The Vector

Volume 8, Issue 7: July 2019


Editorial Team

Melvin Rincon, MD, PhD – Editor, The Vector
Edith Pfister, PhD – Associate Editor, The Vector

Inside This Issue

Leadership Message
Breaking Through
Society News
Career Center
Public Policy
Industry News

 

 

Leadership Message

ASGCT Opens Policy Summit Registration

In late May 2019, the FDA approved Zolgensma, an AAV-delivered gene therapy designed to halt spinal muscular atrophy (SMA), for clinical use in the United States. This incredible milestone was long expected from the scientific community and our own membership ranks, and all involved deserve the immense congratulations and outpouring of support they’ve received.

ASGCT has done a wonderful job to promote the scientific work of our members over the past 22 years—I believe we’re the best in the world at profiling new science, supporting upcoming investigators, and sharing new discoveries. But there has long been a gap in our field in one of the most important places: Washington, D.C.

Sometime early last year, the ASGCT board of directors and staff started planning to fill that gap by educating stakeholders, advocating for our members, and proposing solutions for those on Capitol Hill as part of a second annual event, opposite the Annual Meeting on the calendar.

The Society expanded the event into what we now call the ASGCT Policy Summit after the success of last year’s initial summit, and I’m excited to announce registration for the 2019 Policy Summit is now open!

Now expanded from one day to three, the Policy Summit will cover legislative, regulatory, and bioethical content from November 4 – 6 at The Westin City Center in Washington, D.C. Unlike the Annual Meeting, we’re offering daily registration for stakeholders to best tailor their experience to their expertise. Attendance for each day is limited to 350 people, however, so I encourage any interested members to act quickly on their registration. The daily focuses are as follows:

ASGCT leadership is thrilled to see the interest in advocating for gene and cell therapy from our members and look forward to seeing the Policy Summit grow for years to come. I hope many of you will be able to join us in Washington, D.C. this fall.

Best,
Guangping Gao, Ph.D.

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Breaking Through


An Endogenous Anti-aging Factor, Sonic Hedgehog, Suppresses Endometrial Stem Cell Aging through SERPINB2

Ara Cho, Se-Ra Park, Soo-Rim Kim, Seungyoon Nam, Soyi Lim, Chan Hum Park, Hwa-Yong Lee, In-Sun Hong

DOI: https://doi.org/10.1016/j.ymthe.2019.04.019

Summary by Edith Pfister, Ph.D.

As I was browsing the pages of Molecular Therapy this month for new papers, my eyes stopped on an article titled, “An Endogenous Anti-aging Factor, Sonic Hedgehog, Suppresses Endometrial Stem Cell Aging through SERPINB2” by Cho et al.  Like many of my college classmates, I started my family later. I was 34 when I had my first child, sneaking in just under the threshold of what is considered, “advanced maternal age.” I was 37 when I had my second. Fortunately, I never (as far as I know) suffered a pregnancy loss, but a number of my peers were not so lucky. Miscarriage is one of the most common complications of pregnancy occurring in 10-15% of known pregnancies. The risk of miscarriage increases with age, and while we did not often discuss the subject directly, discussions of how old we were and when we were planning on having children were common for a time.

The endometrium has amazing regenerative capacity, undergoing monthly cycles of growth and differentiation throughout the reproductive years. This ability to regenerate and repair month after month relies on endometrial stem cells. With age, stem cells, including those residing in the endometrium, lose their ability to renew and differentiate and senesce, which leads to a decrease in regenerative capacity and fertility issues. What, Cho et al. asked, underlies the decline in stem cell function?

Sonic hedgehog (SHH) is a ligand of the hedgehog signaling pathway well known for its role in development. High levels of hedgehog signaling occur in other regenerating tissues, such as hair, skin, teeth, blood and muscle. In the brain, SHH regulates stem cell proliferation (Palma et al, 2005) and protects against oxidative stress (Dai et al, 2011). Cho et al. hypothesized that decreased expression of SHH underlies the loss of regenerative capacity of endometrial stem cells and may contribute to decreased pregnancy and increased miscarriage with age. The authors found that treatment of endometrial cells in vitro with exogenous SHH decreased markers of senescence in response to both serial passaging and oxidative stress. When they compared tissues from 5 week old and 72 week old mice, they found a significant decrease in both SHH mRNA and protein in multiple organs, including the brain, uterus, liver, and kidneys. The authors hypothesized that another gene, SERPINB2, mediates the effect of SHH on endometrial stem cell senescence. To support this hypothesis, they show that SERPINB2 expression increases with age in mice, and in response to replicative and oxidative stress in endometrial stem cells. Exogenous SHH mutes this effect and silencing of SERPINB2, like expression of SHH, reduces markers of senescence and inflammation in response to stress. They suggest a model where age related decreases in SHH signaling result in increased SERPINB2 and reduced regenerative capacity in endometrial stem cells.

