CCM–CARE Act of 2023

II 118TH CONGRESS 1ST SESSION S. 543 To increase research, education, and treatment for cerebral cavernous malformations. IN THE SENATE OF THE UNITED STATES FEBRUARY 28, 2023 Mr. LUJA´N (for himself and Mr. HEINRICH) introduced the following bill; which was read twice and referred to the Committee on Health, Edu- cation, Labor, and Pensions A BILL To increase research, education, and treatment for cerebral cavernous malformations. Be it enacted by the Senate and House of Representa- 1 tives of the United States of America in Congress assembled, 2 SECTION 1. SHORT TITLE. 3 This Act may be cited as the ‘‘Cerebral Cavernous 4 Malformations Clinical Awareness, Research, and Edu- 5 cation Act of 2023’’ or the ‘‘CCM–CARE Act of 2023’’. 6 SEC. 2. FINDINGS. 7 Congress finds as follows: 8 (1) Cerebral cavernous malformations (referred 9 to in this section as ‘‘CCM’’), also known as cav- 10 VerDate Sep 11 2014 01:12 Mar 08, 2023 Jkt 039200 PO 00000 Frm 00001 Fmt 6652 Sfmt 6201 E:\BILLS\S543.IS S543 kjohnson on DSK79L0C42PROD with BILLS 2 •S 543 IS ernous angioma, or cavernoma, is a devastating 1 blood vessel disease characterized by vascular lesions 2 that develop and grow within the brain and spinal 3 cord. 4 (2) Detection of CCM lesions is achieved 5 through costly and specialized medical imaging tech- 6 niques, often not accessible or convenient to patients 7 who need them. 8 (3) While CCM is a common type of vascular 9 anomaly, many individuals are not aware they have 10 the disease until the onset of serious clinical symp- 11 toms. CCM is often inherited unknowingly. 12 (4) CCM affects an estimated 600,000 people 13 in the United States, although fewer than 200,000 14 are accurately diagnosed. 15 (5) Individuals diagnosed with CCM may expe- 16 rience neurological deficits, seizure, stroke, or sud- 17 den death. 18 (6) Due to limited research, there is currently 19 no treatment for CCM other than brain and spinal 20 surgery, and only for certain patients. 21 (7) There is also a shortage of trained physi- 22 cians to provide skilled and timely diagnosis and ap- 23 propriate treatment for CCM. 24 VerDate Sep 11 2014 01:12 Mar 08, 2023 Jkt 039200 PO 00000 Frm 00002 Fmt 6652 Sfmt 6201 E:\BILLS\S543.IS S543 kjohnson on DSK79L0C42PROD with BILLS 3 •S 543 IS (8) While the hereditary form of CCM may 1 occur among any ethnicity, the presence of a muta- 2 tion called the ‘‘common Hispanic mutation’’, has 3 passed through 14 or more generations of American 4 descendants from the original Spanish settlers of the 5 Southwest in the 1590s. New Mexico has the highest 6 population density of CCM in the world; Texas, Ari- 7 zona, and Colorado also have high rates of CCM due 8 to the common Hispanic mutation. 9 (9) A second mutation (CCM2 Common Dele- 10 tion) originating in the Southeastern United States 11 before 1800 has increased rates of the illness in 12 South Carolina, Georgia, Florida, Alabama, Mis- 13 sissippi, Louisiana, Texas, Oklahoma, Kentucky, 14 Kansas, and northern California. 15 SEC. 3. EXPANSION AND COORDINATION OF ACTIVITIES OF 16 NATIONAL INSTITUTES OF HEALTH WITH RE- 17 SPECT TO CEREBRAL CAVERNOUS MAL- 18 FORMATIONS RESEARCH. 19 Part B of title IV of the Public Health Service Act 20 (42 U.S.C. 284 et seq.) is amended by adding at the end 21 the following: 22 VerDate Sep 11 2014 01:12 Mar 08, 2023 Jkt 039200 PO 00000 Frm 00003 Fmt 6652 Sfmt 6201 E:\BILLS\S543.IS S543 kjohnson on DSK79L0C42PROD with BILLS 4 •S 543 IS ‘‘SEC. 409K. CEREBRAL CAVERNOUS MALFORMATIONS RE- 1 SEARCH ACTIVITIES. 2 ‘‘(a) EXPANSION AND COORDINATION OF ACTIVI- 3 TIES.