Stem Cell Therapy for Acquired Hearing Loss in Children; FDA-Approved Study. Linda Baumgartner, CCC-SLP, Cert.AVT James Baumgartner, MD

Transcription

1 Stem Cell Therapy for Acquired Hearing Loss in Children; FDA-Approved Study Linda Baumgartner, CCC-SLP, Cert.AVT James Baumgartner, MD

2 Stem Cell Basics I'll never grow up, never grow up, never grow up Not me, Not I, Not me! So there!

3 Stem Cell Basics Our Study uses ONLY Adult stem cells. Our Study uses ONLY Autologous stem cells. Avoids immune system issues We will now provide an overview of the types of stem cells currently being studied.

4 Stem Cell Basics Most cells divide symmetrically, producing two identical daughter cells Stem Cells are able to divide asymmetrically to form: More Stem Cells: Self Renewal Specialized Cells: Multi-Potency

5 Stem Cell Basics Stem Cell classification follows development: Totipotent, Pluripotent, Multipotent Stem Cell sources: Embryonic SCNT: Somatic Cell Nuclear Transfer IPSC : Induced Pluripotent Stem Cells Fetal Umbilical Cord Adult

6 Basic Embryology Three layers of the basic embryo Ectoderm Mesoderm Ectoderm Stem cells from a particular layer can only differentiate into the tissue types which typically form from that layer.

7

8 Stem Cells: Embryology 1

9 Stem Cell Embryology 2

10 Stem Cells: Umbilical Cord The umbilical cord is a rich source of multipotent adult stem cells Hematopoetic stem cells which generate blood cell lines and Mesenchymal stem cells Used in animals to treat strokes And to create chimeric animals to treat genetic diseases

11 Adult Stem Cells from Bone Marrow (Mesodermal)

12 Stem Cells: What s the Big Deal? Why are scientists so worked up over stem cells? Stem cells provide the potential to revolutionize treatments of various diseases Organ repair: traumatic brain injury, end stage heart disease, diabetes, stroke Stem cells have also provided improved understanding of the pathophysiology of some illness: Brain tumors. Have provided a window into the biology of the early stages of human development.

13 Stem Cells: Big Deal 2 Why are some people so worked up about stem cells? Equate stem cell isolation from frozen embryos with abortion because an embryo is destroyed life begins at conception They equate SCNT with cloning and abortion it is both the creation and destruction of life Tom Delay We have been Vatican Approved

14 Stem Cell Debate Many people participating in the stem cell debate are uninformed Confusion This confusion has paralyzed legislation on this subject in many states We are not advancing as fast as we should Please take the time to become informed, or stay out of the discussion.

15 Mechanism(s) of Action So we know where stem cells come from, how do they work? Two mechanisms: REGENERATIVE vs IMMUNOMODULATORY Regenerative: stem cells replace the missing/damaged cells (artificial trachea). Immunomodulatory: stem cells alter the immune response to injury in a way that allows intrinsic repair machinery to function better.

16 Immunomodulatory After an injury, the immune response kicks in. Sometimes this response is too strong: scorched earth Can make the injury more severe Can interfere with the body s ability to repair itself By altering and reducing the immune response, stem cell therapy can make the injury less severe, and allow for more complete recovery.

17 The Neuro-Immune Response

18 Motivating Case The animal data is compelling, but how do you know it will work in people? Compassionate Use Protocols Designed to use novel treatments in desperate cases Not particularly useful to collect academic information Often difficult to interpret Exceptional results lead to more organized studies.

19

20 Spaghetti Conversation Pediatric Traumatic Brain Injury Trial, completed in 2010, showed encouraging results. Linda: What about the deaf kids?

21 The Inspiring Animal Model Cochlear Repair by Transplantation of Human Cord Blood CD133+ Cells to Nod-Scid Mice Made Deaf With Kanamycin and Noise Revoltella R, Papini S, Rosellini A, Michelini M, Franceschini V, Ciorba A, Bertolaso L, Magosso S, Hatzopoulos S, Lorito G, Giordano P, Simo E, Ognio E, Pili M, Saccard R, Urbani S, Jeffery R, Paulsom R, Martini A. Cell Transplantation. 2008; Vol 17, pp

22

23 Translational Research What is it? Taking a research idea out of the lab and taking it into the clinic/hospital Doing experiments on people!

