Giuseppe Perrella vs Fred Gage in un dibattito a BM&L
La discussione a
commento del lavoro condotto dall’equipe di Fred Gage, pubblicata su questo
sito il 28 settembre scorso in “Note e Notizie” con il titolo:
“Vettori virali
nella terapia della Sclerosi Laterale Amiotrofica (SLA)”, ha determinato lo
sviluppo di un vivace dibattito tra i soci di BM&L. Il presidente della
Società Nazionale, condividendo e sostenendo l’opinione e l’angolazione critica
espressa dai neurobiologi nella nota che ha contribuito ad elaborare, ha
ulteriormente chiarito i termini del dibattito generale sulla ricerca, sul
rapporto dei ricercatori con le fonti di finanziamento e sui criteri di
valutazione dei protocolli e dei risultati.
Nel corso della sua
esposizione ha evidenziato come esistano dei rapporti politici di intesa fra
ricercatori, a tutela di interessi legati al proprio prestigio ed alla propria
carriera, che spesso entrano in aperto conflitto con la verità scientifica. Ad
esempio, ha mostrato il giudizio espresso per conto della Christopher Reeve
Paralysis Foundation (CRPF) da Susan Howley –che di seguito riportiamo-
direttore di ricerca e vice-presidente esecutivo dell’associazione che ha
finanziato con il Salk Institute il lavoro di Gage:
“This study is exciting from the perspective of spinal
cord injury, because it shows that the viral vector is a safe and effective
mechanism to deliver substances to the spinal cord. CRPF is pleased to have
provided partial underwriting for this study”, stated Susan Howley, Director of Research/ Executive Vice President,
CRPF.
Non
è necessario interpellare un premio Nobel, ha sostenuto il presidente, per
rendersi conto che questo lavoro non era un test di innocuità dei virus
adeno-associati, né si prefiggeva lo scopo di testare un meccanismo per inviare
sostanze al midollo spinale e, soprattutto, non aveva nessun diretto rapporto
con il danno traumatico che colpì Christopher Reeve e determinò la fondazione
dell’associazione stessa.
Ancora
più sconcertante –ha proseguito- è notare come per parte opposta il Salk
Institute presso il quale Gage lavora come professore di Genetica, non soltanto
presenta la ricerca come un lavoro di genetica (terapia genica) cosa senz’altro
più appropriata, ma si incarica di un servizio di propaganda nella migliore
tradizione dell’ufficio-stampa dei candidati alle elezioni presidenziali,
definendo “unique gene therapy method” la procedura seguita in un lavoro non
ancora bene sviluppato e non ancora pubblicato nella forma dell’articolo. Si
ricorda, infatti, che si trattava di un “report”.
Di
fatto l’articolo di propaganda (che riportiamo in calce alla nota),
assolutamente sproporzionato per quegli esperimenti, è stato redatto a cura
dello stesso Gage che fin dall’inizio e a più riprese sottolinea lo scopo di terapia
della SLA (in inglese ALS o Lou Gehrig Disease) in quanto la principale fonte
di finanziamento, dopo il Salk, è il “Project ALS”.
Visto
che gli altri enti che hanno finanziato la ricerca sono il “National
Institute on Aging” e il “National Institute of Neurological Diseases and
Stroke”, c’è da attendersi che gli uffici-stampa di questi istituti ci
comunichino che la ricerca di Gage consentirà anche di arrestare
l’invecchiamento e guarire ogni ictus.
Nicole Cardon per
BM&L-Settembre 2003
The Salk Institute
for Biological Studies today issued this press release on behalf of one of its
investigators, Fred Gage, Ph.D. Dr. Gage is a member of the CRPF Research
Consortium on Spinal Cord Injury.
Gene Therapy Postpones Lou Gehrig's Disease Symptoms
Retrograde Viral Delivery of IGF-1 Prolongs Survival
in a Mouse ALS Model, B. J. Kaspar, J. Lladó, N. Sherkat, J. D. Rothstein, F.
H. Gage, Science, Aug 8, 301, 839-843,
2003
La Jolla, Calif. -- A unique gene therapy method
postpones the symptoms and nearly doubles the life span in a mouse animal model
of Lou Gehrig's disease, a research team led by the Salk Institute has found.