—The Director of NIH, in coordination with the di- 4 rectors of the National Institute of Neurological Disorders 5 and Stroke, the National Center for Advancing 6 Translational Sciences, the National Heart, Lung, and 7 Blood Institute, and other national research institutes, as 8 appropriate, for the purpose of conducting research and 9 related activities concerning cerebral cavernous malforma- 10 tions (referred to in this section as ‘CCM’)— 11 ‘‘(1) shall strengthen and coordinate efforts of 12 the National Institutes of Health; and 13 ‘‘(2) may award grants and cooperative agree- 14 ments to public or nonprofit private entities (includ- 15 ing State health departments, political subdivisions 16 of States, universities, and other medical or edu- 17 cational entities). 18 ‘‘(b) ACTIVITIES.—The research and related activi- 19 ties described in subsection (a) shall include the following: 20 ‘‘(1) CLINICAL, TRANSLATIONAL, AND BASIC 21 RESEARCH.—The Director of NIH shall conduct or 22 support, through funding opportunity announce- 23 ments, grants, or cooperative agreements, basic, clin- 24 ical, and translational research on CCM, including 25 research on— 26 VerDate Sep 11 2014 01:12 Mar 08, 2023 Jkt 039200 PO 00000 Frm 00004 Fmt 6652 Sfmt 6201 E:\BILLS\S543.IS S543 kjohnson on DSK79L0C42PROD with BILLS 5 •S 543 IS ‘‘(A) the identification and development of 1 affordable imaging, plasma, and urine biomark- 2 ers that fulfill the requirement of the Food and 3 Drug Administration for biomarker qualifica- 4 tion as proper measures of CCM pathogenic bi- 5 ology, including diagnosis, response to clinical 6 intervention, or prediction of adverse clinical 7 events; 8 ‘‘(B) pre-clinical trials of promising CCM 9 drug treatment candidates; 10 ‘‘(C) novel biomedical and pharmacological 11 interventions designed to target existing lesions 12 to reduce their size and clinical activity; 13 ‘‘(D) clinical research related to 14 repurposing currently approved drugs for appli- 15 cation for CCM treatment; 16 ‘‘(E) development of new non-pharma- 17 cological treatment approaches, such as focused 18 ultrasound, and targeted treatment delivery 19 technology; 20 ‘‘(F) the gut-brain axis and the effects of 21 microbiome composition on clinical 22 symptomology; 23 ‘‘(G) the microbiome as a therapeutic tar- 24 get for CCM treatment; 25 VerDate Sep 11 2014 01:12 Mar 08, 2023 Jkt 039200 PO 00000 Frm 00005 Fmt 6652 Sfmt 6201 E:\BILLS\S543.IS S543 kjohnson on DSK79L0C42PROD with BILLS 6 •S 543 IS ‘‘(H) research related to gene therapy as a 1 treatment for familial CCM; 2 ‘‘(I) research related to RNA-based thera- 3 pies; 4 ‘‘(J) research related to the mechanistic 5 overlap between CCM and other disorders, in- 6 cluding vascular disorders and cancer; 7 ‘‘(K) research related to improving and 8 measuring the quality of life for individuals 9 with CCM and their families; 10 ‘‘(L) contributions of genetic variation to 11 clinical presentation as precision medicine tar- 12 gets for therapy; 13 ‘‘(M) clinical training programs aimed at 14 increasing the number of scientists and clini- 15 cians who are trained to treat patients and 16 carry out the research described in this para- 17 graph; 18 ‘‘(N) proteomic, pharmacological, and cell 19 biological analysis of CCM molecules; 20 ‘‘(O) biological mechanisms for lesion gen- 21 esis, development, and maturation; 22 ‘‘(P) biological mechanisms for lesion 23 bleeding and symptomology; 24 VerDate Sep 11 2014 01:12 Mar 08, 2023 Jkt 039200 PO 00000 Frm 00006 Fmt 6652 Sfmt 6201 E:\BILLS\S543.IS S543 kjohnson on DSK79L0C42PROD with BILLS 7 •S 543 IS ‘‘(Q) novel biomedical and pharmacological 1 interventions designed to inhibit new lesion de- 2 velopment, lesion growth, and lesion bleeding; 3 and 4 ‘‘(R) continued research related to under- 5 standing better the natural history and clinical 6 variation associated with CCM, particularly as 7 it relates to the development of drug develop- 8 ment tools and clinical outcome assessments. 