Accessible Search Form           Advanced Search

Skip left side navigation and go to content


Critical Resources for Gene Therapy in Heart, Lung, and Blood Diseases

Executive Summary

The National Heart, Lung, and Blood Institute convened a Working Group of investigators on June 1, 2005, in St. Louis, Missouri, to gain input on the critical resources needed to successfully translate gene therapy for heart, lung, and blood diseases into clinical practice. The Working Group (WG) members focused on five major topics, as discussed below.


The gaps in our knowledge, inability to screen and diagnose cardiomyopathies in children, and inadequate treatments for children with cardiomyopathies led to the following recommendations:

1. Producing GMP Vectors and Conducting Preclinical Pharmacology/Toxicology Studies

The WG emphasized the importance of developing new vectors and improving gene delivery methods, as well as developing suitable, preclinical, animal models of disease for proof-of-concept studies. Vectors that can efficiently transduce differentiated cell types, delivery systems that permit homogenous distribution of the vector to target cell types, and good animal model systems are all needed. Though gene transfer is a prerequisite for many clinical applications of gene therapy, obtaining efficient transfer to different organs in a system-specific manner has been difficult to achieve, both in vivo and ex vivo. Even when vectors are efficient, transduction of key cell types within the target organs may still remain limited.

2. Funding Phase I and Phase II Gene Therapy Trials

Because of extensive regulatory hurdles, it is difficult, if not impossible, to accurately predict the cost and duration of clinical gene therapy studies. Traditional funding mechanisms are generally too inflexible, and a compartmentalized approach that uses different funding mechanisms for different stages--development, toxicology/production, clinical trials, and so on--is cumbersome and inefficient. Once basic scientific work has progressed to trial readiness, an overall funding mechanism and realistic timeframe should be developed. Trials should be viewed in their entirety, with support provided in stages, as predetermined milestones are met. Funding for gene therapy trials must also include the costs of oversight and compliance.

Ideally, the National Heart, Lung, and Blood Institute (NHLBI) would support Phase I and Phase II trials, which private industry would then further augment to bring products to licensure. Although this has worked successfully for developing conventional drugs, it has not been successful for gene therapies. Academic gene therapy investigators have little incentive to conduct the more complex and expensive trials that would lead to licensure, and private industry may have little interest in treating orphan disorders for which gene therapy may be most efficacious.

3. Patient Recruitment

Recruitment and enrollment for gene therapy trials have proven to be difficult. The WG recognized that, although large-scale trials funded by industry have had fewer problems, NIH-funded trials have been less successful due to factors such as: (a) highly restrictive inclusion and exclusion criteria, (b) availability of more conventional alternative treatments for certain diseases, and (c) the impracticality of involving multiple centers in studies with very complex protocols.

4. Regulatory Processes

One of the major challenges faced by investigators in gene therapy is the complex regulatory process. Planning and executing a gene therapy trial are extremely labor- intensive activities. The regulatory processes involve not only the Food and Drug Administration, but also institutional oversight groups (such as IBCs and IRBs) with varying capabilities, the NIH Recombinant Advisory Committee, peer review groups, and the NHLBI Data and Safety Monitoring Board. Satisfying the requirements of these entities, each of which is individually capable of preventing a study from being conducted, represents a veritable gauntlet for investigators. Streamlining redundancies in this regulatory process could greatly facilitate clinical gene transfer research.

5. Opportunities for Joint Public/Private Partnerships

The potential targets of gene therapy range from rare diseases to the more common diseases/disorders that affect millions of Americans. The incentives for encouraging gene therapy research in academia are not necessarily the same as in the for-profit sector. Finding ways to foster advancement of the entire field of gene therapy, to smoothly transition work done in academia to the private sector, and to make the entire process attractive to both entities are key. The NIH can play a pivotal role in shepherding a viable product through early development in the academic arena to marketability by the private sector. By facilitating an integrative approach to product development, the NIH could speed advances in the field. Public/private partnerships may be possible, however, only if oversight and funding mechanisms are modified.


The WG envisions an NHLBI program that would support clinical, gene therapy, Phase I and Phase II trials by providing the resources needed, such as GMP vector production, preclinical vector production, regulatory affairs support, and pharmacology/toxicology studies. This program would attempt to incorporate the majority of the specific recommendations that the WG made as follows:

  • Provide support for GMP vectors and for preclinical pharmacology/toxicology studies to investigators with NHLBI-approved clinical translational trials.
  • Provide support for trials that involve multiple sites in order to improve patient recruitment.
  • Continue to provide NIH support for "teams" of basic and clinical researchers (through grant mechanisms such as P01s and SCCORs), who are able to assemble the multiple components required for clinical gene therapy studies.
  • Harmonize the regulatory requirements at the local and federal levels.
  • Support clinical and regulatory affairs groups at academic institutions.
  • Encourage representation of patient groups on all regulatory and review panels.
  • Organize a Workshop of invited speakers to focus on the opportunities for public/private partnerships.

Publication Plans:

The report will be posted on the NHLBI web site and the Journal of Molecular Therapy.

NHLBI Contact:

Cheryl McDonald, M.D.

Last updated: July 20, 2005

Twitter iconTwitterimage of external icon Facebook iconFacebookimage of external icon YouTube iconYouTubeimage of external icon Google+ iconGoogle+image of external icon