Lead Neurotoxicity: Intervention/Prevention

January 22, 2007

Lead Neurotoxicity: Intervention/Prevention

Joseph Graziano, PhD Associate Dean for Research

Professor of Environmental Health Sciences and Pharmacology

Mailman School of Public Health Columbia University

January 22, 2007

1

2

3

4

5

6

7

8

The Development of DMSA (Succimer) as a Treatment for Childhood Lead Poisoning

• 1974: Animal model of Pb poisoning developed; begin screening candidate drugs

• 1977: DMSA identified as a potential antidote for Pb in an animal model

• 1982: Clinical trials begin at Columbia Univ. • 1990: New Drug Application submitted • 1991: FDA approval for use in children • SEVENTEEN YEARS! • What could have expedited this process?

What Could Have Expedited This Process?

• Higher throughput drug screening models

• Help in partnering with a pharmaceutical firm interested in an orphan drug

• The development of a network of sites involved in studies of children’s environmental health, with access to potential study participants

• Funding for additional clinical trial sites

9

10

11

1985 CDC guidelines

12

Blood Lead Levels in the U.S. Population 1976–1999

Blo

od L

ead

Lev

els (

mg/

dL)

18

16

14

12

10

8

6

4

2

lead NHANES II, III, 99+paintBan can solder 1976 phase-out

Begins unleaded 1978 gasoline

Introduced 1979 lead &

copperRule can 1991 solder

ends leaded 1992 gas

ends 1996

2.7 2.0

0 1974 1976 1978 1980 1982 1984 1986 1988 1990 1992 1994 1996 1998 2000

Year

Number 19May 10, 2001Volume 344:1421-1426

13

Thank You!

14

15

16

17

002t~~/23M~IO 'f'Nr; J~/llJ.L Otf)j.d.MJ.(:01.0(;t Al"D £xpt:a1~blt.-.I. 'T\ttaAnt1nca \'atm,NO.s CoPrrilhtC>l!l&5b,-'llw ~ricariSocitty Corf>ti.~-.nd~ri!DenuJTber~ ~£1\.U.$.A,

Use pf 2,3-Dimercaptopropane-1-Sulfonate in Treatment of Lead Poisoning in Children 1

J. J. CHISOLM, JR. and DAVID J. THOMAS

The. Kennedy Institute 10< Handicapped Children and the ...,.,,....... ,,,...,,., ..,.. , ....,._. - · ..................... ,.,.....,,_ ..... , ,..., -··~ • ~N v1 H,.11',,,,,, BaNUnote, Maryland

A<:cepted for publication Septe<rl>e< 16, 1985

ABSTRACT 2,3-0imercaptoproj)ane-1-suttooate (DMPS} is a wafer-soluble by DMPS administration and these increases were sustained metal complexing agent. Administration to lead-poisoned roil- throughout the 5-day course or treatment. No significant chMges dren or 5-day courses or 200 or 400 mg or DMPS per rrf surtace In hepatic, renal or hemaJOIOgical function were IOl.Wld in DMPS-area per day given p.o. in divided doses resulted in a significant treated children and no side effects attributable to DMPS were dedine in the concentration of lead in blood. DMPS treatment noted. II is c:onduded that a 5-day course of DMPS given p.o. did not significantly alter the concentrations or Uic or copper in may be sale and effective in the treatment or asymptomatic lead plasma. Uinaryexa-etion or lead, Uicand copper was increased poisoning in c:hidren.

CLINICAL TOXICOLOGY. 30(4), 493-504 (1992)

BAL, EDT A, DMSA AND DMPS JN THE TREI\. TMENT OF LEAD POISONING JN CIDLDREN

J. Julian Chisolm, Jr., M.D.

Lead Poisoning Program, Kennedy Institute Baltimore, Maryland