24 Pilot Study A pilot study is essentially a smaller version of the research main study Our pilot study is also a safety trial

25 Safety Trial Also known as a Phase I Clinical Trial Enrolls only a small number of people to determine if the treatment is safe Phase II dose escalation study Phase III double blind, prospective, randomized study

26 FDA: IND Food and Drug Administration, aka the FDA Agency of the United States Department of Health and Human Services, one of the United States Federal executive departments Led by the Commissioner of Food and Drugs, appointed by the President with the advice and consent of the Senate Grants licenses to use investigational drugs, cells and devices (IND)

27 IRB Institutional Review Board (Committee for the Protection of Human Subjects) Oversee research involving humans by health care, academic, governmental and other agencies and organizations Exist to protect the safety, health and privacy of human research subjects

28 NIH National Institute of Health A part of the U.S. Department of Health and Human Services Is the nation s medical research agency Responsive to Congressional legislation that adjusts NIH's programs to meet changing research needs. Fund Phase 2 and Phase 3 but not Phase 1 Our study is listed on NIH.gov ClinicalTrials.gov Identifier: NCT

29 Safety of Autologous Human Cord Blood Mononuclear Fraction to Treat Acquired Hearing Loss in Children

30 Safety of Autologous Human Cord Blood Mononuclear Fraction to Treat Acquired Hearing Loss in Children

31 Safety of Autologous Human Cord Blood Mononuclear Fraction to Treat Acquired Hearing Loss in Children

32 Safety of Autologous Human Cord Blood Mononuclear Fraction to Treat Acquired Hearing Loss in Children purified mononuclear cell (MNC) fractions derived directly from whole blood, human umbilical cord blood, bone marrow, or from a number of leukocyte-rich products A number of techniques used

33 Safety of Autologous Human Cord Blood Mononuclear Fraction to Treat Acquired Hearing Loss in Children Moderate to Profound SN Hearing Loss Unilateral or Bilateral Loss 6 weeks to 18 months of age Wearing amplification to support listening and language development Parents enrolled in an education program Hearing begins in utero at approximately 7 months of gestation

34

35

36 New Study: Inclusion Criteria Genetic Testing or Known Cause of HL

37 Connexion 26 Mutations in the GJB2 gene are a major cause of prelingual non-syndromic deafness. This gene provides instructions for making a protein called connexin 26. The GJB6 gene also provides instructions for making a connexin protein, connexin 30. These proteins form parts (subunits) of channels called gap junctions, which allow communication between neighboring cells. Mutations in connexin proteins that make up gap junctions may affect the function or survival of cells that are needed for hearing. Reference: NIH.gov

38 Non-Syndromic Deafness Non-syndromic deafness is a condition related to changes in mitochondrial DNA. Mutations in the ACTG1, CDH23, CLDN14, COCH, COL11A2, DFNA5, DFNB31, DFNB59, ESPN, EYA4, GJB2, GJB6, KCNQ4, LHFPL5, MT-TS1, MYO15A, MYO6, MYO7A, OTOF, PCDH15, POU3F4, SLC26A4, STRC, TECTA, TMC1, TMIE, TMPRSS3, TRIOBP, USH1C, and WFS1 genes cause non-syndromic deafness- reference: NIH.gov

39 How will the baby s hearing loss be determined? The otoacoustic emissions (OAE) test shows whether parts of the ear respond properly to sound. The auditory brain stem response (ABR) test checks how the auditory brain stem and the brain respond to sound. Reference and additional information: National Institute on Deafness and other Communication Disorders (NIDCD)

40 New Study: Exclusion Criteria Syndrome Genetic Cause of HL More than 18 months past onset of HL Mild HL History of multiple ear infections Conductive HL Infection within 2 weeks of treatment

41 Patient Experience During the treatment visit, the child will undergo: Speech evaluation, Neurology exam, ABR, OAE, Audiogram (if age appropriate), & screening labs. The patient will be admitted and undergo MRI with DTI, then receive their own hucb through an IV. At one and three month follow-up visits, all diagnostic studies and exams will be repeated except for the MRI. At six months follow-up, all diagnostic studies and exams and an MRI will be repeated The MRI requires general anesthesia.

42 Hearing Study: SLP Testing Testing Pre, 1 month, 3 months, 6 months Rossetti Infant Toddler Scale Ling 6 Observe stage of auditory development Language Sample (20 minutes) Phonetic Inventory Preschool Language Scale- fourth edition

43

44 Quiz Questions

45 Thank You