Unità di Neuropatologia Sperimentale

Istituto di Neurologia Sperimentale INSPEDivisione di Neuroscienze

Ospedale San RaffaeleDr. Angelo Quattrini

Lecce 21 gennaio 2015

Unità di Neuropatologia Sperimentale

Attività clinica: • Biopsia di nervo sensitivo• Biopsia di nervo motorio• Biopsia di cute

Attività di Ricerca:• Biomateriali per la rigenerazione del sistema

nervoso• Neuropatie periferiche e malattie del

motoneurone• Validazione di modelli sperimentali (SNC – SNP)

Biopsia Nervo Surale

Danno assonale

Biopsia Nervo Otturatorio

• 15 Patients: 9 MND and 6 MN

• MN: demyelination with small onion

bulb, clusters of regeneration

• MND: loss of fibers, acute fiber

degeneration, rarity of regenerative

clusters.

Usefulness of motor nerve biopsy: diagnostic validation

Case #3

Case #4 Case #7

Validate by two-year clinical follow up the diagnostic usefulness of

the motor nerve biopsy

21 patients (between 2003-2006) - Progressive muscular weakness and wasting of unknown

origin affecting more than one limb - onset extending 1 months or more - no signs of sensory

neuropathy - EMG features of neurogenic changes

Baseline: neuropathological diagnosis:

12 patients: MND (CD<20/mm2)

1 patient: not diagnostic

8 patients: MN

1: amyloid neuropathy (CD: 24/mm2)

4 signs of demyelination/remyelination

Follow-up: neuropathological diagnosis:

12 patients: MND

1 patient: MND

8 patients: MN/SMN

1: SM amyloid neuropathy

ALS

MN

Case 4: 58y/M

Symmetric

weaknes: LL>UL

D=P

Clinical follow-up:

ALS

MND: typical features. Axonal degeneration, no regeneration, focal/pathcy reduction of nerve fibres

Motor neuropathies: typical features

Case 16: 60y/M

Symmetric

weaknes: LL>UL

D=P

Clinical follow-up: SMN

Motor neuropathies: specific features. Amyloidosis

Case 14: 59y/M Asymmetric weakness:

LL>UL

D>P

Conclusions

• Biopsy of the motor nerve to the gracilis muscle is a simple procedure. It has an acceptably low complication rate.

• Motor nerve pathologic examination was helpful for early differential diagnosis of LMN syndromes

• Motor nerve biopsy should be considered as a potential diagnostic tool for early differential diagnosis of selected cases of LMND and MN

PNS Neuropathology: ALS animal model

ACUTE NEUROPATHY / NEURONOPATHY

Motor Compartment involvement

DORSAL ROOR GANGLION

VENTRAL ROOTMotor Compartment involvement

Exploring the peripheral nervous system path to unravel Amyotrophic Lateral sclerosis

Razionale: La degenerazione a carico dei nervi periferici è un evento precoce della malattia nonché una delle principali causa di debolezza muscolare.

Obiettivo: definire il ruolo del sistema nervoso periferico nell’evoluzione della SLA.

L’obiettivo sarà identificare nuovi marcatori diagnostici di malattia. Il desiderio è quello di individuare, inoltre, potenziali target terapeutici con lo scopo di proteggere le fibre dei nervi periferici dalla progressiva degenerazione e mantenere la forza muscolare nei pazienti affetti da SLA.

Foglio1

Pagina 1

Probe ID Gene Symbol

ILMN_1815556 PRAP1

ILMN_1792356 DPYSL4

ILMN_1705397 PDK2

ILMN_1767015 BCORL1

ILMN_2318568 HCFC1R1

ILMN_1741755 TRIM29

ILMN_1653927 SNORD83A

ILMN_1660501 LY6H

ILMN_1652147 MRPL43

ILMN_2237252 LY6H

ILMN_1661708 LGALS7

ILMN_1702009 SV2A

ILMN_2053992 HIST4H4

ILMN_1712913 UNC5A

ILMN_1701875 ZYX

ILMN_2052438 CYorf14

ILMN_1800843 SCAMP4

ILMN_2300695 IKZF3

ILMN_1674243 TFRC

ILMN_1675331 PEG3

ILMN_1695311 HLA-DMA

ILMN_1726327 AMY1B

ILMN_3310216 MIR1911

ILMN_2294762 AMY1A

ILMN_2213558 TMED10P

ILMN_1696035 C12orf8

ILMN_1739622 PPP1R12A

ILMN_2102515 PGAM4

ILMN_1777976 SLC25A26

ILMN_3243441 EEF1AL7

ILMN_1690894 TRA1P2

Up-regulated genes

Down-regulated

genes

Microarray Gene Expression

Drug Discovery

Neuropathological features of Metachromatic Leukodystrophy mice

Consiglio A. et al, Nat Med 2001;7:310-316

Correction of established neurological deficits.

The neurophysiological deficits were normalized in treated mice along with the major

histopathological abnormalities:

Consiglio A. et al, Nat Med 2001;7:310-316Biffi A. et al, J Clin Invest 2004;113:1118-1129Biffi A. et al, J Clin Invest. 2006;116:3070-3082

Animal experiments and human studies are complementary and both are necessary.

HSC gene therapy can prevent progression of MLD.