The findings are the first to show this degree of recovery after the paralyzing
and ultimately fatal nervous system disorder begins and may lead eventually to
a new, gene-based treatment for the disease that affects more than 30,000
Americans. The study appears in the August 8 issue of the journal Science. Fred
H. Gage, professor of genetics, Salk research fellow Brian Kaspar, Jeffrey Rothstein,
professor of neurology at Johns Hopkins University, and their colleagues found
that injecting a gene that produces the nerve cell growth-stimulating protein,
insulin like growth factor-1 (IGF-1), into muscles resulted in longer life
spans, preserved nerve cells and reduced muscle wasting. Lou Gehrig's disease,
known as amyotrophic lateral sclerosis (ALS), is marked by the degradation of
nerve cells that control muscle movement. It quickly attacks these motor nerve
cells in the brain and spinal cord, resulting eventually in total paralysis and
death. Its cause is unknown. While the disease was first identified in the 19th
century, it gained international attention in 1939 when baseball great Lou
Gehrig announced he had ALS and retired from the New York Yankees. He died two
years later."IGF-1 protein has been used in clinical trials for a while,
with marginal results," said Gage. "The biggest challenge has been
to deliver the protein across the blood-brain barrier into the central
nervous system. By injecting our viral vector into muscles, the gene could then
deliver the protein into nerve cells that controlled the muscle, resulting in
the preservation of those nerve cells that would otherwise have succumbed more
quickly to ALS." "ALS is a terrible disease, and patients have few
choices for therapy today," said Rothstein, also professor of neuroscience
and director of the Robert Packard Center for ALS Research at Johns Hopkins.
"This animal study is the first to identify a treatment that slows the
disease once symptoms have already appeared, a significant finding that offers
insight into the disease mechanism and important therapeutic potential."
Gage and his colleagues found that delivery of a non-toxic gene therapy, using
an adeno-associated virus that carried IGF-1 into muscle (with subsequent
transfer of IGF-1 to neurons dying in ALS), delayed disease onset by 31 days
and expanded the mice's life span to a maximum of 265 days, compared to 140
days for the untreated mice.
IGF-1 was also able to extend life spans by 22 days when injected after
symptoms appeared, indicating the method's potential treatment for different
stages of disease. In addition to extending survival, treatment with the gene
therapy maintained physical movement for a significantly longer time than in
untreated mice and provided 20 percent more muscle mass. The researchers
demonstrated that IGF-1 triggers a molecular pathway that appears to preserve
motor nerve function. When the receptor for IGF-1 is activated, an enzyme
called Akt has a phosphate molecule added to it (a process called
phosphorylation). The Akt enzyme is activated and helps block the process of
apoptosis, or programmed cell death. "IGF-1 has been known to increase the
number of phosphorylated Akt molecules, which inhibits apoptosis by directly
inhibiting different pro-apoptotic signals," said Gage. "We found
that IGF-1 decreased levels of a specific protein involved in apoptosis by more
than 63 percent compared to untreated mice. Understanding this pathway led us
to experiment with IGF-1 in the first place, and underscores the vital
importance of understanding the fundamental mechanisms of cellular function to
medical advances." While this research is still in the experimental animal
stage and a number of steps need to be taken before any possible therapy is
deemed safe and effective enough for use, researchers are in the planning
stages of human trials for this gene therapy method.
This research was supported by grants from Project
ALS, Christopher Reeve Paralysis Foundation, the National Institute on Aging
and the National Institute of Neurological Diseases and Stroke.
The Salk Institute for Biological
Studies, located in La Jolla, Calif., is an independent non profit organization
dedicated to fundamental discoveries in the life sciences, the improvement of
human health and conditions, and the training of future generations of
researchers. Jonas Salk, M.D., founded the institute in 1960 with a gift of
land from the City of San Diego and the financial support of the March of Dimes
Birth Defects Foundation.
Copyright 2003 by Christopher Reeve Paralysis Foundation
500, Morris Avenue, Springfield NJ 07081. All Right Reserved