STOPprogression

PROTECT & REGROWremaining tissues

REPLACE damaged tissues

A Cure For WolframThree Steps 2.0

Fumi Urano, MD, PhD

1. Stop the progression

FDA-approved drugs

Novel drugs

Common Molecular Pathway

ER Calcium leakage

Identify FDA-approved DRUGS that can prevent ER calcium

depletion-mediated Cell Death

Urano F. Diabetes (2014)

Induced Pluripotent Stem Cells from Wolfram patients

Drug A prevents apoptosis in Wolfram iPSC-derived neuronal cells

Lu et al. unpublished

TREATMENT

High in Patients

Low in Non-Patients

Drug A in a mouse model of Wolfram

hippocampus cerebellum midbrain brain stem cortex0

0.5

1

1.5

2

2.5

3

con watercon danko waterko dan

1

23

2. Protect and Regrow remaining tissues

What is MANF? Purified from Brain

Promotes Cell Growth

Prevents Cell Death

Retinitis Pigmentosa

Parkison’s disease

MANF-based treatment

Eye cells derived from Wolfram iPS cells

MANF peptideFrom Amarantus

3. Replace the damaged tissues

REGENERATIVE MEDICINE

Brain Cells and Eye cells from skin cells

Skin fibroblasts

BRAIN

EYE

iPS Cells

Replace disease-causing DNA with the healthy one

L 1 2 3 4 5 6 7 8

Expected size 877bp

Expected size 1268bp

5’ 3’

STOPprogression

PROTECT & REGROWremaining tissues

REPLACE damaged tissues

A Cure For WolframThree Steps 2.0