RESEARCH: ALS treatments

[Guest guest]

Two articles have appeared recently concerning

treatments for ALS--using a growth factor and a

cannabinoid. Both approaches showed some benefit.

Mark

VEGF delivery with retrogradely transported

lentivector prolongs survival in a mouse ALS model.

Azzouz M, Ralph GS, Storkebaum E, Walmsley LE,

Mitrophanous KA, Kingsman SM, Carmeliet P, Mazarakis

ND.

Oxford BioMedica plc, The Oxford Science Park, Medawar

Centre, Oxford OX4 4GA, UK.

Amyotrophic lateral sclerosis (ALS) causes

adult-onset, progressive motor neuron degeneration in

the brain and spinal cord, resulting in paralysis and

death three to five years after onset in most

patients. ALS is still incurable, in part because its

complex aetiology remains insufficiently understood.

Recent reports have indicated that reduced levels of

vascular endothelial growth factor (VEGF), which is

essential in angiogenesis and has also been implicated

in neuroprotection, predispose mice and humans to ALS.

However, the therapeutic potential of VEGF for the

treatment of ALS has not previously been assessed.

Here we report that a single injection of a

VEGF-expressing lentiviral vector into various muscles

delayed onset and slowed progression of ALS in mice

engineered to overexpress the gene coding for the

mutated G93A form of the superoxide dismutase-1

(SOD1(G93A)) (refs 7-10), even when treatment was only

initiated at the onset of paralysis. VEGF treatment

increased the life expectancy of ALS mice by 30 per

cent without causing toxic side effects, thereby

achieving one of the most effective therapies reported

in the field so far.

SOURCE: Nature. 2004 May 27;429(6990):413-7.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve & db=PubMed & list_uids=1\

5164063 & dopt=Abstract

____________________________________________

Amyotrophic lateral sclerosis: delayed disease

progression in mice by treatment with a cannabinoid.

Raman C, McAllister SD, Rizvi G, Patel SG, DH,

Abood ME.

Forbes Norris MDA/ALS Research Center, 2351 Clay

Street, Suite 416, California Pacific Medical Center,

San Francisco, CA 94115, USA.

Effective treatment for amyotrophic lateral sclerosis

(ALS) remains elusive. Two of the primary hypotheses

underlying motor neuron vulnerability are

susceptibility to excitotoxicity and oxidative damage.

There is rapidly emerging evidence that the

cannabinoid receptor system has the potential to

reduce both excitotoxic and oxidative cell damage.

Here we report that treatment with

Delta(9)-tetrahydrocannabinol (Delta(9)-THC) was

effective if administered either before or after onset

of signs in the ALS mouse model (hSOD(G93A) transgenic

mice). Administration at the onset of tremors delayed

motor impairment and prolonged survival in

Delta(9)-THC treated mice when compared to vehicle

controls. In addition, we present an improved method

for the analysis of disease progression in the ALS

mouse model. This logistic model provides an estimate

of the age at which muscle endurance has declined by

50% with much greater accuracy than could be attained

for any other measure of decline. In vitro,

Delta(9)-THC was extremely effective at reducing

oxidative damage in spinal cord cultures.

Additionally, Delta(9)-THC is anti-excitotoxic in

vitro. These cellular mechanisms may underlie the

presumed neuroprotective effect in ALS. As

Delta(9)-THC is well tolerated, it and other

cannabinoids may prove to be novel therapeutic targets

for the treatment of ALS.

SOURCE: Amyotroph Lateral Scler Other Motor Neuron

Disord. 2004 Mar;5(1):33-9.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve & db=PubMed & list_uids=1\

5204022 & dopt=Abstract