So is modulation of SHH a potential treatment for age related declines in fertility? Probably not. Impairment of SHH signaling is associated with diseases of aging, but upregulation of signaling is seen in many cancers. Hedgehog signaling may be the proverbial double-edged sword, but this study provides some interesting clues as to how aging and environmental factors may interact to decrease fertility and increase the risk of miscarriage.

Society News


2019 Policy Summit Registration is Now Open

Daily registration allows Policy Summit attendees to choose the legislative, regulatory, and bioethical content that's most relevant to them, or to register for all three days (November 4 – 6) for a full-scope experience.

Register Today!

 

ASGCT Leads Congressional Briefing on Gene Therapy for Sickle Cell Disease with Sens. Tim Scott and Cory Booker

ASGCT co-hosted a congressional briefing on sickle cell disease (SCD) with Sens. Tim Scott and Cory Booker with additional stakeholder organizations.

See Sen. Scott's Opening Remarks
on the ASGCT Twitter Account

Taking place before a standing-room only audience of nearly 100 congressional staff members and other stakeholders, the briefing addressed progress in gene therapy for sickle cell disease and related policy implications. At the briefing, ASGCT echoed Sen. Scott’s call for use of novel payment models to address the unique, one-time nature of gene therapies—payment over time and outcomes-based payments. 

ASGCT speakers addressed the importance of the additional policies of robust funding to the NIH; appropriating funds for surveillance of SCD authorized by a law passed in December; and reauthorizing the newborn screening program this year. ASGCT researchers Punam Malik, M.D. (Cincinnati Children’s Hospital), Matthew Porteus, M.D., Ph.D. (Stanford University), and David Williams, M.D. (Dana-Farber Cancer Institute, Boston Children’s Hospital, and Harvard University) presented the progress they and their peers have contributed to through a variety of gene therapy and gene editing approaches for SCD.

Download the Full Slide Deck on ASGCT.org

ASGCT to Award $300,000 to Members in 2019

ASGCT will award a $50,000 Career Development Award in each of the following six broad topics. The purpose of these awards is to support independent transformative pilot studies in gene and cell therapy by ASGCT members, particularly those ideas that would be challenging to fund with normal funding mechanisms. ASGCT is interested in helping applicants generate their preliminary data to use in larger proposals (NIH K awards, first-submission R-level funding, etc.) to gain independence. Learn more about the eligibility requirements, application materials, and key deadlines in the Career Development Award Overview and Benefits.

Learn more at ASGCT.org and apply by August 1

Career Center—NEW!

Recruit and connect with top gene and cell therapy job seekers on the ASGCT Job Bank.

Advertising opportunities are also available monthly via the Featured Jobs section and allow recruiting institutions to target the 3,000+ audience of The Vector.

Featured Jobs

Public Policy


House Companion Bill Would Enable Value-Based Purchasing Arrangements

ASGCT sent a letter this week regarding draft legislation to its House sponsors, the four co-chairs of the Health Care Innovation Caucus. The draft bill is aimed at enabling agreements containing value-based payment arrangements, which tie a portion of reimbursement of a drug or therapy to meeting predetermined outcomes. In its comments, the Society supported enabling such payment models for gene and genetically-modified cell therapies. The Society requested clarification, through this type of legislation, on how potential regulatory and legal barriers (anti-kickback statutes and Medicaid Best Price requirements) to value-based payment arrangements would be handled. Additionally, ASGCT recommended bill sponsors consider adding a provision for, or clarifying inclusion of, pay-over-time arrangements for gene therapies, which would distribute upfront costs for one-time treatments over a period of years. ASGCT supports enabling these novel payment models to maximize patient access to these innovative treatments. ASGCT’s support of provisions of the proposed bill does not imply endorsement of any specific gene therapy pricing decisions.

ASGCT Supports Improvements in Medicare Reimbursement for CAR T-Cell Therapy

Last month, ASGCT submitted comments to the Centers for Medicare & Medicaid Services (CMS) on the FY 2020 Inpatient Prospective Payment System proposed rule related to reimbursement mechanisms for CAR T-cell therapy. Currently providers are sustaining substantial financial losses for providing CAR T-cell therapy, which may create a patient access issue. In the rule, CMS proposed increasing the maximum available new technology add-on payment (NTAP) to 65 percent (from the current 50 percent), which may still leave hospitals that utilize a low markup level with losses of over $300,000 per Medicare beneficiary.

In its comments, the Society recommended increasing provider reimbursement levels through further increasing the cap on NTAPs to 100 percent; and utilizing the actual cost for providers to acquire the CAR T-cell product when determining NTAP and outlier payment amounts, regardless of markup practices, to support transparency in charging practices. ASGCT also recommended collecting data on actual acquisition costs of the CAR T-cell product over the next two years to use in accurate setting of a new diagnosis-related group (DRG) for CAR T-cell therapy in 2022. While ASGCT supports reform of outdated Medicare reimbursement mechanisms, comments indicated this position does not imply endorsement of any individual pricing decisions.

Industry News


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2019

ASGCT Policy Summit

November 4 – 6 | Washington D.C.