9 ‘‘(2) FACILITATION OF RESEARCH RESOURCES; 10 CLINICAL TRIAL PREPAREDNESS.— 11 ‘‘(A) IN GENERAL.—The Director of NIH 12 shall award grants and contracts to public or 13 nonprofit private entities to fund all or part of 14 the cost of planning, establishing, and providing 15 basic operating support for a network of CCM 16 Clinical Research Centers, including Coordi- 17 nating and Participating centers regarding re- 18 search on various forms of CCM. 19 ‘‘(B) CLINICAL AND RESEARCH COORDI- 20 NATING CENTERS.— 21 ‘‘(i) IN GENERAL.—The Director of 22 NIH shall build upon the network created 23 by the U01 Clinical Trial Readiness Re- 24 search Project to identify and support the 25 VerDate Sep 11 2014 01:12 Mar 08, 2023 Jkt 039200 PO 00000 Frm 00007 Fmt 6652 Sfmt 6201 E:\BILLS\S543.IS S543 kjohnson on DSK79L0C42PROD with BILLS 8 •S 543 IS development of 2 geographically distributed 1 national clinical and research coordinating 2 centers with unique clinical expertise and 3 the potential for coordinating multisite 4 clinical drug trials with respect to CCM, 5 including serving as United States sites in 6 international adaptive trials. 7 ‘‘(ii) DUTIES.—The coordinating cen- 8 ters identified under clause (i) shall pro- 9 vide a model for the participation centers 10 described in paragraph (3), facilitate med- 11 ical research to develop a cure for CCM, 12 and enhance the medical care of individ- 13 uals with CCM nationwide, including by— 14 ‘‘(I) maintaining an institutional 15 infrastructure capable of hosting clin- 16 ical trials, facilitating translational re- 17 search projects, and domestic and 18 international collaborations for clinical 19 trials; 20 ‘‘(II) implementing the programs 21 dedicated to patient education, patient 22 outreach, and awareness developed by 23 the Cerebral Cavernous Malformations 24 VerDate Sep 11 2014 01:12 Mar 08, 2023 Jkt 039200 PO 00000 Frm 00008 Fmt 6652 Sfmt 6201 E:\BILLS\S543.IS S543 kjohnson on DSK79L0C42PROD with BILLS 9 •S 543 IS Consortium under subsection 1 (c)(3)(B); 2 ‘‘(III) developing the capacity to 3 establish and maintain communication 4 with other major CCM research and 5 care institutions internationally for in- 6 formation sharing and coordination of 7 research activities; 8 ‘‘(IV) demonstrating clinical ex- 9 pertise in the management of CCM 10 and appointing a director and support 11 staff, including a trainee and patient 12 representative, for CCM research pro- 13 gramming; 14 ‘‘(V) treating a sufficient number 15 of eligible patients for participation 16 with particular focus on unique sub- 17 populations, such as patients with the 18 common Hispanic mutation, Ash- 19 kenazi Jewish mutation, CCM2 Com- 20 mon Deletion, CCM3 gene mutation 21 carriers, or Black and under- 22 resourced patients; and 23 ‘‘(VI) maintaining a telehealth 24 infrastructure to support and provide 25 VerDate Sep 11 2014 01:12 Mar 08, 2023 Jkt 039200 PO 00000 Frm 00009 Fmt 6652 Sfmt 6201 E:\BILLS\S543.IS S543 kjohnson on DSK79L0C42PROD with BILLS 10 •S 543 IS clinical consultation for remote and 1 underserved communities. 2 ‘‘(3) PARTICIPATION CENTERS.— 3 ‘‘(A) IN GENERAL.—The Director of NIH 4 shall build upon the network created by the 5 U01 Clinical Trial Readiness Research Project 6 to identify and support the development of ap- 7 proximately 6 to 10 clinical and research par- 8 ticipation centers to facilitate medical research 9 to develop a cure for CCM and enhance the 10 medical care of individuals with CCM, in part- 11 nership with the coordinating centers under 12 paragraph (2) and other national and inter- 13 national entities, as appropriate. 