lead us to a universal cure. However, many important details need to be worked out before we reach that point.

Q: Would this be funded by taxpayer money? Why should a society pay the high cost of gene therapy? Or the high costs of any SCD care?

A: The high upfront cost will have a “return on investment” in the long term. Direct savings will be seen in lower medical costs for the rest of our lifetimes. Indirect economic benefits to society include fewer absences from work for individuals and caregivers, less suffering, more productive taxpayers and less crowded hospitals and emergency departments. We lack actual long-term data, but math models could estimate a “return on investment.”

Q: Does everybody with sickle cell disease want gene therapy?

A: Not yet. Some worry about side effects of gene therapy preparation, including the risks of infertility and unknown risks of leukemia. Others cannot devote the time (a year or more) for the gene therapy process. Some people feel that their current medications are controlling their SCD quite well and don’t feel the need to change their treatment plan. Some have misinformation about the process and might change their decision with better awareness. Some people simply want to “wait and see” about any new medical treatment.

Q: Will health disparities limit access to gene therapy?

A: Inequities stemming from racism, stigma and poverty are a big problem in sickle cell care now. Unless proactive steps change the US health care system, gene therapy will magnify these inequities in the US. The global impacts of gene therapy must be considered as well. Can the vast population with SCD in sub-Saharan Africa and elsewhere get access to gene therapy, or will Americans reap the greatest benefits?

Q: Should all government supported funds for sickle cell disease go to researching gene therapy?

A: It should not be an “all-or-nothing” decision. There can be a “return on investment” for federal and state funding to fulfill the evidence-based standards of care for SCD. Better care for pain in the emergency department, more access to FDA-approved medications for SCD, more comprehensive care centers with staff who are trained in modern guidelines and more awareness of SCD and sickle cell trait are all high priorities for the SCD community. People should not continue to suffer substandard SCD care while waiting for gene therapy to be developed.

If I have 25 seconds to comment on sickle cell disease gene therapy:

  1. Gene therapy progress is accelerating in SCD (“hitting the gas”). bluebird bio and Vertex/CRISPR are bringing data to FDA to ask for approval.
  2. The high upfront cost of SCD gene therapy will be worthwhile because of the “return on investment.”
  3. Individuals with SCD should not continue to suffer substandard care while waiting for gene therapy to be developed.

https://youtu.be/DqETbmgFdto

 

Lewis Hsu, MD, PhD, is a pediatric hematologist who serves as director of the Sickle Cell Center and professor of pediatrics for the University of Illinois at Chicago. He has conducted sickle cell research, published over 50 peer-reviewed papers and co-authored “Hope and Destiny: The Patient and Parent’s Guide to Sickle Cell Disease and Sickle Cell Trait.” He currently serves as the SCDAA Chief Medical Officer.  

CMO Speaks: Gene Therapy for SCD (Part 1)

CMO Speaks is a blog featuring the voices of SCDAA’s clinical leadership team. Part 1 of our Gene Therapy series was written by Dr. Lewis Hsu and Dr. Sri Lakshmi Jamalapur.

How can you cure an inherited disease like sickle cell disease? One way would be to develop some extremely effective medications that would alleviate all the symptoms. Another would be to transplant stem cells that produce red blood cells. But the ultimate way to cure genetic disease is with gene therapy.

Gene therapy is a relatively new treatment for sickle cell warriors. Researchers began conducting experimental studies (clinical research) in people about seven years ago. At first, the only approach to this treatment was a process called “gene addition” developed by the Boston-based pharmaceutical company bluebird bio. Soon, several other groups joined with other approaches for gene therapy. By early 2022, there were six competing organizations enrolling in gene therapy clinical research. They are listed in the table below.

There has been a lot of news recently regarding gene therapy. Earlier this year, The New York Times published this article about gene therapy and sickle cell disease, which highlighted the voices and experiences of advocates from around our community and brought renewed attention to this pioneering treatment. Two pharmaceutical groups say that they will bring their gene therapy clinical research results to the U.S. Food and Drug Administration (FDA) for possible approval as safe and effective in the first quarter of 2023 (highlighted green in the table).

At the same time, in late February, three other groups announced that they are closing their gene therapy clinical research studies (highlighted yellow in the table). Some people worry that seeing companies end their gene therapy studies is not good news for sickle cell disease. However, another way to look at these announcements is that the most fruitful studies are heading toward possible FDA approval. Less productive clinical research efforts are cutting their losses and being pruned away.

It’s like a gardener doing work in a little garden to keep the plants that are bearing fruit (the two groups that will bring their results to U.S. FDA) alive but removing those plants that have stopped growing (the groups that are closing their gene therapy clinical research). The wisdom of pruning down the less productive activity is recognized by many proverbs, including “if you run after two hares, you will catch neither,” or “have too many irons in the fire,” or “he who tries to sit on two chairs will end up sitting on neither,” or John 15:1 in the Bible. Drop-out studies are part of the healthy competitive process of research and investment.