14 ‘‘(B) ELIGIBILITY.—To qualify for selec- 15 tion as a participation center under subpara- 16 graph (A), an entity shall— 17 ‘‘(i) at the time of selection— 18 ‘‘(I) be affiliated with an estab- 19 lished research network of the Na- 20 tional Institutes of Health; and 21 ‘‘(II) have the potential to par- 22 ticipate in a multisite clinical drug 23 trial with respect to CCM; 24 ‘‘(ii) demonstrate— 25 VerDate Sep 11 2014 01:12 Mar 08, 2023 Jkt 039200 PO 00000 Frm 00010 Fmt 6652 Sfmt 6201 E:\BILLS\S543.IS S543 kjohnson on DSK79L0C42PROD with BILLS 11 •S 543 IS ‘‘(I) the capacity to maintain 1 communication with other major CCM 2 research and care institutions inter- 3 nationally for information sharing and 4 coordination of research activities, es- 5 pecially through health information 6 technology; and 7 ‘‘(II) clinical expertise in CCM 8 management or complete the CCM 9 clinical training program under sub- 10 section (c)(4); and 11 ‘‘(iii) have a sufficient number of eli- 12 gible patients with CCM. 13 ‘‘(C) DURATION OF SUPPORT.—The Direc- 14 tor of NIH may provide support for participa- 15 tion centers under this section for a period not 16 to exceed 5 years. The Director of NIH may ex- 17 tend the period of support for a center for one 18 or more additional periods, not to exceed an ad- 19 ditional 5 years, if the operations of such center 20 have been reviewed by an appropriate technical 21 and scientific peer review group established by 22 the Director of NIH and if such group has rec- 23 ommended to the Director that such period 24 should be extended. 25 VerDate Sep 11 2014 01:12 Mar 08, 2023 Jkt 039200 PO 00000 Frm 00011 Fmt 6652 Sfmt 6201 E:\BILLS\S543.IS S543 kjohnson on DSK79L0C42PROD with BILLS 12 •S 543 IS ‘‘(c) CEREBRAL CAVERNOUS MALFORMATIONS CON- 1 SORTIUM.— 2 ‘‘(1) IN GENERAL.—The Director of NIH shall 3 build upon the network created by the U01 Clinical 4 Trial Readiness Research Project to convene a Cere- 5 bral Cavernous Malformations Research Consortium 6 (referred to in this section as the ‘consortium’). 7 ‘‘(2) MEMBERSHIP.—The consortium— 8 ‘‘(A) shall include representatives of— 9 ‘‘(i) the institutions that are part of 10 the U01 Trial Readiness Project of the 11 National Institutes of Health, or that are 12 part of other nationally recognized clinical 13 Centers of Excellence; and 14 ‘‘(ii) at least 1 national CCM patient 15 advocacy organization, which may be an 16 entity that receives a grant or contract 17 under subsection (b)(2)(A); and 18 ‘‘(B) may include representatives of the 19 National Institutes of Health or the Food and 20 Drug Administration, in an advisory or ex offi- 21 cio role. 22 ‘‘(3) RESPONSIBILITIES.—Through a con- 23 sensus-based decision-making model, the consortium 24 shall divide assignments and be responsible for— 25 VerDate Sep 11 2014 01:12 Mar 08, 2023 Jkt 039200 PO 00000 Frm 00012 Fmt 6652 Sfmt 6201 E:\BILLS\S543.IS S543 kjohnson on DSK79L0C42PROD with BILLS 13 •S 543 IS ‘‘(A) developing and implementing training 1 programs for clinicians and scientists in accord- 2 ance with paragraph (4); 3 ‘‘(B) developing patient education, out- 4 reach, and awareness programs and materials, 5 which may be tailored for specific regional or 6 local needs including— 7 ‘‘(i) a regional multimedia public 8 awareness campaign; 9 ‘‘(ii) patient education materials for 10 distribution by regional physician and sur- 11 geon offices; 12 ‘‘(iii) an education program for ele- 13 [Text truncated for display. 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