Table 1: Current and upcoming studies of gene therapy in SCD. (adapted from Kanter and Falcon 2021; Hsu and Jamalapur 2022) N/A – not applicable; LVV – lentiviral vector; HbAT87Q – Hb with a single mutation conferring most of the antisickling effect of γ-globin; βAS3 – an antisickling β-globin containing 3 amino acid substitutions in the wild-type HBB; HbFG16D – modified HbF that increases affinity to α-globin to outcompete sickle mutated β-globin; AAV6 – Adeno-Associated Virus serotype 6.

Outside of gene therapy studies, promising sickle cell progress is everywhere. Researchers are developing innovative medications and studying stem cell transplants that could make a world of difference to warriors who are unable or unwilling to undergo gene therapy in the future. The clinical research process is fine-tuned to determine which treatments are safe and effective. Sickle cell warriors are encouraged to help push this research forward by participating in clinical trials.

Lewis Hsu, MD, PhD, is a pediatric hematologist who serves as director of the Sickle Cell Center and professor of pediatrics for the University of Illinois at Chicago. He has conducted sickle cell research, published over 50 peer-reviewed papers and co-authored “Hope and Destiny: The Patient and Parent’s Guide to Sickle Cell Disease and Sickle Cell Trait.” He currently serves as the SCDAA Chief Medical Officer.

Sri Lakshmi Jamalapur, MD, is a pediatric hematologist and the new leader for the Pediatric Sickle Cell Center at Children’s Hospital of Michigan in Detroit. She has collaborated with Dr. Hsu on health education and sickle cell advocacy since 2019.  

CMO Speaks: Fertility Care and SCD

CMO Speaks is a blog featuring the voices of SCDAA’s clinical leadership team. The below article was written by Dr. Lewis Hsu, SCDAA chief medical officer, with input from Dr. Lydia Pecker.

NPR recently produced this segment with sickle cell warrior and advocate Teonna Woolford on fertility care and SCD. This is an underdiscussed topic and an important aspect of sickle cell care. We congratulate Teonna and the Sickle Cell Reproductive Health Education Directive (SC RED) for getting this message out, and we are grateful for the attention from NPR. In light of this discussion, we would like to reinforce a few points about reproductive health and SCD:

  1. Even without a transplant or gene therapy, sickle cell disease can damage patients’ bodies in ways that can affect their ability to have children. We agree with the statements by Drs. Lydia Pecker and Leena Nahata in this NPR report.
  2. Currently, insurance coverage for fertility preservation is highly variable and differs from state to state. We agree with statements in this NPR report by Dr. Irene Su about the vagueness of these policies. This is a sickle cell advocacy opportunity to get coverage in more states. SCDAA praises the efforts of SC RED and the Alliance for Fertility Preservation as allies in fighting for coverage. However, just as the NPR report described for intrauterine insemination, there are high costs and many other barriers of access to these procedures. Shared decision-making should be the model for information, choices and policies.
  3. SCDAA agrees wholeheartedly with the statements in this NPR report regarding funding disparities and the lack of information dissemination about sickle cell disease. The NASEM 2020 Report has much more information about action steps to take.

    Go deeper – What is not brought out in this NPR report

    1. Sickle cell disease is an inherited condition. Another aspect of reproductive decision-making for individuals with SCD is understanding the risks of having a child who also has sickle cell disease (more about family planning in this infographic from SC RED). Having a child with sickle cell disease is not a mistake, but it should not be a surprise for lack of information. Tests are available to know whether the mate has the sickle gene or another hemoglobin variant. Tests are available for prenatal diagnosis. Fertility centers also can do preimplantation genetic diagnosis and embryo selection to choose an embryo without sickle cell disease.
    2. For individuals with sickle cell, choosing to have children also means gathering a support system so that they can be a caregiver for a child when they themselves have sickle cell problems. (Currently, the mother of one of my patients cannot be at the bedside for her child with sickle acute chest syndrome because she is hospitalized herself for sickle cell pain.)
    3. Making reproductive decisions would be best done in the format of “shared decision-making.” These are complicated decisions that depend on individual situations and individual values. Individuals with sickle cell disease should try to be well-informed. Try to explain your values and reasons to your health care provider(s), and ask questions until you have a solid understanding. Please be aware that some things are not certain in medicine and in reproduction and can only be described as chances and risks.

    Helpful links and resources

    Lewis Hsu, MD, PhD, is a pediatric hematologist who serves as director of the Sickle Cell Center and professor of pediatrics for the University of Illinois at Chicago. He has conducted sickle cell research, published over 50 peer-reviewed papers and co-authored “Hope and Destiny: The Patient and Parent’s Guide to Sickle Cell Disease and Sickle Cell Trait.” He currently serves as the SCDAA Chief Medical Officer.